International Journal of Applied Pharmaceutics <div align="justify"> <p align="justify">International Journal of Applied Pharmaceutics (Int J App Pharm) is a peer-reviewed, bimonthly (onward March 2017) open access journal devoted to the excellence and research in the pure pharmaceutics. This Journal publishes original research work that contributes significantly to further the scientific knowledge in conventional dosage forms, formulation development and characterization, controlled and novel drug delivery, biopharmaceutics, pharmacokinetics, molecular drug design, polymer-based drug delivery, nanotechnology, nanocarrier based drug delivery, novel routes and modes of delivery; responsive delivery systems, prodrug design, development and characterization of the targeted drug delivery systems, ligand carrier interactions etc. However, the other areas which are related to the pharmaceutics are also entertained includes physical pharmacy and API (active pharmaceutical ingredients) analysis. The Journal publishes original research work either as a Original Article or as a Short Communication. Review Articles on a current topic in the said fields are also considered for publication in the Journal.</p> </div> Innovare Academic Sciences Pvt Ltd en-US International Journal of Applied Pharmaceutics 0975-7058 DEVELOPMENT AND VALIDATION OF UV SPECTROSCOPIC METHOD OF PALIPERIDONE PALMITATE IN BULK AND ITS APPLICATION FOR DRUG LOADING AND ENTRAPMENT EFFICIENCY ANALYSIS OF LONG-ACTING INJECTABLE MICROSPHERES <p><strong>Objective: </strong>The objective of the current study was to develop simple, precise and cost-effective ultraviolet (UV) spectroscopic method for estimation of paliperidone palmitate (PP) as a bulk and in the polymeric depot dosage form.</p> <p><strong>Methods: </strong>UV spectrophotometer with quartz sample cells and spectral manager software was used for analysis samples. 20 % Methanol in Mili-Q-Water was used as a solvent for the sample and standard preparations. Method validation was carried out as per ICH Q2 (R1) guidelines. Stress degradation studies were carried out to check the stability-indicating performance of the developed method. The validated method was applied for the estimation of the PP content of long-acting injectable microspheres of PP.</p> <p><strong>Results: </strong>The wavelength of maximum absorption was found to be 283 nm. The proposed method was validated in the range of 5-30 µg/ml of PP. The mean recovery for 80%, 100% and 120% standard solution was found to be 99.03%, 99.21% and 99.35% respectively with less than 2% relative standard deviation (RSD). Intra-day and inter-day method precision ranged from 0.54 to 1.62% and 0.67 and 1.24% respectively. Limit of detection (LOD) and limit of quantitation (LOQ) were estimated to be 0.03 and 0.10 µg/ml respectively. The developed method was found to be robust and rugged. Stress degradation studies were carried out under acidic, alkaline, hydrolytic and oxidative and photo stress. The proposed method was capable to detect changes in assay due to stress conditions.</p> <p><strong>Conclusion: </strong>The developed method was successfully employed for routine analysis of drug loading in long-acting injectable microspheres of PP.</p> SANDIP MALI NISHANT OZA Copyright (c) 2021 Sandip Mali 2021-07-07 2021-07-07 87 93 10.22159/ijap.2021v13i4.41583 DESIGN, DEVELOPMENT AND IN VITRO EVALUATION OF ERLOTINIB LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES BY BOX BEHNKEN DESIGN <p><strong>Objective: </strong>To formulate and evaluate Erlotinib loaded Liquorice crude protein (LCP) nanoparticles from the powdered liquorice root (<em>Glycyrrhiza glabra</em>) using Box-Behnken design.</p> <p><strong>Methods</strong><strong>:</strong> Erlotinib loaded liquorice crude protein nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) and gluteraldehyde (8% v/v) as cross linking agent. Box-Behnken design with 3 factors, 3 levels and 3 responses was used to optimize the prepared nanoparticles. The independent variables were taken as A) Erlotinib concentration B) LCP concentration and C) Incubation time with responses R1) Drug entrapment efficiency R2) Drug Release and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, and <em>in vitro </em>drug release studies in PBS pH 7.4 (26 h) were carried out. The experimental values were found to be in close resemblance with the predicted value obtained from the optimization process. The <em>in vitro</em> cytotoxicity studies of the prepared nanoparticles in lung cancer cell line (A 549) were studied with different concentrations for 24h.