International Journal of Applied Pharmaceutics

Abstract Book: Proceedings of 2nd International Conference on Modern Tools and Approaches in the Emerging Field of Pharmaceutical and Biomedical Research 20-22, Nov 2024

Abstract Book — 2024-11-13

Proceedings of 2^nd International Conference on Modern Tools and Approaches in the Emerging Field of Pharmaceutical and Biomedical Research 20-22, Nov 2024

FORMULATION AND OPTIMIZATION OF BUDESONIDE COLON-TARGETED TABLETS USING CONTROLLED POROSITY OSMOTIC PUMP TECHNOLOGY

VOLETI VIJAYA KUMAR — 2025-01-07

Objective: Formulation and optimization of Budesonide (BDU) controlled porosity osmotic pump tablets (CPOP) to treat Nocturnal Asthma (NA) by adopting the Quality by design approach was set as objective of this research work.

Methods: Solubility of Budesonide was enhanced by converting in to the form of BUD Solid dispersions, using poloxamer 188. Controlled Porosity Osmotic pump (CPOP) tablets of budesonide were formulated by wet granulation technique. Quality by design approach using Box-Behnken design was adopted to optimize the selected critical factors. The optimized formulation was compared with the marketed extended-release formulation.

Results: The percentage of drug released at 4 h (D4), 7 h (D7), and 10 h (D10) were identified as response factors during the optimization phase. Statistical analysis showed that a combination of 200 mg of the SPM coat, 19.72 mg of Eudragit S 100 for the enteric coating, and 69.74 mg of guar gum in the core could achieve drug release rates of 9.4% after 4 h, 55.9% after 7 h, and 96.6% after 10 h of administration for the CPOP tablets.

Conclusion: The results indicated that the CPOP tablets were successfully formulated for colon-targeted drug release.

PREVENTING DIABETIC KIDNEY DISEASE: A SYSTEMATIC REVIEW OF CURRENT PHARMACOLOGICAL APPROACHES

B. DHARANI — 2025-01-07

Objective: This review examines the growing global burden of Diabetic Nephropathy (DN), a major complication of Diabetes Mellitus (DM) and a leading cause of Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD). With diabetes rates increasing, DN presents a significant health challenge. Current treatments manage established DN, but preventive strategies targeting high-risk individuals are urgently needed. This review evaluates current and emerging therapies for DN prevention.

Methods: A comprehensive literature search was conducted across multiple databases (PubMed, Web of Science, SCOPUS and others) to identify studies on the treatment and prevention of DN in DM patients. Eligible studies included Randomized Controlled Trials (RCT), cohort studies and meta-analyses published upto 2024, focusing on outcomes like albuminuria, Glomerular Filtration Rate (GFR) and ESRD incidence.

Results: Current treatments, including Sodium Glucose Co-transporter 2 (SGLT2) inhibitors, Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blocker (ARB), effectively reduce albuminuria and slow progression. Emerging therapies, such as antioxidants (Alpha-Lipoic Acid (ALA), Resveratrol), Mineralocorticoid Receptor Antagonists (MRA) and Endothelin Receptor Antagonists (ERA), show promise in improving kidney function and reducing inflammation. Other potential therapies targeting Oxidative Stress (OS), inflammation and fibrosis, such as Advanced Glycation End products(AGE) inhibitors and Tumor Necrosis Factor-α (TNF-α) inhibitors, have demonstrated preclinical efficacy but require further validation.

Conclusion: While current therapies slow DN progression, they do not offer definitive prevention. Emerging treatments targeting oxidative stress, inflammation and fibrosis show promise in reducing kidney damage. However, challenges like side effects and long-term safety remain. Further research is needed to establish the efficacy of these therapies and develop personalized strategies for preventing DN in high-risk populations.

DESIGN AND DEVELOPMENT OF SOLID LIPID NANOPARTICLES CONTAINING ROSUVASTATIN USING CENTRAL COMPOSITE DESIGN

DISHARI DUTTA — 2025-01-07

Objective: Rosuvastatin calcium, a BCS class II drug with low solubility, was optimized using a central composite design to improve its bioavailability.

Methods: The study utilized Kolliphor RH 40 as an emulsifier and glyceryl monostearate as a solid lipid in preparing solid lipid nanoparticle dispersion, optimizing formulations based on mean dissolution time and entrapment efficiency.

Results: The study analyzed the entrapment efficiency and mean dissolution time of the prepared solid lipid nanoparticles. The range of mean dissolution time was found 7.1+0.5 to 8.9+0.6 h. The highest entrapment efficiency was found to be 90.28%, with a standard deviation of 0.2. The linear model was chosen based on data precision and trend, while the quadratic model was selected for mean dissolution time. The 3D view graph indicated the model/equation followed by the formulations. The optimized formulation had a particle size of 16.16+10 nm and particle size distribution index to 0.729+002, indicating high homogeneity. Transmission electron microscopy images and dynamic light scattering data were in correlation. XRD, DSC used to analyze the drug's transformation into amorphous form. The dissolution profile of different formulations was plotted, and the optimized formulation followed the Korsmeyer-Peppas model. FTIR showed drug peaks, indicating no interaction.

Conclusion: The study suggested that the bioavailability of rosuvastatin calcium can be enhanced through the preparation of solid lipid nanoparticles of smaller size and sustained release of rosuvastatin.

EXPLOITING THE DESIGN OF EXPERIMENTS FOR PREPARING EXTENDED-RELEASE DOSAGE FORM OF GLICLAZIDE USING THE HOT-MELT EXTRUSION TECHNIQUE

IBRAHIM HASHIM — 2025-01-07

Objective: Polyethylene Oxide (PEO) is an amphiphilic polymer available in various grades, allowing manipulation of drug release rates. This work hypothesized the attempt to combine Hot-Melt Extrusion (HME) and Design of Experiments (DoE) with mixtures of various PEO grades to efficiently produce a dosage form with tailored drug release.

Methods: MODDE software recommended sixteen runs. A D-optimal mixture design evaluated the effects of gliclazide, PEO 303, and PEO 205 on the release profile of extrudates containing, as well fixed amounts of Polyethylene Glycol (PEG) 8000 and Colloidal Silicon Dioxide (CSD). The formulations were extruded at a screw speed of 20 rpm using a vertical lab-scale single screw with four heating zones set at 85, 90, 90, and 95 °C. The most discriminative dissolution method was used to generate release profiles of extrudate containing 30 mg of the drug. Factors affecting the drug release rate at 1, 3, 4, and 6 h were identified and modeled.

Results: The goodness of fit (R²) and prediction (Q²) for release responses were 0.969 and 0.830 at 1 h, 0.983 and 0.760 at 3 h, 0.987 and 0.687 at 4 h, and 0.947 and 0.786 at 6 h, respectively. The optimal design space for PEO 303 as a release-retarding polymer and PEO 205 as a release modifier at each gliclazide level (10–30%) was successfully constructed by Response Surface Modeling (RSM).

Conclusion: This work produced an extended-release profile of gliclazide that mimics the innovator by leveraging HME and DoE.

FORMULATION DEVELOPMENT AND PHARMACOKINETIC STUDIES OF NIRMATRELVIR LOADED SOLID LIPID NANOPARTICLES USING BOX-BEHNKEN DESIGN

SRI REKHA M. — 2025-01-07

Objective: This study aims to develop a new lipid formulation known as Solid Lipid Nanoparticles (SLNs) to increase the oral bioavailability of Nirmatrelvir (NMT) by facilitating intestinal lymphatic transport. Nirmatrelvir is a crucial antiviral agent utilized for the treatment and prophylaxis of Coronavirus disease 2019 (COVID-19).

Methods: Nirmatrelvir loaded solid lipid nanoparticles (NMT-SLNs) were formulated using the microemulsion technique with compritol 888 ATO, and the optimization of lipid and surfactant concentrations, as well as homogenization time, was achieved through the box-behnken design. The resulting NMT-SLNs underwent evaluation for percentage entrapment efficiency, Particle diameter, Zeta potential, Polydispersity index (PDI), and In vitro drug release studies.

Results: Optimized formulation (NF8), yielded a particle of 183.26±2.12 nm size with a narrow distribution of 0.071±0.004PDI, negative zeta potential of-24.63±1.92 mV, percent entrapment of 86.94±2.08%, and cumulative drug release of 84.42±3.16% over 24 h. Furthermore, solid-state characterization by PXRD, surface morphology assessment by SEM, and an in vivo distribution study employing albino wistar rats were conducted. The findings demonstrated a 10.14-fold increase in relative bioavailability and an 85% enhancement in brain uptake compared to pure NMT solution following oral administration.

Conclusion: This research highlights the potential advantages of solid lipid nanoparticles (SLNs) in enhancing the oral delivery of nirmatrelvir. finally, the study concluded that SLNs serve as a promising vehicle for improving bioavailability and facilitating effective brain delivery.

FORMULATION AND EVALUATION OF AZELNIDIPINE FAST-DISSOLVING TABLETS

BALA HEMALATHA — 2025-01-07

Objective: The main aim of the present study was to improve the solubility and rate of dissolution of azelnidipine and thereby increase oral bioavailability. Azelnidipine is a calcium channel blocker that lowers blood pressure by relaxing blood vessels and relieving pressure on them. Azelnidipine is a Biopharmaceutics Classification System (BCS) class II drug with low bioavailability.

Methods: The present study involves the preparation and evaluation of solid dispersion of azelnidipine by physical mixing, fusion and solvent evaporation method using polyethylene glycol 6000 (PEG 6000) as a carrier. The prepared solid dispersions were evaluated for various parameters like angle of repose, carr’s index, particle size, drug content, Scanning Electron Microscopy (SEM) analysis, Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD) and in vitro dissolution studies. As part of the project, Microcrystalline Cellulose-Polyethylene Glycol (MCC-PEG) Conjugate, a novel superdisintegrant, was developed.

Results: Solid dispersions prepared by fusion (AF 6) in a drug-to-polymer ratio of 1:3 released 99.40% of the drug more quickly than pure drug and other dispersions. The optimized solid dispersion (AF6) was used to prepare fast-dissolving tablets of azelnidipine. In comparison to commercially available and alternative tablet formulations, the study suggests that azelnidipine tablets (AT 13), made with 5% microcrystalline cellulose-polyethylene glycol conjugate as a super disintegrant, exhibited rapid drug release of 99.92% in 15 min. The drug was released in the following order: MCC-PEG Conjugate>Crospovidone>Croscarmellose sodium>Sodium starch glycolate in all tablet preparations containing super disintegrants.

Conclusion: It can be inferred that MCC-PEG conjugate is an efficient super disintegrant by comparing its results with those of available commercial super disintegrants and caused the drug azelnidipine to release rapidly from fast-dissolving tablets.