</p> <p><strong>Results</strong><strong>:</strong> The average particle size, zeta potential, Polydispersity index (PDI) were found to be 292.1 nm,-25.8 mV and 0.384 respectively. TEM image showed that the nanoparticles dispersed well with a uniform shape and showed not much change during storage. The <em>in vitro</em> drug release showed 41.23% for 26 h in PBS (7.4) and release kinetics showed highest R<sup>2</sup>value (0.982) for Korsmeyer-Peppas model, followed by 0.977 for Higuchi model. The <em>in vitro</em> cytotoxicity of prepared nanoparticles in A 549 cell line showed good results with different concentrations for 24h.</p> <p><strong>Conclusion: </strong>Erlotinib (Erlo) is a BCS class II drug with poor solubility, poor bioavailability and selective tyrosine kinase inhibitor for non small-cell lung cancer (NSCLC) through oral administration. To improve the oral bioavailability and absorption of molecules, plant protein as carriers is used for developing drug delivery systems due to their proven safety. The optimization variables were Conc of Erlo, Conc. of LCP and Incubation time to get responses as drug entrapment efficiency, drug release and particle size. The compatibility between drug and LCP were evaluated by FTIR. </p> GEETHA V. S. MALARKODI VELRAJ Copyright (c) 2021 GEETHA V S, Dr. Malarkodi Velraj 2021-07-07 2021-07-07 94 101 10.22159/ijap.2021v13i4.41580 FEATURES OF THE DEVELOPMENT OF A LYOPHILIZED INJECTABLE DOSAGE FORM OF THE ORIGINAL ANTICANCER DRUG LCS-1208 <p>Objective: Development of a lyophilized injectable dosage form LCS-1208, an original antitumor drug based on an indolocarbazole derivative.</p> <p><strong>Methods: </strong>The prepared solution of the injectable dosage form LCS-1208 is transferred to sterilizing filtration, which is carried out under vacuum on a «Stericup» filter unit with a filter pore size of 0.22 μm. The sterile solution of the injectable dosage form LCS-1208 is poured into sterile vials using a dispenser and lyophilized in a freeze-drying chamber. At the end of drying, the preparation is corked in the chamber of a sublimation unit using a hydraulic device and transferred to crimping with aluminum caps using a seaming machine. Quantitative determination of the drug content was determined by spectrophotometry using a standard sample at λ = 320±2 nm. The pH was determined by potentiometry.</p> <p><strong>Results: </strong>A freeze-drying regimen for the injectable dosage form LCS-1208 has been developed. The required solution freezing temperature was established taking into account the presence of 2 eutectic zones: a solution of LCS-1208 in DMSO (-35 ÷-32) °С, an aqueous solution of Kollidon 17PF (-10 ÷-8) °С. As a result of a series of experiments, the optimal lyophilization regime was chosen that does not require preliminary freezing in a low-temperature chamber, with freezing on the shelves of freeze-drying at a temperature of-47 °C without their preliminary cooling. The most acceptable vial filling volume was determined, amounting to 3 ml, and the rate of temperature rise during secondary drying of the preparation was justified. When using the developed regime of lyophilization of the LCS-1208 solution, it was shown that it can be sublimated while preserving the initial qualitative and quantitative characteristics.</p> <p><strong>Conclusion: </strong>In this article, using the example of creating a lyophilized injectable dosage form LCS-1208 (the original antitumor drug from the indolocarbazole group), the main problems that arose during the lyophilization of the selected composition of the model solution, as well as ways to improve the process.</p> ILYA GULYAKIN ANNA LANTSOVA LYUDMILA NIKOLAEVA MARIA DMITRIEVA NATALIYA OBOROTOVA OLGA ORLOVA NATALIA ZHURAVLEVA Copyright (c) 2021 Ilya Gulyakin, Anna Lantsova, Lyudmila Nikolaeva, Maria Dmitrieva, Nataliya Oborotova, Olga Orlova, Natalia Zhuravleva 2021-07-07 2021-07-07 102 105 10.22159/ijap.2021v13i4.41371 THE EFFECT OF BANGGAI YAM (DIOSCOREA ALATA L.) MODIFICATION ON FILM CHARACTERISTICS AS A FILM COATING MATERIAL FOR MODIFIED RELEASE DOSAGE FORMS <p><strong>Objective: </strong>This study aims to determine the effect of modification of Banggai yam (<em>Dioscorea alata</em> L.) as a coating agent in modified release drug based on the film characteristics.</p> <p><strong>Methods: </strong>Banggai yam starch was physically modified to produce pregelatinized Banggai yam starch (PGBYS) powder as well as chemically to produce pregelatinized Banggai yam starch phthalate (PGBYSP). Powder obtained was each physically and chemically characterized including organoleptics, morphology, tapped density, water content content and degree of substitution. Furthermore, the formulation was made to produce film-coated drug with the same coating agent concentration in 2 formulas: F1 (PGBYSP 6 %) and F2 (PGBYS 6 %).</p> <p><strong>Results: </strong>The results were then evaluated including organoleptics, film thickness, morphology, mechanical strength, and film solubility. Results of evaluation showed that film thickness values for both formulas, ​​F1 and F2 respectively, were 0.13±0.020 mm and 0.18±0.005 mm. Mechanical strength included tensile strength consecutively at values of F1= 0.08±0.005 MPa and F2= 0.27±0.05 MPa; % elongation of F1= 114.16±11.8 % and F2= 164.06±57.94%; Young's modulus of F1= 7.3×10<sup>4</sup>±9.8×10<sup>-5</sup> MPa and F2= 1.8×10<sup>3</sup>±7.9×10<sup>-4</sup> MPa. The solubility of the film-coating in HCl pH 1.2 medium for F1 was 7.9±1.92% and F2 was 25.8±2.42%. In pH 6.8 medium, F1 was 8.6±2.27% and F2 was 11.6±1.44%, while in pH 7.4 medium, F1 was 19.1±5.46% and F2 was 13.1±1.78%. Both film-coated formulas were soluble in alkaline medium, but F2 could not maintain its conditions in acid medium. This proves that the chemical modification product by esterification to form a film can withstand acidic medium.</p> <p><strong>Conclusion: </strong>Therefore, PGBYSP has potential to be used as a coating agent in controlled release drug.</p> YUSRIADI EVI SULASTRI ATHIYAH NUUR AANISAH Copyright (c) 2021 Yusriadi, EVI SULASTRI, Athiyah, Nuur Aanisah 2021-07-07 2021-07-07 106 110 10.22159/ijap.2021v13i4.41343 HPLC ANALYSIS OF AMINO ACIDS CONTENT IN CRAMBE CORDIFOLIA AND CRAMBE KOKTEBELICA LEAVES <p><strong>Objective: </strong>The aim of our study was to establish the content of some primary metabolites, such as amino acids in <em>Crambe cordifolia</em> and <em>Crambe koktebelica</em>. The lack of experimental data induced us to determine these compounds.</p> <p><strong>Methods: </strong><em>Crambe cordifolia</em> and <em>Crambe koktebelica</em> leaves were selected as the objects of the study. The amino acids in the raw materials were determined by the HPLC method.</p> <p><strong>Results: </strong>The results of the research revealed that the leaves of <em>Crambe cordifolia </em>and <em>Crambe koktebelica</em> contain fifteen and sixteen free amino acids respectively. Among the free amino acids L-histidine was presented in <em>Crambe cordifolia</em> leaves in the greatest amount, its content was 12.19 µg/mg. The content of free L-arginine, L-valine, L-phenylalanine, L-isoleucine was the greatest in <em>Crambe koktebelica</em> leaves, it was 2.23 µg/mg, 2.04 µg/mg, 1.74 µg/mg, 1.50&nbsp;µg/mg respectively. The content of bound L-glutamic acid, Glycine, L-arginine, L-leucine was the highest in <em>Crambe cordifolia</em> and&nbsp;<em>Crambe koktebelica</em> leaves.</p> <p><strong>Conclusion: </strong>The results of the study showed that <em>Crambe cordifolia</em> and <em>Crambe koktebelica</em> can be considered as a source of highly digestible amino acids that can be used to treat some diseases.</p> LIUDMYLA SLOBODIANIUK LILIIA BUDNIAK SVITLANA MARCHYSHYN OLHA SKRYNCHUK VICTORIIA KUDRIA Copyright (c) 2021 Liliia Budniak, Liudmyla Slobodianiuk 2021-07-07 2021-07-07 111 116 10.22159/ijap.2021v13i4.41265 EFFECT OF POLYMERIC BLEND ON EX-VIVO PERMEATION STUDIES OF ACECLOFENAC LOADED FILM FORMING GEL <p><strong>Objective: </strong>To date, film-forming systems have been intensively investigated for transdermal drug delivery. Film-forming systems offers various advantages compared over conventional transdermal drug delivery systems. The objective of the present study was to study the effect of polymeric blend on <em>ex-vivo</em> permeation studies of topical film-forming gel of aceclofenac.