DEVELOPMENT AND ASSESSMENT OF A SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM FOR ENHANCED SOLUBILITY OF DASATINIB

PRAGATHI DEVANAND BANGERA — 2025-01-07

Objective: The objective of this study was to increase the water solubility of Dasatinib (DAS) by incorporating it into a Self-Nano Emulsifying Drug Delivery System (SNEDDS). Dasatinib, a Biopharmaceutics classification system (BCS) class II drug, has poor solubility in aqueous media, affecting its oral bioavailability. Various oils, surfactants, and co-surfactants were chosen based on solubility tests, with the highest solubility selected.

Methods: Various compositions of oils, surfactants and co-surfactants with Smix concentrations as 1:1, 1:2 and 2:1 and there were 9 formulations under each of these groups with Oil: Smix concentrations of 1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2 and 9:1. Capmul MCM, Cremophor EL, and Tween 20 were selected as oil phase, surfactant, and co-surfactant, respectively. A pseudo-ternary phase diagram using the water titration technique optimized the nano-emulsification ratio. The optimized formulation was characterized and evaluated for thermodynamic stability, cloud point measurement, zeta potential, Poly dispersity Index (PDI), globule size, percent transmittance, robustness to dilution, and dissolution studies.

Results: Transmittance of 95% was demonstrated by the formulation, indicating transparency and stability. The zeta potential was over 30 mV, indicating strong electrical stability, and the average globule size was measured to be 85 nm. The formulation was shown to be stable at body temperature, as evidenced by the cloud point being reported above 95 °C. The formulation maintained its stability when diluted in water, 0.1N acid, and phosphate buffer. The formulation contained 85% of the dasatinib, according to the drug content study. The optimized SNEDDS formulation significantly increased drug release in in vitro drug release experiments as compared to the pure medication. The oral bioavailability of dasatinib in the SNEDDS formulation was shown to be 3.24 times higher than that of the pure medication, according to in vivo pharmacokinetic tests.

Conclusion: Consequently, the findings indicated that the formulation of dasatinib SNEDDS functions as a means of achieving increased drug loading, better dissolving profiles, and increased bioavailability for the BCS Class II drug dasatinib.

MOLECULAR DOCKING INSIGHTS INTO PROBIOTICS AS POTENTIAL INHIBITORS OF THE PI3K PATHWAY FOR COLON CANCER THERAPY

MOHD ABDUL BAQI — 2025-01-07

Objective: This study investigates the interactions of probiotics-derived bacteriocins with Phosphoinositide 3-kinases (PI3Ks), a key enzyme involved in cell growth and survival pathways, with a focus on the cancer-associated PI3K pathway (PDB ID: 1E8X). The aim is to explore the anti-cancer potential of these bacteriocins as inhibitors of the PI3K catalytic subunit.

Methods: Using the Glide module, the study first involved molecular docking of bacteriocins. Next, an Absorption, Distribution, Metabolism, and Excretion (ADME) study was conducted using Qikprop. The Prime Molecular Mechanics Generalised Born Surface Area (MM-GBSA) method was used to calculate binding free energy.

Results: Five bacteriocins demonstrated significant binding affinity and interactions, including hydrogen and hydrophobic bonds, with key residues such as Tyr867, Trp812, Asp950, Asn951, Lys802, Lys890, Lys833, Val882, Ser806, Thr886, and Gln893 in the PI3K catalytic subunit (PDB ID: 1E8X). Among these, Plantaricin D exhibited an excellent XP-docking score of-7.47 kcal/mol, indicating strong binding potential. Prime MM-GBSA analysis revealed promising binding affinities with ΔBind (-92.85 kcal/mol), ΔLipo (-65.81 kcal/mol), and ΔVdW (-47.34 kcal/mol). The ligand consistently interacted with residues Asp950, Lys890, Gln893, Ser894, Thr887, Ala885, Tyr757, Asp758, Lys802, and Val759.

Conclusion: Plantaricin D bacteriocin, characterized by functional groups including the primary amine (NH₂), carbonyl (C=O), hydroxide (OH), and oxygen (O), demonstrates significant potential as a PI3K inhibitor. This suggests its promising application as an anti-cancer agent, particularly for colon cancer.

OPTIMIZING ORAL BIOAVAILABILITY OF SUNITINIB: QUALITY BY DESIGN IN NANOBUBBLE FORMULATION

ANJANEYULU PATAMSETTI — 2025-01-07

Objective: The use of dextran nanobubbles is aimed at function as a delivery system for drugs like sunitinib. These specially designed nanobubbles enhance the drug's solubility, stability, and bioavailability, thus improving the therapeutic effectiveness. Moreover, they offer controlled release characteristics and can potentially enhance drug delivery to tissues or cells, thereby maximizing pharmacological results while reducing adverse effects.

Methods: Drug-loaded dextran nanobubbles were formulated using the emulsification technique and optimized using a Box Behnken design that considered process and formulation parameters. The Nanobubbles characterization includes Particle Size (PS), drug loading, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimeter (DSC), X-ray diffraction studies, stability studies, and as well in vitro and in vivo studies in rats.

Results: The optimized nanobubbles displayed a PS of 177.8±5.2 nm, zeta potential of-21.1±0.43 mV, and poly dispersity index of 0.262±0.089. With 69.12±1.41% of entrapment efficiency and 26.29±4.01% drug loading, in vitro studies revealed a superior drug release (99%) with ultrasound versus plain drug (39%). FTIR and DSC studies confirmed no drug-polymer interaction. Scanning electron microscopy images displayed uniform spherical nanosized particles. Stability studies indicated no significant changes after 30 days. The nanobubbles exhibited increased C_max (4.52) and AUC_0-t (5.27), promising enhanced solubility, absorption, and extended half-life.

Conclusion: The current investigation shows that dextran nanobubbles loaded with sunitinib have a promising delayed release potential, which makes them a possible treatment alternative for cancer.

MOLECULAR DOCKING INSIGHTS INTO PROBIOTICS SAKACIN P AND SAKACIN A AS POTENTIAL INHIBITORS OF THE COX-2 PATHWAY FOR COLON CANCER THERAPY

MOHD ABDUL BAQI — 2025-01-07

Objective: This study aims to explore the interactions between probiotics-derived bacteriocins and the COX (cyclooxygenase) pathway, particularly focusing on the cancer-associated COX-2 (cyclooxygenase-2) enzyme (PDB ID: 6COX). The goal is to assess the potential of these bacteriocins as inhibitors of COX-2, investigating their possible anti-cancer effects through modulation of this key enzyme involved in cell growth and survival pathways.

Methods: Using the Glide module, the study first involved the molecular docking of bacteriocins. Next, an Absorption, Distribution, Metabolism, and Excretion (ADME) study was conducted using Qikprop. The Prime Molecular Mechanics Generalised Born Surface Area (MM-GBSA) method was used to calculate binding free energy.

Results: Four bacteriocins demonstrated significant binding affinity and interactions, including hydrogen and hydrophobic bonds, with key residues such as Tyr385, Ser530, Tyr355, Arg120, Phe518, and Leu352, in the associated COX-2 enzyme(PDB ID: 6COX). Among these, Sakacin P exhibited an excellent XP-docking score of-6.73 kcal/mol, indicating strong binding potential. Prime MM-GBSA analysis revealed promising binding affinities with ΔBind (-90.85 kcal/mol), ΔLipo (-64.81 kcal/mol), and ΔVdW (-46.34 kcal/mol). The ligand consistently interacted with residues Tyr355, and Arg120.

Conclusion: Sakacin P bacteriocin, characterized by functional groups including the primary amine (NH₂), and oxygen (O), demonstrates significant potential as a COX-2 enzyme inhibitor. This suggests its promising application as an anti-cancer agent, particularly for colon cancer.

NETWORK PHARMACOLOGY BASED COMPUTATIONAL STUDY TO INVESTIGATE THE POTENTIAL MECHANISM OF SYZYGIUM CARYOPHYLLATUM AGAINST COLON CANCER

RAMADEVI PEMMEREDDY — 2025-01-07

Objective: Syzygium caryophyllatum, a traditional medicinal plant from the Myrtaceae family, is rich in potential phytoconstituents. Based on its ethnobotanical uses and documented pharmacological activities, present work was conducted to evaluate the probable mechanism of action of S. caryophyllatum to manage colon cancer by integrating network pharmacology and computational studies.

Methods: The plant extract was prepared by Soxhlet extraction method and in vitro screening was performed using Sulforhodamine (SRB) Assay on HT 29 cancer cell lines. We have used super-PRED database, Cytoscape network analyser tool, string database and CytoHubba for performing network analysis for the extract compounds reported in GC-MS analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and DAVID databases were used for gene set enrichment analysis. We have used Schrödinger suite Version 11.4's to perform computational studies.

Results: The extract has demonstrated significant in vitro cytotoxic activity (IC50 value is 49.01 µg/ml) and the GC-MS analysis identified seventy-six distinct compounds. The Gene Ontology (GO) and KEGG demonstrated that the shared targets were strongly associated with key processes involved in colon cancer. The current study has identified Estrogen Receptor Alpha (ESR1), Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1), Mitogen-activated protein kinase 3 (MAP3K), Epidermal Growth Factor Receptor (EGFR) and Signal transducer and activator of transcription 3 (STAT3) proteins as essential targets and 5,7-Dihydroxy-2-undecyl-4H-chromen-4-one, 7a,12-Dihydroindolo[2,3-a] quinolizine, 5-hydroxy-7-methoxy-2-methyl-8-(3-methylbutyl) chromen-4-one as key compounds. Docking studies of the compounds with core proteins completely supplemented their binding affinity and suggested strong interactions at the binding site.

Conclusion: These outcomes highlight the multi-target, multi-compound, and multi-pathway approaches of S. caryophyllatum against colon cancer.

DEVELOPMENT AND STABILITY EVALUATION OF ATORVASTATIN EXTEMPORANEOUS ORAL SUSPENSION FOR ELDERLY PATIENTS

SIRIKANYA KAEWPRADIT — 2025-01-07

Objective: This study aims to develop an extemporaneous oral suspension formulation of atorvastatin (ATV) and evaluate its stability.

Methods: ATV extemporaneous oral suspension was developed by preparation using different suspension vehicles. The developed formulation was stored at ambient temperature (30±2 °C) and refrigerated temperature (4±2 °C) to evaluate its physical and chemical stability. The formulation was also exposed to 3% hydrogen peroxide (H₂O₂), 1 M hydrochloric acid (HCl), and 1 M sodium hydroxide (NaOH) to evaluate its stability under stress conditions. ATV was analyzed using High-Performance Liquid Chromatography (HPLC), which was validated prior to use.