</p> <p><strong>Methods: </strong>Film-forming gels were prepared by using Hydroxypropyl methylcellulose and Eudragit polymeric blend in varied concentrations, polyethylene glycol 400 as plasticizer, ethanol as solvent and tween 80 as a penetration enhancer. The prepared film-forming gels were evaluated and the influence of the concentration and ratio of polymeric blends used plasticizer and ethanol were investigated.</p> <p><strong>Results: </strong>All the prepared film-forming gels showed satisfactory properties regarding homogeneity, compatibility, viscosity and pH value. Variation in the concentration of polymers showed a variable effect on drug permeation rate from film-forming gels. Almost, all formulations permeated up to 80% of drug in 12 h and formulation F1 showed a maximum release about 97.54 % in 12 h.</p> <p><strong>Conclusion: </strong>Film-forming gels of aceclofenac with sustained-release profile were successfully developed and may provide a promising effective formulation which may improve patient compliance.</p> HIMANI BAJAJ VINOD SINGH RANJIT SINGH TIRATH KUMAR Copyright (c) 2021 Himani Bajaj, Vinod Singh, Ranjit Singh, Tirath Kumar 2021-07-07 2021-07-07 117 122 10.22159/ijap.2021v13i4.41257 TARGETING NUCLEAR FACTOR KAPPA B WITH CHELATED ZINC COMPOUNDS TOWARDS ANTICANCER DRUG DESIGN <p><strong>Objective: </strong>The objective of the study was to analyse the target-ligand interactions between nuclear factor-κB (NF-κB) and chelated Zinc compounds and to explore the anticancer drug potential of these ligands by a bio computational approach.</p> <p><strong>Methods: </strong>Bioinformatics databases and tools were applied for the study. Three dimensional structure of the target NF-κB was retrieved from Protein Data Bank (PDB). The optimized structures of two chelated Zinc compounds, Zinc acetate and Zinc orotate were taken for docking studies with the target using docking tool AutoDock 4.2. Drug properties of the ligands were further assessed by Molinspiration server.</p> <p><strong>Results: </strong>Docking results as predicted by AutoDock and as visualized by PyMol viewer were effective for both the ligands. Comparatively, Zinc orotate showed minimum energy and more interactions with the target. Both the ligands satisfied the Lipinski’s rule of five with zero violations.</p> <p><strong>Conclusion: </strong>The findings emphasized the promising role of chelated Zinc compounds as potent drug candidates in anti-cancer drug design against NF-κB.</p> NAGALAKSHMI K. SHILA S. INBATHAMIZH L. THENMOZHI A. RASAPPAN P. SRINIVASAN P. T. Copyright (c) 2021 Inbathamizh.L 2021-07-07 2021-07-07 123 127 10.22159/ijap.2021v13i4.41650 PHYSICAL AND CHEMICAL STABILITY TEST OF NEEM OIL CREAM (AZADIRACHTA INDICA) USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY <p><strong>Objective: </strong>This study aims to examine the physical and chemical stability of neem oil cream.</p> <p><strong>Methods: </strong>Physical stability was conducted by storing the cream at room temperature (25±2 °C/65 %RH±5 %RH) and high temperature (40±2 °C/75 % RH±5 % RH) for 3 mo. HPLC method using Dionex with UV detection at 219 nm, Shodex (C-18) HPLC packed column (4.6 mmID x 250 mmL), acetonitrile: water [30:70] as mobile phase, 10 min isocratic elution with a flow rate of 1.0 ml/min with volume injection 20 μL was validated then was carried out to measure azadirachtin levels in neem oil cream. The chemical stability of azadirachtin in the cream was determined for 90 days by using this validated method.</p> <p><strong>Results: </strong>The neem oil cream was physically stable. The HPLC method of azadirachtin meets all the validation parameters and can be used to analyze the chemical stability of azadirachtin in neem oil cream. Neem oil cream was stable for 4 w at 25 °C and for 1 w at 40 °C.</p> <p><strong>Conclusion: </strong>The neem oil cream was either physically or chemically stable for 4 weeks at 25 <sup>o</sup>C and 1 week at 40 <sup>o</sup>C</p> FEBRINA AMELIA SAPUTRI PATIHUL HUSNI NORISCA ALIZA PUTRIANA Copyright (c) 2021 Febrina Amelia Saputri 2021-07-07 2021-07-07 128 134 10.22159/ijap.2021v13i4.41539 POROUS PLASTIC MATRIX TABLETS OF LEVETIRACETAM FOR ZERO-ORDER CONTROLLED RELEASE: DEVELOPMENT AND FORMULATION OPTIMIZATION <p><strong>Objective: </strong>The prior objective of the current research work was to develop once-daily levetiracetam extended/controlled-release tablets having zero-order release kinetics with the plastic matrix as the release retarding element. For a high water-soluble drug, the formulation of a dosage form so as to have an extended drug release has always been a difficult task.</p> <p><strong>Methods: </strong>In the current work, levetiracetam which is a highly soluble drug was taken as the model drug for which extended-release matrix tablets were developed using varied plastic polymers like Polyvinyl acetate (PVAc), Polyvinyl chloride (PVC), Eudragit RSPO and Eudragit RLPO. PVP was considered as a pore-forming agent and PEG 6000 was taken as a water regulating agent. The porous plastic matrix tablets were prepared by embedding the drug in solvent-activated polymer dispersion followed by drying, sieving, mixing with other excipients and finally compressed. Including physical characterization studies and drug release studies, the tablets were subjected to SEM studies before and after the dissolution studies to analyze the effect of the pore former.</p> <p><strong>Results: </strong>Pre-compression mixtures exhibited good packageability of 81-92% and hence the compressed tablets were strong enough with good tensile strength in the range of 0.78–0.90 N/mm<sup>2</sup>. Drug release study results showed that the drug release was controlled for a period of 12–24h. PVAc had shown better controlled-release among all the plastic polymers taken. PEG 6000 in combination with PVP produced the desired zero-order drug release.</p> <p><strong>Conclusion: </strong>The levetiracetam porous plastic matrix tablets were developed with zero-order drug release that was effectively controlled for 24hr.</p> RAVI PARIMI RAMA RAO VADAPALLI K. E. PRAVALLIKA Copyright (c) 2021 Parimi Ravi 2021-07-07 2021-07-07 135 141 10.22159/ijap.2021v13i4.41172 DEVELOPMENT AND IN VITRO ASSESSMENT OF BUSPIRONE LOADED IN SITU NANOEMULSION GEL <p><strong>Objective: </strong>Buspirone, is a medication primarily used for generalized anxiety disorder (GAD), relieve symptoms of anxiety and unipolar depression. This drug exhibit low bioavailability (approximately 5%) due to extensive first-pass metabolism and non-targeted delivery results in numerous side effects. It is taken by mouth, and it may take up to four weeks to have an effect. The present investigation aimed at the development of buspirone in situ nanoemulsion gel to evaluate its potential for efficacious nose to brain drug delivery.</p> <p><strong>Methods: </strong>Buspirone-loaded nanoemulsions (BNEs) were prepared by aqueous titration (Spontaneous emulsification) method using Oleic acid, Tween 80, and PEG 400 as oil, surfactant and cosurfactant respectively. The NEs (FC1-FC8) were characterized for pharmaceutical characteristics (Appearance, thermodynamic stability, polydispersity index (PDI) value, globule size, pH, Viscosity, Conductivity and Refractive index). <em>In vitro</em> drug release study from nanoemulsions (NEs) was carried out using Keshary–Chien cell (KC cell, 25 ml) in phosphate buffer pH 5.5.</p> <p><strong>Results: </strong>Formulation FC5 with mean globule size of 105.4±1.10 nm, PDI value 0.230±0.01 and drug release 90±0.39% in 6 h (h) was developed as mucoadhesive nanoemulsion gel formulation with 17.5 % W/W of Pluronic F127. The nanoemulsion gel was homogenous, transparent, and possessed a bioadhesive strength of 1605 Dyne/cm2. <em>In vitro</em> cumulative drug release was found to be 90.00±0.39 % at the end of 6 h.</p> <p><strong>Conclusion: </strong>The gel had no effect on the structural integrity of nasal mucosa. Hence, the study postulates that In situ nanoemulsion gel of buspirone could be used as an intranasal formulation for targeted brain delivery via nasal route.