Results: A vehicle containing 0.6% sodium carboxymethyl cellulose (SCMC) was suitable for the preparation of ATV extemporaneous oral suspension. The HPLC method was found to have linearity covering the range of 10–100 mg/ml with a correlation coefficient (r) greater than 0.99. Accuracy and precision were in the range of 99–110% and below 11 %RSD, respectively. The pH and viscosity of the developed formulation stored under ambient and refrigerated temperatures did not differ over 7 d, while the re-dispersibility time of the formulation stored in refrigerator shifted to higher more slowly than the formulation stored at ambient temperature. The % ATV remaining over 7 d was 92.02–106.67% at 30±2 °C and 99.64–107.58% at 4±2 °C. After being subjected to stress conditions, ATV remained stable under oxidation and alkaline conditions, while it significantly degraded under acidic conditions, remaining 24.27%.

Conclusion: The developed ATV extemporaneous oral suspension using a suspension vehicle containing 0.6% SCMC was chemically stable for at least 7 d at 30±2 °C and 4±2 °C. However, this formulation should be preferably stored at refrigerator temperature for use within 7 d to maintain both chemical and physical stability. The formulation was not stable under acid-stress conditions.

DESIGN, DEVELOPMENT, AND CHARACTERIZATION OF CURCUMIN-LOADED NANO TABLET IN ENDOMETRIOSIS TREATMENT

UMMANGALBALAN ABHINI — 2025-01-07

Objective: The goal was to simplify the manufacture of curcumin-loaded-nanosponges (CUNS) and test their vaginal delivery of CU for endometriosis in mice.

Methods: The independent parameters of CU-β-Cyclodextrin (CU-β-CD) NS generation were improved using box-behnken design (BBD). BBD with three factors and three levels was used for the studies. The study used carbonyldiimidazole as a cross-linking agent and lyophilization to create CU-β-CDNS. The anti-endometriosis activity of nano-tablet was tested in mice with peritoneal endometriosis.

Results: The mean particle size was 76.78–154.56 nm, and the encapsulation effectiveness was 76.62–86.68%. Transmission Electron Microscopy showed that the polymer encapsulated CU. In vitro antioxidant activity showed that CU and CUNS had SC₅₀ values of 5243.52±389.92 and 187.36±16.78 μg/ml, respectively. Bio-adhesion studies showed hydroxypropyl methylcellulose and xanthan gum performed better. The F1 and F2 formulations had better in vitro drug release at 12 h, with values of 97.12±2.38 and 95.34±3.24%, respectively. Photostability and simulated intestinal fluid testing were good. Endometriosis mice had leukocyte infiltration and fibrosis, while control mice had increased stromal vessel density and intact epithelium. However, CU nanogel greatly alleviated these issues. Histopathology demonstrated CUNS-pill corrected endometrial pathology.

Conclusion: The study advised CUNS-pill for endometriosis treatment.

GC-MS ANALYSIS AND MOLECULAR DOCKING STUDIES OF Laserpitium LATIFOLIUM L EXTRACT FOR ANTI-DIABETIC ACTIVITY

DIVYA MUKKA — 2025-01-07

Objective: To assess the anti-diabetic activity of Lasterpitium latifolium l extract through computational docking studies.

Methods: Crude extract of Lasterpitium latifolium l whole plant was obtained using a rotary evaporator. The extract was analyzed for bioactive compounds using Gas chromatography/Mass spectrometry (GC-MS). The extract was examined for their anti-diabetic effects through computational docking studies and in vitro. For docking studies, proteins of diabetes mellitus, α-amylase and α-glucosidase, were selected from the literature.

Results: Binding affinity assessed by score function identified 2,4-Thiazolidinedione, 5-[[4-(4-pyridinyl)-6-quinolinyl] methylene]-(5Z)-(highest docking score of-7.8 kcal/mol) and cycloartenol acetate (docking score of-7.5kcal/mol) are the most promising compounds that showed strong affinity to target proteins of diabetes mellitus. These compounds have the highest docking scores, suggesting that they are potential candidates for anti-diabetic drug development. Extract of L. latifolium exhibited 68.1% potent activity at 250 μg/ml.

Conclusion: In the anti-diabetic potential of crude extracts, multiple pancreatic and extra-pancreatic mechanisms may occur synergistically to achieve a strong anti-diabetic effect.

EXPLORING JACKFRUIT FLOUR POLYPHENOLS AS PROMISING SGLT-2 INHIBITORS FOR HYPERGLYCEMIA MANAGEMENT

SHASHANK M. PATIL — 2025-01-07

Objective: This study explored the potential of dietary polyphenols from whole green jackfruit flour as natural Sodium-Glucose Co-Transporter-2 (SGLT-2) inhibitors for managing hyperglycemia in diabetes mellitus.

Methods: Advanced bio-computational techniques, including molecular docking, Molecular Dynamics (MD) simulations, and binding free energy calculations, were employed to identify and assess polyphenols from jackfruit flour. Caffeic and syringic acids were highlighted for their strong binding affinities to the SGLT-2 receptor. Additionally, a ligand-based pharmacophore model was developed using caffeic acid as a reference to screen for new lead compounds in commercial and natural product databases.

Results: The study found that caffeic acid and syringic acid exhibited stronger binding affinities and more stable interaction profiles with the SGLT-2 receptor than the standard drug empagliflozin. MD simulations demonstrated that these compounds provided greater stability in the binding site, indicating their potential efficacy as SGLT-2 inhibitors. The pharmacophore screening further supported these findings, identifying both compounds as promising lead candidates.

Among the 14 dietary polyphenols obtained from High-Performance Liquid Chromatography (HPLC), a molecular docking study suggested that caffeic acid (binding affinity:-9.0 kcal/mol) and syringic acid (binding affinity:-9.1 kcal/mol) exhibited stronger binding affinities and more stable interaction profiles with the SGLT-2 receptor compared to the standard drug empagliflozin (binding affinity:-10.4 kcal/mol). Further, molecular dynamics simulations demonstrated that these compounds provided greater stability in the binding site, indicating their potential efficacy as SGLT-2 inhibitors through Root mean Square Deviation (RMSD), Root mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and ligand hydrogen bonds. The pharmacophore screening further supported these findings, identifying both compounds as promising lead candidates.

Conclusion: This study is the first to identify caffeic acid and syringic acid from whole green jackfruit flour as effective SGLT-2 inhibitors. These natural compounds show significant potential as novel agents for managing hyperglycemia and diabetes mellitus. The findings support further exploration of plant-derived therapies in diabetes treatment.

NANOENCAPSULATION OF CHITOSAN-ETHANOL EXTRACT OF RED BULB LEAVES (ELEUTHERINE AMERICANA MERR.) USING THE IONIC GELATION METHOD

WINTARI TAURINA — 2025-01-07

Objective: The red bulb is an endemic plant of West Kalimantan with high antioxidant activity. However, it is precarious and easily damaged.

Methods: This research aims to formulate red bulb leaf extract into nanoparticles to protect it from degradation. The polymer used is chitosan with Na-TPP as a cross-linker. The study aims to determine the concentration of chitosan that can form red bulb leaf extract nanoparticles and to characterize the resulting particles. The nanoparticles were prepared using the ionic gelation method by mixing Na-TPP, extract, and chitosan (1:1:6) with a magnetic stirrer at 1500 rpm for 5 h. The nanoencapsulation of the ethanol extract of red bulb was evaluated for characteristics including particle size distribution, polydispersity index, zeta potential, particle morphology, and entrapment efficiency.

Results: The nanoparticle formulations were characterized, yielding particle sizes for F1, F2, and F3 of 265.1 nm, 271.7 nm, and 299.8 nm, respectively, with polydispersity index values of 0.177, 0.208, and 0.194, respectively. The zeta potential values obtained in this study for F1, F2, and F3 were 1.10 mV, 0.43 mV, and 0.31 mV, respectively. The percentage inhibition of the free nanoparticle extract for F1, F2, and F3 was 22.328%, 17.853%, and 15.768%, respectively. The % inhibition value of the free extract against DPPH from the research results was 22.328±0.794% for formula 1, 17.853±1.048% for formula 2, and 15.768±0.780% for formula 3. The formulation that produced the best characterization results was F3, with a particle size of 299.8 nm, a polydispersity index of 0.194, and a zeta potential of 0.31 mV, although the particle morphology was less spherical.

Conclusion: The formulation that produced the best characterization results was F3, with a particle size of 299.8 nm, a polydispersity index of 0.194, and a zeta potential of 0.31 mV, although the particle morphology was less spherical. The % inhibition value of the free extract against DPPH from the research results was 15.768±0.780% for formula 3.

ULTRA-FAST SYNTHESIS OF CURCUMIN-LOADED SILVER NANOPARTICLES: IMPROVED PHYSICOCHEMICAL PROPERTIES FOR DRUG DELIVERY

CHONG XUE LI — 2025-01-07

Objective: This study focused on the green synthesis of silver nanoparticles (AgNPs) using fresh garlic extract (Allium sativum-AS) as a reducing agent for the efficient delivery of curcumin (CuR), a natural anti-cancer agent used in breast cancer therapy.

Methods: The study began with the preparation of fresh AS, which was then mixed with silver nitrate (AgNO₃) solution and CuR solution under sunlight for the green synthesis of stable CuR-loaded nanoparticles (C-AgNPs). This method not only offered an eco-friendly approach to the synthesis of C-AgNPs but also highlighted the potential physicochemical characterization of AS and CuR in this context. Moreover, this study assesses the characteristics of the resulting C-AgNPs and conducts a comparative analysis with different formulations to evaluate their efficacy.

Results: The prepared C-AgNPs, characterized by Fourier-Transform Infrared Spectroscopy (FTIR), indicated that CuR, silver nitrate (AgNO₃), and AS extract were successfully incorporated, confirming the successful synthesis. The optimized preparation, referred to as AgNP1, demonstrated an entrapment efficacy of 74.24±5.87%, a drug loading of 95.99±7.81%, and a drug content of 96.11±7.82%. Additionally, the cumulative percentage of drug release was found to be 57.12±2.76% at 180 min. The drug was successfully loaded into the C-AgNPs, exhibiting physicochemical compatibility without any adverse chemical interactions with the additives used.

Conclusion: In conclusion, this study demonstrated that nanoparticle-based drug delivery systems offer a significant advancement over conventional therapies by providing controlled and efficient drug delivery, thereby improving therapeutic outcomes.

BIO ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF FLUPENTIXOL AND NORTRIPTYLINE HCL IN RAT PLASMA AND ITS PHARMACOKINETIC STUDIES BY LCMS

V. VISALAKSHAMMA — 2025-01-07

Objective: An easy, quick, precise, active and reproducible Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) technique was developed for the bio-analytical method of flupentixol and nortriptyline HCl using zuclopenthixol as Internal Standard (IS).