</p> KAMALESH TRIPATHI NIRANJAN KUMAR MANNA Copyright (c) 2021 kamalesh tripathi, Niranjan k manna 2021-07-07 2021-07-07 142 149 10.22159/ijap.2021v13i4.41694 PRELIMINARY STUDY ON THE IMPACT OF POLYMER-LIPID TYPES AND RATIO TO POLYMERIC-LIPID HYBRID NANOPARTICLE <p><strong>Objective: </strong>This study aims to determine the best lipid to polymer ratios in polymeric-lipid nanoparticles using various types and ratios of polymers and lipids.</p> <p><strong>Method: </strong>Polymeric-lipid nanoparticle was prepared using the modified one-step nanoprecipitation method. This study used chitosan and Na alginate as polymers and lecithin and egg phosphatidylcholine as lipids. The lipid was crossed-combined with polymer in various ratios, i. e 12.5%, 25.0%, and 37.5%. On its preparation, <em>Cinnamomum burmanii</em> extract was loaded into the resulted polymeric-lipid nanoparticle as an active substance model. The results were assessed its particle surface characteristics including particle size, polydispersity index, and zeta potential.</p> <p><strong>Results: </strong>Twelve formulas resulted from crossed-combination between the lipid and polymer were used in this study. Polymeric-lipid nanoparticles resulted from the combination of egg phosphatidylcholine/Na alginate has particle size, polydispersity index, and zeta potential of 380.07±3.52 nm, 0.66±002, and-30.6±1.15 mV, respectively.</p> <p><strong>Conclusions: </strong>The best lipid to polymer ratio and type was observed in egg phosphatidylcholine: Na alginate. The particle surface characteristics were better compared to other combinations.</p> OKTAVIA EKA PUSPITA FERRI WIDODO MONICA ANDIKA PUTRI ISWA ROSSARIZA AVIOLA FADHILLA NI PUTU JUNITA SARI Copyright (c) 2021 Oktavia Eka Puspita, Ferri Widodo, Monica Putri, Iswa Rossariza, Aviola Fadhilla, Junita Sari Ni Putu 2021-07-07 2021-07-07 150 153 10.22159/ijap.2021v13i4.41663 BIOEQUIVALENCE STUDY OF AZELNIDIPINE 16 MG TABLET TO EVALUATE PHARMACOKINETIC PROFILE OF SINGLE DOSE IN HEALTHY, ADULT, HUMAN VOLUNTEERS UNDER FASTING CONDITION <p><strong>Objective: </strong>The present study's objective is to conduct a comparative bioavailability study with a special emphasis on the test product's bioequivalence using a standard reference product as a comparator.</p> <p><strong>Methods: </strong>Before initiating the bioequivalent study, the plasma sample analysis method was developed and validated by using LC-MS/MS method. The entire study was conducted as a single-dose crossover randomized bioequivalence study with open-label, two treatment, two-period, and two sequences on 24 healthy volunteers under fasting condition. With proper informed consent process the oral dose of the Reference product (R) or Test product (T) was administered on healthy volunteers at 0 h during each period of the study. After the drug's oral administration, a certain quantity of blood sample was collected, and the plasma sample was separated using a cold centrifuge. The plasma samples were analysed by using the validated LC-MS/MS method. The pharmacokinetic parameters, statistical data and ANOVA of the test and reference product were evaluated.</p> <p><strong>Results: </strong>The Cmax, Auc0-t, AUC0-∞ and t<sub>max</sub> of the test product were found to be 6.29 ng/ml, 117.0 ng. h/ml, 161.67 ng. h/ml and 3.33 h. respectively. And the Cmax, Auc0-t, AUC0-∞ and t<sub>max</sub> of reference product were found 6.59 ng/ml, 123.21 ng. h./ml, 172.20 ng. h/ml and 3.38 h respectively. Relative bioavailability was found 94.96%. The overall results show that the 90% confidence intervals (Log-Transformed and Untransformed) for Cmax, AUC0-t and AUC0-∞ for Azelnidipine were within the acceptable limit of 80%-125%.</p> <p><strong>Conclusion: </strong>The entire study's conclusion can be drawn as the test product was bioequivalent with the reference product's comparator.</p> DIBYA DAS DHIMAN HALDER ANIRBANDEEP BOSE CHIRANJIT SAHA HIMANGSHU SEKHAR MAJI TAPAN KUMAR PAL Copyright (c) 2021 DIBYA DAS 2021-07-07 2021-07-07 154 159 10.22159/ijap.2021v13i4.41331 STRUCTURAL DETERMINATION OF L-ASPARAGINASE II OF STREPTOMYCES ALBIDOFLAVUS AND INTERACTION ANALYSIS WITH L-ASPARAGINE AND CEFOTAXIME <p><strong>Objective: </strong>L-Asparaginase enzyme possesses a crucial role in the treatment of various hematologic malignancies. The current study focuses on homology modeling and interaction analysis of L-Asparaginase proteins belonging to <em>Streptomyces albidoflavus</em> (<em>S. albidoflavus</em>) with the essential ligand L-Asparagine and subsequent analysis with essential β-lactam antibiotic Cefotaxime.