Methods: This article summarizes the recent progress on bio-analytical LC-MS/MS methods using Luna Phenyl Hexyl column (250x4.6 mm, 5µ) and organic mobile phase of Ammonium acetate pH-3.0/Formic acid and Acetonitrile in 70:30 v/v. 5 min of run time was used in the analysis.

Results: The calibration curve was linear in the range of 5.0ng/ml to 200.0ng/ml (r²= 0.99988±0.006) for nortriptyline HCl and 0.25ng/ml to 10.0ng/ml (r²=0.99972±0.007) for flupentixol. Matrix effect, recovery and stability results were within the acceptable limit. An electrospray ionization source was used to study of nortriptyline HCl, flupentixol at m/z 300.8471 →73.2501, m/z 435.5225→103.4247 and m/z 400.9657→142.0087 for zuclopenthixol were ion pairs of mass analysis.

Conclusion: The application denotes all the parameters of system suitability, specificity, linearity and accuracy are in good agreement with United States Food and Drug Administration (USFDA) guidelines and applied effectively for the investigation of pharmacokinetic studies in rat.

ADDITIVE CYTOTOXIC EFFECT OF CISPLATIN AND ANDROGRAPHIS PANICULATA EXTRACT THROUGH THE MODULATION OF APOPTOTIC MARKERS, CYCLIN-D AND VEGF EXPRESSIONS IN SKOV3 OVARIAN CANCER CELL LINE

FARA VITANTRI DIAH — 2025-01-07

Objective: This study aims to investigate the possibility of additive cytotoxic effects of cisplatin and Andrographis paniculate (Burm. f.) Nees(AP) via apoptotic, cell cycle and angiogenesis pathways.

Methods: CC50 cisplatin, AP and Andrographolide (AG) were determined by the cell viability of SKOV3 after its exposure to these substances. SKOV3 cells were then divided into 6 experimental groups: one negativecontrol group, one with CC50 cisplatin alone, and three where CC50 was combined with CC50 AP, ½CC50 AP, and 1.5CC50 AP, respectively. The additive cytotoxic effect of cisplatin with AP or AG was evaluated through the modulation of several pathways via qRT-PCR of their markers: apoptotic pathways indicated by Bax, BCL2, Caspase 3 and Caspase 9 expression; cell cycle indicated by Cyclin-D expression; angiogenesis pathways by VEGF expression.

Results: Cisplatin reduces cell viability to 54%, 37% when combined with AG, and 30%, 23% and 20% with ½CC50 AP, CC50 AP and 1.5CC50 AP, respectively. AG and AP extract decreases SKOV3 cell viability in a dose-dependent manner. Cisplatin combined with AP showed a statistically significant increase in BAX, Caspase 3, Caspase 9 expression and a decrease in BCL2, which indicated synergy in apoptotic pathways. The best result was seen in cisplatin combined with ½CC50 AP. A decrease in Cyclin D and VEGF was seen in all groups, the best seen in ½CC50 AP and CC50 AP, respectively, showing optimal cell cycle arrest and anti-angiogenesis properties when cisplatin is combined with AP extract.

Conclusion: Combining cisplatin with AP extract enhanced cell cycle arrest, apoptosis, and anti-angiogenesis properties.

DESIGN, OPTIMIZATION (23FACTORIAL DESIGN), AND EVALUATION OF CARVEDILOL FAST DISSOLVING TABLETS BY EMPLOYING SOURSOP STARCH AS A NEW NATURAL SUPERDISINTEGRANT

VASUDEVA REDDY MATTA — 2025-01-07

Objective: The study objective is to focus on the isolation of the Soursop Starch (SSS) from the fruit pulp of Annona muratica (Soursop) used as a natural super disintegrating agent in the carvedilol formulation of Fast-Dissolving Tablets (FDTs) using (2³) factorial design.

Methods: The SSS was isolated from the fruits of Annona muratica (Annonaceae family) by using sedimentation and centrifugation techniques. The physicochemical properties of the SSS were assessed. A direct compression method was employed to prepare Carvedilol Fast-Dissolving Tablets (C-FDTs). The factorial design was adopted at two levels (0 and 5 %) of superdisintegrant, and the dependent variables are SSS, psyllium husk, and Sodium Starch Glycolate (SSG). The Critical Quality Attributes (CQA) were measured for all eight formulations, including Disintegration Time (DT), Wetting Time (WT), % Drug Dissolved in 10 Min (PD10) and dissolution efficiency. The finished C-FDTs were evaluated for different test parameters like drug content, water absorption ratio, weight variation, hardness, dissolution, dissolution efficiency at 10 min, and stability studies for optimized formulation.

Results: The isolated SSS was found to be insoluble in water and other inorganic solvents, and its swelling index, viscosity, bulk density, and tapped density were found to be satisfactory. The critical quality attributes like DT (22±1.38 sec), WT (24±0.58 sec), and PD10 (99.05±0.21 %) were found to be satisfactory for the optimized formulation (F2). The dissolution efficiency (F2) at a 10 min time point was found to be 44 times higher than that of the F1 formulation.

Conclusion: C-FDTs were successfully designed and optimized by employing the SSS as a natural superdisintegrant which exhibited a better % of the drug release in 10 min with good DT, dissolution efficiency, and all other FDT characteristics.

CILNIDIPINE-LOADED TRANSDERMAL NANOEMULSION-BASED GEL: SYNTHESIS, OPTIMISATION, CHARACTERISATION, AND PHARMACOKINETIC EVALUATION

MAHESH T. GAIKWAD — 2025-01-07

Objective: The aim of the study was to enhance transdermal flux and bioavailability, thereby reforming the effectiveness of drug delivery by synthesising and characterising cilnidipine-loaded nanoemulsion-based gel.

Methods: The research was conducted with meticulous planning and execution. After preformulation studies, cilnidipine-loaded nanoemulsions were synthesised using probe sonication and optimised by a 2-factor central composite design. The optimised nanoemulsions were loaded in Carbopol 940 and HPMC K₄M gelling system. The optimised nanoemulsions were characterised for droplet size, zeta potential, viscosity, refractive index, pH and TEM, and cilnidipine-loaded nanoemulsion gels were characterised for clarity, homogeneity, consistency, spreadability, extrudability, pH, viscosity, in vitro diffusion study, dermal toxicity, and pharmacokinetic profiling. The process was accurately planned and accomplished at each step to ensure the precision and reliability of the results.

Results: The findings of this research are not just significant; they are groundbreaking. The steady-state flux values observed ranged from 35.71±1.27 µg/cm²/h to 107.7±2.04 µg/cm²/h for DOE_CiL_1 to 9 and 40.88±1.44 µg/cm²/h to 80.64±1.38 µg/cm²/h for NEn_CiL_GeL_1 to 4. These results underscore the diverse efficacy of different formulations in facilitating drug delivery through the skin. The pharmacokinetics profile of cilnidipine also showed remarkable changes. The C_max for the cilnidipine tablet was 332.3±14.2 ng/ml, whereas it significantly increased (p<0.05) to 593.00±24.8 ng/ml in the nanoemulsion gel, demonstrating a substantial enhancement in drug concentration. Additionally, the AUC_0-12 showed a significant (p<0.05) increase from 1279±34.1 ng/ml. h with the tablet to 1922.50±162.8 ng/ml. h with the nanoemulsion gel. The AUC_0-∞ also increased from 1395.5±156.7 ng/ml·h for the tablet to 1962.30±174.9 ng/ml. h for the nanoemulsion gel, further confirming the improved bioavailability of cilnidipine with the nanoemulsion gel. These significant bioavailability improvements cause excitement about the potential impact of this research, which could revolutionise transdermal drug delivery systems in the pharmaceutical business, leading to more effective and efficient drug delivery methods.

Conclusion: The results of this novel study are not only promising but also hold the potential to be transformative. The significant improvement in transdermal flux from the cilnidipine-loaded nanoemulsion gel reveals a substantial increase in the drug's bioavailability. This breakthrough could eliminate several drawbacks of cilnidipine, like first-pass fate and poor solubility, and provide a safer, more convenient delivery method for managing hypertension.

SILK FIBROIN-COATED MESOPOROUS SILICA NANOPARTICLES ENHANCE 6-THIOGUANINE DELIVERY AND CYTOTOXICITY IN BREAST CANCER CELLS

MOHAMMAD AMIN KABOLI — 2025-01-07

Objective: Breast cancer stands as the most prevalent form of cancer among women globally. Conventional chemotherapy, including the use of 6-Thioguanine (TG), often faces limitations such as poor drug solubility. In this research, we engineered a nanosystem consisting of Mesoporous Silica Nanoparticles (MSNs) loaded with TG and coated with Silk Fibroin (SF) to enhance the pharmacokinetic properties of this drug in targeting the MCF-7 breast cancer cell line.

Methods: In this study, we investigated the cytotoxicity of different formulations through MTT assay. Additionally, we analyze apoptosis and cell cycle phase distribution using flow cytometry. Furthermore, the absorption of MSN nanoparticles by MCF-7 cells was investigated using the fluorescent labeling technique by Dil fluorochrome.

Results: Our results represented the 48 h Half Maximal Inhibitory Concentration (IC₅₀) values of free TG, MSNs loaded with TG (TG@MSNs) and SF-coated MSNs loaded with TG (SF/TG@MSN) were 16.69, 10.96 and 8.01 μM, respectively. Moreover, the percentage of total early and late apoptosis differed among the treatments. Specifically, cells treated with free TG, TG@MSN and SF/TG@MSN exhibited 13.49%, 76.05% and 84.99% apoptosis, respectively. The results also indicated that administering free TG and TG-loaded MSN nanoparticles to MCF-7 cells resulted in cell cycle arrest at the G2/M phase after 48 h of treatment.

Conclusion: Our study demonstrated that the SF/TG@MSN nanosystems effectively increased the cytotoxic effects of TG on the breast cancer cell line.

GREEN SYNTHESIZED ZNO NANOPARTICLES WITH CORDYCEPS MILITARIS FUNGUS EXTRACT FOR THE TREATMENT OF MEMORY IMPAIRMENT IN ALZHIEMER DISEASE

KHYATI SAINI — 2025-01-07

Objective: Preparation of Zinc Oxide (ZnO) Nanoparticles (ZnNPs) by green synthesis process using Cordyceps militaris fungus extract and its assessment for the treatment of Alzheimer’s disease.

Methods: ZnO nanoparticles were synthesized using the green synthesis process with Cordyceps militaris fungus extract. The nanoparticles were characterized using various techniques, including SEM, TEM, XRD, EDAX, and optimization techniques to determine their shape, size, surface properties, and crystallinity.

Result: The results showed that the nanoparticles were spherical with a smooth surface, averaging 37.09 nm in size, and exhibited surface Plasmon Resonance at 300 nm. XRD analysis confirmed their crystalline structure. During synthesis, the suspension changed from dark yellow to colorless with cloudiness, indicating nanoparticle formation. The UV-Visible Spectroscopy revealed a SPR peak at 375 nm. Overall, the characterization confirmed the successful synthesis of zinc nanoparticles with desired properties. This study investigated the protective effects of green-synthesized Zinc nanoparticles on memory impairment in mice. Mice were divided into six groups and treated with various substances followed by sleep deprivation to induce memory impairment. Conclusion: Behavioral tests and biochemical analysis revealed the significantly improved cognitive function, reduced acetyl cholinesterase activity in a dose-dependent manner, comparable to Donepezil. Histopathological analysis confirmed the protective effects of Cordyceps militaris against memory impairment.

EXPLORING NEW MONOAMINO OXIDASE- A (MAO-A) SELECTIVE INHIBITORS FROM CUCURBITO PEPO: A VIRTUAL SCREENING, MOLECULAR DOCKING, MD SIMULATIONS AND ADMET ANALYSIS

MAHENDRA GOWDRU SRINIVASA — 2025-01-07

Objective: This study aimed to identify potential Monoamine oxidase (MAO) inhibitors from Cucurbita pepo to address the increasing prevalence of neurological and neuropsychiatric disorders, such as stroke, Alzheimer's, Parkinson's, autism, migraines, and depression, by targeting key enzymes involved in neurotransmitter degradation.

Methods: The study utilised molecular docking and pharmacological, physiological, and ADMET property analyses to screen compounds from Cucurbita pepo. Ten promising MAO inhibitors were shortlisted for further analysis. Extensive Molecular Dynamics (MD) simulations were conducted over 100 nanoseconds to assess the stability and dynamic behaviour within the MAO-A complex.

Results: Based on molecular docking results, four shortlisted compounds were identified as potential MAO-A inhibitors. Atomic-level docking studies were used to explore the binding mechanisms of the phytoconstituents within the active site of the MAO-A enzyme. The binding free energies of these compounds ranged from-9.183 to-6.001 kcal/mol. Phytoconstituent Compound C1 had the highest binding affinity with a G score of-9.183 kcal/mol, followed by Compound C2 with a G score of-9.045 kcal/mol. MD simulations further confirmed that both C1 and C2 formed highly stable complexes with MAO-A, suggesting their potential as effective inhibitors.

Conclusion: Compounds C1 and C2 from Cucurbita pepo show promise as stable and effective MAO-A inhibitors. Further experimental validation is required to confirm these findings and evaluate their therapeutic potential in treating neurological disorders.

PREPARATION AND EVALUATION OF ENTRECTINIB PLGA NANOBUBBLES BY CENTRAL COMPOSITE DESIGN

P. NANDINI — 2025-01-07

Objective: For targeted delivery of entrectinib, we created nanobubbles with a poly(lactic-co-glycolic acid) (PLGA) shell and a perfluoropentane core.

Methods: Entrectinib was encapsulated in PLGA nanobubbles by a modified W/O/W double emulsion, solvent-diffusion-evaporation technique. Central composite design was utilized to explore how four independent factors like sonication distance (X1), amplitude (X2), time (X3), and power (X4)-affected droplet size (Y1) and polydispersity Index (PDI) (Y2).

Results: The optimal sonication distance, time, amplitude, and power were 2.41 cm; 3.61 min, 44.42%, and 77.35 W. Drug-loaded nanobubbles showed a PDI of 0.196±0.005 and an average particle size of 73.53±3.08 nm, indicating a unimodal system with low PDI high zeta potential indicate formulation stability. The mean drug loading capacity was 29.27±1.54 mg/g. The remarkable drug encapsulation efficiency (82.12±2.98%) supports an inclusion complex. Transmission Electron Microscopy shows drug encapsulation does not change nanobubbles' spherical shape. Fourier-transform infrared spectroscopy and Differential scanning calorimetry revealed nanobubble-drug complex production. Nanobubbles emitted more entrectinib than the solution. Drug release via ultrasound was different. At 6 h, sonication released 46.08% of entrectinib and 26.42% without. Entrectinib released 99.34% after 24 h versus 58.93% without ultrasonography. The formulation's consistent size distribution remained stable after 180 days. Parenteral safety and non-toxicity were shown by these nanobubbles at 15 mg/ml. In vitro ultrasonic increases cell uptake. The viability of MCF-7 cells was assessed following exposure to entrectinib at 10 to 120 μM dosages. All entrectinib formulations showed little cytotoxicity, up to 98% cell survival at 10 μM doses.

Conclusion: PLGA nanobubbles can be used in ultrasound-responsive formulations to deliver targeted drugs to fight cancer and other diseases.

FORMULATION AND EVALUATION OF AN ORAL TIMED PULSATILE DRUG DELIVERY FOR ALLEVIATING PAIN IN RHEUMATOID ARTHRITIS

PASAM JYOTHIRMAYI — 2025-01-07

Objective: The present study was aimed to formulate and evaluate an oral timed-release pulsatile drug delivery of AcecloFenac (AF) for rheumatoid arthritis pain by the Chronopharmaceutical approach with early morning breakthrough of AF as analgesic and anti-inflammatory agent for the treatment of rheumatoid arthritis.

Methods: A solubility was enhanced by formulating it as a self-emulsified system with a suitable oil and surfactant mixture. The interaction between the drug and the excipient was examined using Fourier Transform Infra-Red (FTIR) spectroscopy. The prepared formulation consists of 2 different parts: The basic design consists of burst-release core tablets with solid self-emulsified AF by using different super disintegrants, and the press-coating of optimised tablets by using different compositions of Ethylcellulose (hydrophobic) and Hydroxy Propyl Methyl Cellulose (HPMC K100) (hydrophilic) polymers.

Results: FTIR studies revealed no interaction between drug and excipients. From the solubility data, suitable oil and surfactants were selected. Pseudo-ternary plots help in finding of suitable surfactant mixtures for solid self-emulsified AF. Core tablets were evaluated for pre-compression characteristics, disintegration time, drug content, weight variation, hardness, friability, thickness, and % drug release. Among all solid self-emulsified formulations, S1C6 is successful, with 98.88% drug release in 20 min. The compression coat formulations were also evaluated for Hardness, weight variation, thickness, lag time, and in vitro drug release profile. Among them, F4 was optimised by its suitable lag time and drug release of 97.23% at the end of 6 h.

Conclusion: The system released the drug after a predetermined lag time of 4 h and thus, the dosage form can be taken at bedtime so that the drug will be released when the symptoms are prominent. Nine formulations were prepared, of which F4 formulation showed the highest drug release of 97.23 % at the end of 6 h and showed compliance with the chronotherapeutic objective of rheumatoid arthritis.

QUALITY ASSESSMENT OF VARIOUS BRANDS OF CEFIXIME 400 MG CAPSULES AVAILABLE IN YEMENI MARKET

AHMED M. AL-GHANI — 2025-01-07

Objective: The study aimed to assess the quality control of different brands of cefixime 400 mg capsule brands available in Yemeni drug market.

Methods: The pharmacopeial specifications of five cefixime 400 mg capsule brands available in Yemeni drug market, including two domestic brands, were assessed in this study. Assessment included assay content, capsule weight variation and disintegration. In addition, drug dissolution and antimicrobial activity test were assessed.

Results: Out of five brands, three brands of cefixime 400 mg capsules passed official specified assay tests according to United States Pharmacopeia (USP) specifications. The five brands showed a similar profile of weight variation and drug disintegration that were within the limits. However, the results of drug content for five brands showed in range 78.78-104.46 % in which three brands (B, D and E) in compliance to USP specifications (90-110%) and two brands (A and C) not compliance to USP specification. Also, the results of dissolution profile were in range 86.2-109.8% for four brands (A, B, D and E) that compliance to USP specifications, and 73.56% for brand C that was not compliance to USP specifications.

Conclusion: Based on the results obtained in this study, the drug content for three brands (B, D, E) is within the pharmacopeial limit, but the drug content of (A, C) is out of the limit. while the capsule disintegration, weight variations, and antibacterial activity in all tested brands are within the pharmacopeial limit. The dissolution profile for four brands (A, B, D, E) is within the pharmacopeial limit, but the dissolution profile for (C) is less than the allowed limit.

COMPUTATIONAL QSAR-BASED MACHINE LEARNING APPROACH FOR PREDICTING ACTIVITY OF SGLT2 INHIBITORS USING THE KNIME PLATFORM

ADHA DASTU ILLAHI — 2025-01-07

Objective: This study aims to identify optimal predictive models and key molecular fragments by preparing a dataset and using machine learning techniques within the Konstanz Information Miner (KNIME) platform.

Methods: The human Sodium-glucose Cotransporter 2 (SGLT2) target dataset was obtained from the ChEMBL database and refined by removing salts, incomplete/incorrect data, and duplicates. The data was classified into active and inactive compounds, and fingerprints and descriptors were calculated. Christian Borgelt's Molecular Substructure Miner (MoSS) was employed to identify frequent molecular fragments. Following data partitioning, various ‘classification’ and ‘regression’ machine learning (ML) based Quantitative Structure-Activity Relationship (QSAR) models were developed and evaluated using different techniques, including sensitivity and Mean Squared Error (MSE).

Results: In QSAR classification, the Support Vector Machine (SVM) model demonstrated the best performance with an accuracy of 81.66%, while in QSAR Regression, the Extreme Gradient Boosting (XGB) model exhibited the best coefficient of determination (R²) and Mean Absolute Error (MAE) values of 0.69 and 0.47 respectively. The identification of frequent Molecular Fragments highlighted common characteristics in active SGLT2 inhibitors.

Conclusion: The results of developing these QSAR models indicate that machine learning methods can be effectively used to predict SGLT2 inhibitors virtually, thereby expediting the drug discovery process.

FORMULATION AND EVALUATION OF ECONAZOLE NITRATE NANOEMULSION FOR TOPICAL OCULAR ADMINISTRATION

NANDHA KUMAR J. — 2025-01-07

Objective: The study aimed to use cold homogenization to create an Econazole Nitrate (ECN) nano-emulsion formulation.

Methods: Different ratios of surfactants (polypropylene 188 and Tween 80) and co-surfactants (ethanol) were used to create eight formulations. Out of them, compositions ECN1, ECN4, ECN5, and ECN7 were chosen due to initial research demonstrating encouraging outcomes. Dissolution studies evaluated droplet size, shape, drug content, and in vitro drug release characteristics. A comparative analysis was conducted to assess the improvement in medication release rates compared to pure drug formulations.