</p> <p><strong>Methods: </strong>The process of understanding Asparaginase interactions primarily involved structure determination of WP_096097608, WP_095730301, which is achieved by GalaxyTBM, I-TASSER and SWISS-MODEL. Further, the <em>S. albidoflavus</em> Asparaginase proteins are subjected to GalaxySite and Autodock Vina of PyRx analysis.</p> <p><strong>Results: </strong>The GalaxyTBM predicted structures of both the proteins are found promising on various validation studies. The two Asparaginase proteins exhibited high binding affinities of-6.8 and-6.5 kcal/mol with Cefotaxime and-5.1 and-4.9 kcal/mol towards Asparagine. The protein WP_096097608 residues forming hydrogen bonds with L-Asparagine are also analysed to involve in interaction with Cefotaxime on individual docking analysis.</p> <p><strong>Conclusion: </strong>The current findings details the two <em>S. albidoflavus</em> Asparaginase proteins affinity towards L-Asparagine, hence can be assessed further for immunogenicity studies. In addition to the above findings, an attempt is made to find the L-Asparaginase binding possibilities with non-metals that identified an essential β-lactam antibiotic Cefotaxime to be an effective inhibitor. This study helps in understanding the interactions of L-Asparaginase with Cefotaxime, as intake of antibiotics between the phases of chemotherapy is observed to treat various infections and also as an antibiotic to microbes that utilize Asparaginase as a vital enzyme.</p> ACHYUTUNI VENKATA NAGA TEJASWINI MALOTHU RAMESH Copyright (c) 2021 2021-07-07 2021-07-07 160 167 10.22159/ijap.2021v13i4.41303 DESIGN, OPTIMIZATION AND EVALUATION OF ACECLOFENAC FAST DISSOLVING TABLETS EMPLOYING STARCH VALERATE–A NOVEL SUPERDISINTEGRANT <p><strong>Objective: </strong>To synthesize, characterize and evaluate starch valerate as a superdisintegrant in the formulation of aceclofenac fast dissolving tablets by employing 2<sup>3</sup> factorial design.</p> <p><strong>Methods: </strong>Starch valerate was synthesized and its physical and micromeritic properties were performed to evaluate it. The fast dissolving tablet of aceclofenac was prepared by employing starch valerate as a superdisintegrant in different proportions in each case by direct compression method using 2<sup>3</sup> factorial design for evaluation of tablet parameters like disintegration and dissolution efficiency in 5 min.</p> <p><strong>Results: </strong>The starch valerate prepared was found to be fine, amorphous and free flowing. Starch valerate exhibited good swelling in water with swelling index (125.2%). The study of starch valerate was shown by fourier transform infrared spectra (FTIR). The drug content (200±5%), hardness (3.5–4 kg/sq. cm), and friability (&lt;0.15%) has been effective with regard to all the formulated fast dissolving tablets employing starch valerate. The disintegration time of all the formulated tablets was found to be in the range of 14±0.04 to 25.7±0.02 sec. The optimized formulation F4 had the least disintegration time i.e., 12.8±0.02 sec. The wetting time of the tablets was found to be in the range of 76±0.21 to 217±0.17s. The <em>In vitro</em> wetting time was less (i.e., 28±0.02s) in optimized formulation F4. The water absorption ratio of the formulated tablets was found to be in the range of 46±0.12 to 100±0.27%. The percent drug dissolved in the optimized formulation F8 was found to be 99.93% in 5 min.</p> <p><strong>Conclusion: </strong>Starch valerate, when combined with sodium starch glycolate, croscarmellose sodium, with aceclofenac, was found to be an effective super disintegrant which improved the dissolution efficiency and could therefore be used in the formulation of quick dissolving tablets to provide immediate release of the contained drug within 5 min.</p> R. SANTOSH KUMAR SHAMBHAVI KANDUKURI M. RAMYA B. KUSUMA LATHA Copyright (c) 2021 Santosh Kumar Rada 2021-07-07 2021-07-07 168 176 10.22159/ijap.2021v13i4.41122 RESVERATROL-HUMIC ACID LOADED COLLOIDAL POLYMERIC NANOPARTICLES: DESIGN OF EXPERIMENT AND IN VITRO EVALUATION <p><strong>Objective</strong><strong>:</strong> The study aims at fabrication and optimization of co-encapsulated resveratrol and humic acid in colloidal polymeric nanocarriers to improves the stability of insoluble antioxidant, resveratrol.