Results: ECN5, which attained an 89.43% drug release rate after 360 min, demonstrated the greatest medication release rate among the chosen formulations (ECN1, ECN4, ECN5, and ECN7). The improved formulations showed consistent spherical forms with droplet diameters ranging from 114 nm to 214.87 nm. Based on these findings, it appears that the nano-emulsion formulation successfully raises econazole nitrate's solubility, which is important because of its poor solubility in ocular administration applications.

Conclusion: The study used cold homogenization to effectively generate and optimize ECN nano-emulsion formulations. The most promising features of formulation ECN5, such as consistent droplet size distribution and dramatically improved drug release rates, were displayed. These results demonstrate the potential of nano-emulsions to enhance econazole nitrate's solubility and delivery effectiveness, especially for ocular applications.

PREFORMULATION CHARACTERIZATION OF AQUEOUS EXTRACTS FROM THE LEAVES OF ANTIMALARIAL PLANTS-ARTEMISIA ANNUA L., VERNONIA AMYGDALINA DEL., AND MICROGLOSSA PYRIFOLIA (LAM.) KUNTZE

JIMMY R. ANGUPALE — 2025-01-07

Objective: The current study aimed at characterising relevant physical and chemical properties of antimalarial aqueous extracts from the leaves of Artemisia annua (Aa), Vernonia amygdalina (Va), and Microglossa pyrifolia (Mp) to build a solid foundation for the development of stable dosage forms.

Methods: The aqueous extracts were profiled for key antimalarial chemical markers, aqueous solubility, partition coefficient, permeability, and powder flow properties using standard procedure with modifications where applicable. The powder compaction behaviours were studied using Kawakita and tablet ability models.

Results: Aa extract had 11.2 % of total flavonoids and 0.27 % of artemisinin as its antimalarial chemical markers. Va and Mp extracts contained 0.07 % and 28.5 % total terpenoids as their respective chemical markers. All the extracts exhibited high solubility and low permeability, qualifying them as class III crude drugs based on the biopharmaceutical classification system (BCS). Mp had excellent flow (angle of repose 18.9, Hausner Ratio 1.2, and Carr’s Index 13 %) while Va and Aa had passable flow, thus requiring a glidant. The powder samples underwent plastic deformation, according to the Kawakita plot. Aa also showed the highest level of tabletability, followed by Va, and lastly, Mp (Area under curves of 18.5, 9.2, and 7.8 for Aa, Va and Mp, respectively).

Conclusion: Based on their chemical and physical properties, the Aa, Va, and Mp aqueous extracts can be incorporated into stable, bioavailable, and modern herbal drug delivery systems or dosage forms.

DESIGN AND OPTIMIZATION OF ACYCLOVIR LOADED SOLID LIPID NANOPARTICLES: A SUSTAINED RELEASE APPROACH

Deevan Paul A — 2024-01-07

Objective: This study aims to develop Acyclovir-Loaded Solid Lipid Nanoparticles (ASLN) prepared through homogenisation and evaluate their efficacy.

Methods: ASLN were formulated using Gelucire 43/01, Polyvinylpyrrolidone (PVP), Tween 80, and Stearic acid in varying ratios through solvent evaporation and homogenisation. Lipids and Acyclovir were melted together and then emulsified using a homogeniser. Particle size distribution was assessed by Dynamic Light Scattering (DLS), and Zeta Potential was measured using electrophoretic mobility. The cumulative drug release profile was analyzed to determine sustained release characteristics. Zero-order kinetic modelling was applied to elucidate the release mechanism, indicating diffusion rate-limited drug release. Comparative studies with marketed Acyclovir formulations were conducted to assess efficacy and performance.

Results: All formulations exhibited satisfactory characteristics: Particle size of 185.6±4.28 nm, Zeta potential of-24.15±5.43 mV, Polydispersity Index of 0.192±3.11, and Drug Entrapment Efficiency of 77.06±4.3%. In vitro release studies of ASLN formulation F12 showed prolonged drug release (90.88% cumulative release by the 8th hour), in sustained drug availability. Comparative studies highlighted the efficacy of ASLN compared to commercial acyclovir products. The kinetic analysis confirmed zero-order kinetics and diffusion rate-limited drug release for all formulations.

Conclusion: In conclusion, the formulation of ASLN using Gelucire 43/01, Polyvinylpyrrolidone (PVP), Tween 80, and Stearic acid produced nanoparticles with favourable characteristics. These included appropriate particle size, zeta potential, and high drug entrapment efficiency. In vitro studies demonstrated sustained drug release, suggesting ASLN as promising carriers for enhancing Acyclovir's therapeutic efficacy.

DESIGN AND CHARACTERIZATION OF GLIBENCLAMIDE-CAFFEIC ACID COCRYSTALS VIA CRYSTAL ENGINEERING

JYOTI MALIK — 2025-01-07

Objective: The present work aims to prepare and characterize glibenclamide cocrystals.

Methods: Glibenclamide was chosen as a model drug due to its low solubility and classification as a Biopharmaceutical Classification System (BCS) class II drug. Among the various methods for selecting appropriate coformers, the pKa and thermal methods were employed. Using these approaches, a formulation with caffeic acid, prepared through the solvent evaporation method, demonstrated the best results as evaluated by parameters such as dissolution rate, X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Hot Stage Microscopy (HSM), Scanning Electron Microscopy (SEM).

Results: In the FTIR spectra, the sulfonamide group of the drug formed hydrogen bonds with the hydroxyl groups of the coformer, suggesting the presence of hydrogen bonding interactions between the components. HSM and DSC revealed that the melting point of the cocrystals occurred at a different temperature for the pure drug and coformer. This significant change in the melting point indicates the formation of a new crystalline phase in the cocrystals, suggesting that the drug and coformer interact at the molecular level to form a unique solid structure. XRD analysis showed diffraction peaks at distinct points with higher intensity in the cocrystals, indicating a new crystalline structure. SEM images of the cocrystals revealed a well-defined crystalline morphology, which differed from the irregular shapes of the pure drug and coformer. The cocrystals demonstrated a significantly improved dissolution rate compared to the pure drug and marketed formulation. In animal studies conducted on male Wistar rats, cocrystals reduced blood glucose levels more rapidly than pure glibenclamide. This enhanced antidiabetic efficacy suggests that the cocrystal formulation not only improves dissolution but also accelerates the therapeutic onset of action.

Conclusion: These findings confirmed that the glibenclamide cocrystals prepared with caffeic acid help effectively improve the drug’s low solubility.

FORMULATION, CHARACTERISATION AND OPTIMISATION OF NATURAL ARGAN OIL MICROEMULSION FOR TOPICAL DELIVERY

HIND OUHADDOUCH — 2025-01-07

Objective: The purpose of this study was to develop, optimize and characterize a stable microemulsion of Moroccan cosmetic Argan oil.

Methods: In this work, microemulsion system was studied by the construction of phase diagrams using titration method. At first, various surfactants (Brij56®, Tween 80®, Solutol®, Tween 20® and Labrasol®) and various weight ratio surfactant/cosurfactant (1:0, 3:1, 2:1 and 1:1) were tested to select the optimal surfactant and concentration to use. The microemulsions with tween80 were evaluated with different techniques using various parameters such as droplet size, transmittance, viscosity and pH. Stability studies of these microemulsions were conducted for 8 w at 5 °C, 25 °C and 40 °C, and underwent centrifugation at 3000 rpm and ultracentrifugation at 10,000 rpm.

Results: The largest microemulsion formation area was achieved for the microemulsions containing Tween 80/PEG 400 at a ratio of 3:1. The obtained microemulsions M1 to M12 were homogeneous. More the percentage of PEG 400 increases, more the pH of the preparations and their viscosity decreases, while preparations with a high oil content have low transmittance. Thermodynamic and physical stability shows that only samples with a minimum of 31.5% of Tween 80 and a maximum of 9% of oil showed good stability.

Among the stable preparations, M11 (9% O, 10% W and 40.5/40.5% S/Cos) was the formula which exhibited properties such as transparency, soft acidic pH and low viscosity, making it suitable for cutaneous use.

Conclusion: The use of pseudo-ternary phase diagrams allows for the development of an optimal microemulsion with perfect stability.

QUALITY BY DESIGN-DRIVEN STATISTICAL SCREENING APPROACH TO SELECT EFFECTIVE VARIABLES FOR THE FORMULATION DEVELOPMENT OF PEGYLATED BILOSOMES FOR AN ANTIFUNGAL DRUG

DEVIKA NAYAK — 2025-01-07

Objective: The study aimed to use a quality-by-design approach to screen out the most suitable process and formulation parameters for developing antifungal drug-loaded pegylated bilosomes.

Methods: Thin film hydration technique was used to prepare the formulations. A design experiment [Design Expert^® software; Design of Experiments (DOE)] employing two levels at three factors was used to conduct eight runs to select and screen formulation and process variables. It was assessed for different response variables, such as Particle Size (PS), Polydispersity Index (PDI), Zeta Potential (ZP), and Entrapment Efficiency (%EE). The screened formulation was evaluated for in vitro drug release and kinetic model evaluation.

Results: The significance of each term in the model was evaluated using an Analysis of Variance (ANOVA). Statistical model terms with a significant P-value of less than 0.05 and graphical analysis (Interaction plot, Pareto chart, and 3D plots) generated by DOE version 13 demonstrated that Span 60, Brij C2, and amplitude of 30% were effective variables for formulating pegylated bilosomes with a desirability value of 0.965. The validated formulation showed a PS of 299.1±5.12 nm, PDI of 0.481±0.07, ZP of-36.6±0.55 mV, and %EE of 79.25±2.75. The in vitro release showed a sustained drug release of 55.53±6.75% over 24 h.

Conclusion: Statistical screening approach using a full factorial design can serve as a valuable tool in identifying and screening significant variables for developing antifungal-encapsulated pegylated bilosomes formulations.

ETHOSOMES CARRYING ETODOLAC-EFFECTIVE DRUG CARRIER AS TOPICAL DOSAGE FORM IN THE TREATMENT OF RHEUMATOID ARTHRITIS

ASHWINI A. BACHHAV — 2025-01-07

Objective: The priority-based objective of this research was to develop and evaluate the etodolac loaded Ethosomes as topical delivery in Rheumatoid Arthritis autoimmune disease.

Methods: The ethosomes (EE1-EE6) were prepared with varied concentrations (10%-60% v/v) of ethanol by using Rotary evaporator. The prepared Ethosomes evaluated for %EE (Entraptment Efficiency), Zeta potential, SEM (Scanning Electron Microscopy), TEM (Transmission Electron Microscopy), Vesicle size, In vitro release, In vivo study, Irritancy test, stability test etc.

Results: Prepared ethosomes analysed for zeta potential, vesicle size and % entrapment efficiency and ranges are found to be-18.50mV to-64.53mV, 166.66 nm to 848.97 nm and 53.15% to 89.35%, respectively. Furthermore, when these ethosomes were incorporated in Carbopol 940 gels (EEC1-EEC6), it evaluated for appearance, spredability, pH, viscosity study, drug content and In vitro drug release. All ethosomal gels show satisfactory results. After optimization of ethosomes (EE1-EE6) and ethosomal gels (EEC1-EEC6) on previous criteria, optimised formulations EE4 and EEC4 characterised for SEM, TEM, Ex-vivo permeation, Irritancy, In vivo and different analytical evaluation. The values of r² were found higher for the first-order model and Korsmeyer-Peppas model for all formulations. Irritancy test shows safe use of formulation and in vivo test shows that EEC4 had a significant inhibitory effect on edema, which was developed in the right paw of rat by injecting carrageenan when it compared with plain Carbopol gel and marketed formulation.

Conclusion: The present study has confirmed that the formulated Etodolac Ethosomal gel can be used as best vehicle for topical administration, which may be used for the management of rheumatoid arthritis.

BOX-BEHNKEN OPTIMIZATION OF MELOXICAM MICROCAPSULE SCAFFOLDS FOR PRECISION DRUG DELIVERY IN ARTHRITIS: ENHANCED STABILITY, EFFECTIVE STERILIZATION, AND IN VIVO THERAPEUTIC POTENTIAL

SAMPATH KUMAR — 2025-01-07

Objective: This study aims to develop and evaluate an innovative implantable drug delivery system using gelatin microspheres loaded with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), namely meloxicam (MXM), integrated into a gelatin scaffold. This system is designed to enhance drug delivery efficiency and sustain drug release.

Methods: MXM-loaded microspheres with a 1:1 ratio of Poly Lactic Acid (PLA) and Poly Lacto Glycolic Acid (PLGA) were optimized for size, yield, efficiency, and release. Gelatin scaffolds were designed as rod-shaped implants, tested for stability and degradation in pH 7.4 and pH 4.0 buffers at 37 °C for 100 d, and sterilized with γ-radiation. Implants were evaluated in rabbits, with blood samples analyzed via High-Performance Liquid Chromatography (HPLC) for pharmacokinetic parameters statistically analyzed (P<0.05).

Results: The microspheres with a 1:1 ratio of PLA and PLGA demonstrated favorable characteristics such as smaller particle sizes, high yield, and efficient drug entrapment and release. Optimization using Design Expert resulted in highly desirable scaffolds, evidenced by a desirability factor close to one across all assessed variables. The scaffolds exhibited robust physicochemical properties, including sustained drug release over an extended period, highlighting their potential for diverse biomedical applications. Implants showed greater stability in pH 7.4 buffer solutions in contrast to pH 4.0 over 100 d, with higher mass loss in acidic environments (14.4% vs. 9.66%). γ-Radiation sterilization effectively prevented microbial contamination. In vivo studies confirmed MXM detection in plasma, with Scaffold-MXM microspheres (iS-MMS-17) (optimized implantable scaffold) showing higher mean C_max values and significant Area Under Curve (AUC) parameters, suggesting its potential for effective therapy.

Conclusion: The study found that the scaffolds exhibited strong physicochemical properties and sustained drug release, making them suitable for biomedical use. Implants were more stable at pH 7.4 than at pH 4.0, and γ-radiation effectively prevented microbial contamination. In vivo studies confirmed MXM detection, with iS-MMS-17 showing promising pharmacokinetic parameters for pain and arthritis therapy.

THE EFFECT OF DIFFERENT CONCENTRATION OF β-CYCLODEXTRIN AND GUM ARABIC ON THE MICROENCAPSULATED MORINGA SEED OIL BY USING THE SPRAY DRYING METHOD

NUUR AANISAH — 2025-01-07

Objective: The aim of this study was to determine the impact of various concentrations of β-cyclodextrin and gum arabic on the characteristics of Microencapsulated Moringa Seed Oil (MSO).

Methods: The soxhlation method was used to extract MSO. The resulting MSO was microencapsulated employing a spray dryer. The variations in of β-cyclodextrin: Gum arabic concentrations were made to determine the coating material suitable for this formula. The characterization includes organoleptic tests, FTIR, encapsulation efficiency, morphology, particle size and moisture content of microencapsulated MSO.

Results: The results obtained from the particle size for F1, F2, F3, F4, and F5 were 5.42; 4.29; 4.23; 4.34; 5.15 µm, respectively. Then the percentage of encapsulation efficiency obtained was 74.42±0.13; 78.81±0.12; 82.27±0.07; 93.94±0.09; 71.50±0.11, respectively. The IR spectra shows no chemical interactions that occurred in the formulation of microencapsulated MSO.

Conclusion: In conclusion, microencapsulated MSO formulated with β-cyclodextrin (40% w/v) was recommended as the most optimal formula with a smaller particle size (4.34 µm) among others and exhibited the highest microencapsulation efficiency.

OPTIMIZATION OF SELF NANO-EMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) FORMULA OF COMBINED 70% ETHANOLIC EXTRACT OF BENALU BATU (BEGONIA MEDICINALIS) HERBS AND KELOR (MORINGA OLEIFERA L.) LEAVES USING SIMPLEX LATTICE DESIGN METHOD

MUHAMMAD SULAIMAN ZUBAIR — 2025-01-07

Objective: This research aims to perform Self Nano-Emulsifying Drug Delivery System (SNEDDS) formulation of combined ethanolic extract of benalu batu (Begonia medicinalis) herbs and kelor (Moringa oleifera) leaves, determine the optimal concentration based on physicochemical characteristics as well as the phytochemical contents and in vitro anticancer activity.

Methods: Surfactant and co-surfactant concentrations were determined by Design Expert v.13 software with Simplex Lattice Design (SLD) method. The phytochemical contents were measured by using a UV-Vis spectrophotometer, and the inhibition activity on HeLa cancer cells was tested by using the MTT method.

Results: Design Expert with the SLD method produces five design formulas. The most optimal SNEDDS formula based on the SLD method was formula 5, which contains a combination of extract of benalu batu herbs and kelor leaves with a concentration ratio of 1:1 (100 mg: 100 mg), 12% Virgin Coconut Oil (VCO), 64% tween 80, and 16% propylene glycol. The optimal formula has the characteristics of an emulsification time of 39.30±3.055 seconds, a transmittance percentage of 92.25%±0.004, a particle size of 14.43 nm±0.306 with a Polydispersity Index (PI) of 0.237, pH of 4.70±0.031 and viscosity of 355 cps±2.6. It also contains a total phenolic content of 5.517±0.382 mg/g GAE, total flavonoids of 8.501±0.695 mg/g QE, and total saponins of 17.991±0.052 mg/g EE. In addition, it also possesses a high percentage of cell death of Hela cancer, which is 84.334% at a concentration of 200 µg/ml.

Conclusion: Formula 5 has the potential for anticancer activity with good characteristics as SNEDDS formula.

FORMULATION AND CHARACTERIZATION OF ISRADIPINE SOLID DISPERSION WITH ENHANCED SOLUBILITY

ZAID HADI FAKHRULDEEN — 2025-01-07

Objective: This study aimed to prepare and optimize solid dispersion of isradipine, an antihypertensive drug with poor aqueous solubility using two different methods, namely, solvent evaporation and fusion.

Methods: Twenty-two formulas of isradipine solid dispersion were prepared using one of the following carriers: Poloxamer 407 (PXM 407), Polyethylene Glycol 4000 (PEG 4000), Polyethylene Glycol 6000 (PEG 6000) and urea at different carrier-to-drug ratios. The produced solid dispersion formulations were evaluated for their percentage yield, drug content, solubility, and in vitro dissolution. Further investigations were performed for the selected formula; these include Differential Scanning Calorimetry (DSC), and Powder X-Ray Diffraction (PXRD) studies to evaluate the crystalline state of the drug. Besides Fourier Transformation Infrared (FTIR) spectroscopy was conducted to evaluate drug-carrier compatibility.

Results: The results of this study showed that all the prepared formulas resulted in improvement in saturation solubility. Run 14 (which consists of PXM 407: isradipine in a 5:1 ratio) demonstrated a substantial increase in solubility, resulting in approximately 16 times higher solubility than the pure drug. The results of DSC and PXRD studies demonstrated complete dispersion of the drug in the carrier or amorphization of the drug. Furthermore, FTIR results indicated drug-carrier compatibility.

Conclusion: From this study, it was evident that solid dispersion of isradipine in the previously mentioned carriers is an effective and efficient method to enhance its solubility. The best solubility enhancement and release profile was observed in run 14 (which combines PXM 407: isradipine in a 5:1 ratio), which was selected as the optimum formula.

BEYOND-USE DATE DETERMINATION OF CETIRIZINE HYDROCHLORIDE SYRUP PREPARATION

CATUR JATMIKA — 2025-01-07

Objective: To determine Beyond Use Date (BUD) of cetirizine hydrochloride syrup preparation by analyzing cetirizine concentrations using High-Performance Liquid Chromatography (HPLC) with an Ultraviolet (UV) detector.

Methods: The analysis was carried out using mobile phase acetonitrile-phosphate buffer pH 3 (50:50 v/v), flow rate 1 ml/min with isocratic elution, and detected using a UV detector at 232 nm. The BUD was determined by measuring the cetirizine level in the syrup sample since the primary packaging was opened (day 0) for 5 w of storage.

Results: The analytical method was selective and specific. The linearity results show a correlation coefficient (r) of 0.9998 in the 4-32 g/ml concentration range. The limit of detection (LOD) and limit of quantification (LOQ) values were 0.5 µg/ml and 1.7 µg/ml, respectively. The method satisfies accuracy, precision, robustness, and ruggedness criteria. The data showed a decrease in cetirizine concentration level in preparation within 5 w.

Conclusion: This study successfully determined the BUD of cetirizine hydrochloride syrup by analyzing cetirizine concentrations using HPLC with a UV detector. The results revealed a progressive decrease in cetirizine concentration over five weeks of storage, and the BUD was established at 25 d. This finding is significant, providing valuable guidance for pharmacists and healthcare providers in managing the use of the medicine after the primary packaging is opened.

A STUDY OF PHARMACOKINETIC INTERACTION BETWEEN MANGIFERIN AND ATORVASTATIN IN HYPERLIPIDEMIC RATS

MEESA MADHAVI — 2025-01-07

Objective: The main aim of this study is to determine the effect of Mangiferin on the pharmacokinetics of Atorvastatin in hyperlipidemic rats.

Methods: The plasma concentration of Atorvastatin (ATR) to the time profile was calculated using High Performance Liquid Chromatography (HPLC). The experiment was carried out in normal and High Fat Diet (HFD) induced hyperlipidemic rats in single and multiple-dose treated rats for pharmacokinetic study. HFD was administered to the rats for 8 w to induce hyperlipidemia. Each group contains six animals, Group I received ATR alone (20 mg/kg), Group II received Mangiferin (MGF) (40 mg/kg) followed by ATR for Single-Dose Interaction(SDI), Group III received MGF for 7 days, followed by ATR on 8^th d for Multiple Dose Interaction (MDI). Blood samples were collected and estimated for pharmacokinetic parameters such as the Area under Curve (AUC), Maximum Plasma Concentration (C_max), Time to achieve Cmax (Tmax), Biological Half-Life (t_1/2), mean Residence Time (MRT) and Volume of distribution (V_d), Clearance (CL) and Elimination Rate Constant (K_e).

Results: In normal and disease-induced rats of SDI and MDI studies it has shown increased plasma concentration of ATR in the presence of MGF. MGF significantly increased the following pharmacokinetic parameters: C_max (83.56±5.94 ng/ml) in SDI, (100.28±6.37 ng/ml) in MDI, AUC (265.25±14.73ng. h/ml) in SDI, (299.04±14.11ng. h/ml) in MDI. t_1/2, V_d, and MRT were also enhanced in both studies. However, CL and K_e were reduced significantly.

Conclusion: This study revealed that MGF altered the ATR pharmacokinetics. This could be due to MGF Cytochrome P450 (CYP3A) enzyme inhibition.

FORMULATION AND IN VITRO EVALUATION OF VENLAFAXINE MATRIX TABLETS USING GUM KONDAGOGU AS EXCIPIENT

ANIL KUMAR DINDIGALA — 2025-01-07

Objective: A naturally obtained Gum Kondagogu (GK) investigated as a novel matrix-forming material for sustained drug delivery using Venlafaxine HCl (VH) as a model drug.

Methods: The VH tablets were prepared with different concentrations of GK along with other excipients such as sodium alginate and zinc acetate. The compressed tablets were then evaluated for pre-compression parameters, including flow properties and post-compression parameters, such as hardness, friability, and drug content uniformity. Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) studies were conducted to assess potential interactions between the excipients and the drug. Additionally, the lead formulation underwent accelerated stability studies at 40±2 °C/75±5% RH for 3 mo to evaluate the stability and consistency of drug release.

Results: The compressed tablets of VH with GK were found to have acceptable pre-and post-compression parameters. Among the various formulations tested, the one containing 0.25%w/v of GK, 0.3% of sodium alginate, and 0.3% of zinc acetate demonstrated a release profile closely matching that of a commercial tablet dosage form. FTIR and DSC studies confirmed that there were no interactions between the excipients and the drug. The lead formulation maintained stability over 3 mo of accelerated stability studies, with no significant changes in drug release observed during this period.

Conclusion: GK has shown potential as a controlled release agent for oral dosage forms, particularly for drugs like VH. The formulation containing 0.25%w/v of GK, 0.3% of sodium alginate, and 0.3% of zinc acetate exhibited a release profile similar to that of a commercial product and maintained stability under accelerated conditions. These findings suggest that GK could be a viable option for developing control-release oral formulations.

FORMULATION AND PHARMACOKINETIC STUDY FOR LIQUISOLID COMPACTS OF CINACALCET HCL

M. SOMESU — 2025-01-07

Objective: The objective of this study is to enhance the flowability, compressibility, and oral bioavailability of Cinacalcet Hydrochloride (HCl) using the liquisolid technique. It is a calcimimetic drug approved for treating secondary hyperparathyroidism in chronic kidney disease patients faces challenges due to its poor aqueous solubility and low bioavailability (20-25 %).

Methods: To address this, we formulated cinacalcet HCl liquisolid compacts with tween 80 and labrasol as the non-volatile solvents, neusilin US2 as the carrier material, and aerosil as the coating material. Our comprehensive analysis included Fourier-transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray diffraction (P-XRD), kawakita analysis and heckel analysis, quality control tests and pharmacokinetic study.

Results: The liquisolid powders of cinacalcet HCl exhibited desirable flowability and compressibility for processing into a tablet dosage form. Kawakita and Heckel analysis revealed reduced cohesiveness and increased plasticity. FT-IR and DSC studies did not exhibit any interaction between drug and carriers. P-XRD study for liquisolid formulation did not exhibit any peaks due to the presence of cinacalcet HCl in molecular form. In vitro dissolution study revealed 37 times improvement in dissolution at 30 min. The Area Under the Curve (AUC) values showed a 2.5-fold increase in oral bioavailability.

Conclusion: Overall, the liquisolid approach promises to develop a stable and scalable solid dosage form with improved flowability, compressibility, and oral bioavailability.

3D PRINTING IN THE PHARMACEUTICAL INDUSTRY: A SPECIAL CONSIDERATION ON MEDICAL DEVICE AND ITS APPLICATIONS

VIVEKANANDAN ELANGO — 2025-01-07

3 Dimensional (3D) printing has seemed to be the technology of radical development for the pharmaceutical industry, particularly in medical device manufacturing. The current review elaborates on the applications of 3D printing, challenges, and potentials in pharmaceutical medical devices. The technology allows for complicated personalized devices with accuracy and cost-effectiveness as never before, bringing in the key applications for this technology in the fields of prostheses, orthoses, surgical guides, audiology devices, and bioresorbable implants. It brings along customization, better pre-operative planning, and new drug delivery systems, but there are quality control and regulatory challenges to be faced: material selection, process validation, sterilization, and scalability. In view of this upcoming technology, the regulatory bodies are having to update their guidelines to ensure continued safety and efficacy. On the road ahead, with artificial intelligence, nanotechnology, and 4 Dimensional (4D) printing, future developments could make sophisticated medical equipment and change the management and outcome of diseases. While 3D printing opens up newer routes of innovation in the pharmaceutical industry, there are major concerns on issues of scalability and regulatory matters. This technology will thus make a significant impact on healthcare delivery through these coming decades, with changes in the global research and regulatory landscapes.

UNDERSTANDING NANO-BIO-INTERACTIONS WITH CORRESPONDING BIOLOGICAL RESPONSES: INSIGHTS AND IMPACT ON NANO ASSEMBLY AND DISASSEMBLY

POONAM JOSHI — 2025-01-07

Using stimuli-responsive Bio Interactions with controlled nano-assembly is proving a potent method for generating theranostic nanosystems that satisfy the needs of modern medicine for example, targeted delivery which is very helpful for cancer treatment with minimum side effects. However, because of the limitations in our knowledge, this promising topic is still in the proof-of-concept stage. This study provides an overview of the most recent theoretical and experimental advancements in biological fate, functional activity of nano-assemblies, and nano-bio interactions with exogenous stimulus-triggered systems (Light-responsive systems, Ultrasound-responsive systems, Magnetic field-responsive systems, and Thermal-responsive systems)endogenous stimulus-triggered systems (Ph-Responsive Systems, Redox-responsive systems, Enzyme-responsive systems) and multi stimuli system. Related biological consequences reactions. Firstly, we intend to thoroughly explain these relationships in this review. The relationship between interaction studies and nano-based stimuli; the important physicochemical characteristics of in vivo stimuli, such as responsive assembly and disassembly; biological applications; and pharmacokinetic (pk) parameters based on nano-bio interaction.

EXPLORING POTENTIAL OF NOVEL HETEROCYCLIC COMPOUNDS AND THEIR STRUCTURE-ACTIVITY RELATIONSHIP IN PROSTATE CANCER TREATMENT

KAVANA KRISHNA NAYAK — 2025-01-07

Prostate cancer is one of the leading causes of male death globally, and its overall incidence flaunts a rising trend over the years. Currently available treatment modalities for prostate cancer suffer from severe toxicity, unpredictable efficacy, high costs, and the emergence of resistance towards anti-cancer compounds. This substantiates the need to develop novel and potent anti-proliferative agents against prostate cancer. Multiple cellular mechanisms underlie the development of prostate cancer and, thus, multiple drug gable targets. In recent years, researchers have been conducting a myriad of investigations in this direction. This work recapitulates the synthesis of 78 such molecules based on recent references. These compounds are classified and tabulated according to the moiety that they possess. Further, the review study highlights the potent member of each chemical class. In addition, the review provides fundamental insights into the design and development of such compounds through the structure-activity relationship of each series of compounds, thereby unlocking new doors for future exploration.

A REVIEW ON RECENT ADVANCES IN HYDROGELS AS DRUG DELIVERY SYSTEM

AYA M. GHANEM — 2025-01-07

Hydrogels are hydrophilic three-dimensional polymeric networks which has the capability to absorb water or biological fluids. These polymeric network is formulated through chemical crosslinking or physical crosslinking mechanisms. Several polymers of synthetic and natural origin can be used to form hydrogels. Mechanical properties, swelling and biological properties are about the most significant hydrogels properties that can affect their morphology and structure. Hydrogels are promising biomaterials due to their significant properties as hydrophilicity, biodegradability, biocompatibility and non-toxicity. These characteristics make hydrogels appropriate for medical and pharmaceutical application. This review discusses the types of hydrogels, their properties, mechanism of preparation and applications of hydrogels as drug delivery system.

AN EMERGING ERA IN DRUG DELIVERY SYSTEM FOR TREATMENT OF MALARIA: WAVE FROM CONVENTIONAL TO ADVANCED TECHNOLOGY

TAMNNA SHARMA — 2025-01-07

Colonization of the erythrocytic stages of Plasmodium falciparum has become a challenging aspect in every drug delivery system because it is responsible for each clinical manifestation and life-threatening complication in malaria. With the emergence of resistance in malarial parasites in the recent past, developing a vaccine against malaria is still a long-drawn-out affair. However, recent reports of the recombinant protein-based vaccine against malaria vaccine from Glaxo Smith Kline have initiated a new ray of hope. In such a scenario, the onus of developing a reliable drug against the disease remains the mainstay in fighting against malaria. This review delves into the various attempts carried out by researchers in the past to develop a drug against the erythrocytic stages of the malaria parasite and throws light on a very recent outcome that provides targeted delivery of the drug to the infected erythrocyte using a nanotechnology-based approach. Considering the eventful journey in the beginning, it was the discovery of chloroquine that created an epoch in the treatment of malaria. Due to its low cost and high efficacy, it became the most widely used antimalarial. Until the 1960s, Chloroquine (CQ) was the best solution against malaria but the scenario changed in the 1970s due to widespread clinical resistance in Plasmodium falciparum, and Plasmodium vivax in various parts of the world. This, in turn, led to the development of novel drug delivery systems using liposomes and Solid Lipid Nanoparticles (SLN) for more effective and site-specific delivery of chloroquine to the infected erythrocytes. Such attempts led to a later use of the nanotechnology-based approach which included the use of nanospheres and nanoparticulate drug carriers.