</p> <p><strong>Methods: </strong>The Eudragit E100 polymeric material was used to fabricate oral co-encapsulation of resveratrol and humic acid in colloidal polymeric nanocarriers, called <em>Res</em>-HA-co-CPNs by an emulsification-diffusion-evaporation method. Taguchi orthogonal array design was employed to check the effect of formulation factors on <em>in vitro</em> physicochemical characteristics. The optimized formulation was further evaluated for stability studies at different conditions.</p> <p><strong>Results: </strong>Optimized <em>Res</em>-HA-co-CPNs demonstrated spherical and smooth surface including mean PS 120.56±18.8 nm, PDI 0.122, ZP+38.25mV, and EE 82.37±1.49%. Solid-state characterizations confirmed that optimized <em>Res</em>-HA-co-CPNs showed amorphous characteristics. <em>In vitro</em> release profile of <em>Res</em>-HA-co-CPNs showed an outstanding sustained release behavior up to 48h and remain stable at the refrigerated condition for 6 mo.</p> <p><strong>Conclusion: </strong><em>Res</em>-HA-co-CPNs would be a proficient and promising dosage form for increasing the stability of insoluble antioxidants, resveratrol.</p> RAHUL H. SUNDEEP C. SWATI G. Copyright (c) 2021 Dr Swati Gupta 2021-07-07 2021-07-07 177 184 10.22159/ijap.2021v13i4.41878 FABRICATION AND CHARACTERIZATION OF RALOXIFENE LOADED SOLID-LIPID NANOPARTICLES <p><strong>Objective:</strong>&nbsp; The poor water solubility of the drug presents a great challenge for the formulation development and results in low oral bioavailability. The oral bioavailability of Raloxifene HCl (RLX) is very low (&lt;2%) in humans due to its poor solubility. The objective of the present study was to develop RLX loaded solid-liquid nanoparticles for effective drug delivery<strong>.</strong></p> <p><strong>Methods:</strong> Compritol 888 ATO-based RLX-loaded solid lipid nanoparticles (SLNs) were formulated using the oil in water microemulsion method. Drug-excipients compatibility was confirmed through Fourier transform infrared spectroscopy, Differential scanning calorimetry methods. The SLN was characterized for particle size, surface morphology, entrapment efficiency.</p> <p><strong>Results:</strong> A total of seventeen formulations (SLN1-SLN17) were developed as per the 3 levels 3 factor Box–Behnken design. The model used for the analysis was statistically analyzed using ANOVA and the goodness of fit was evaluated using diagnostic plots. As per the response-surface plots, the amount of lipid, poloxamer 407, and ultrasonication time have a significant effect on the particle size and entrapment efficiency (%EE). The developed RLX-loaded SLNs have the size and %EE in the range of 165.63±2.62 nm to 315.33±4.87 nm and 75.21±2.32% to 95.32±2.11%. The TEM analysis showed that the developed RLX-loaded SLNs were almost spherical and has a small size range.</p> <p><strong>Conclusion: </strong>The high biocompatibility, biodegradability, ability to protect drugs in GIT, and sustained release properties make SLNs an ideal candidate to resolve poor oral bioavailability challenges.</p> NAVIN CHANDRA PANT VIJAY JUYAL Copyright (c) 2021 Navin Pant, Vijay Juyal 2021-07-07 2021-07-07 185 191 10.22159/ijap.2021v13i4.41774 DESIGN OF CONTROLLED RELEASE MUCOADHESIVE BUCCAL TABLETS OF IVABRADINE HCL USING SINTERING TECHNIQUE <p><strong>Objective: </strong>The objective of the present work was to study the use of the sintering technique, a relatively new concept in pharmaceutical sciences, in the development of mucoadhesive buccal tablets for ivabradine Hydrochloride.</p> <p><strong>Methods: </strong>The method consisted of blending drug, hydroxypropyl methylcellulose (HPMC K100M), carnauba wax, and other excipients followed by direct compression into tablets. The compressed fluffy matrices were sintered at two different constant temperatures like 50 °C and 60 °C for two different periods like 1.5 h and 3 h in a hot air oven. The effect of sintering on tensile strength, dissolution profile, and other parameters were studied. The drug-polymer-excipient compatibility was evaluated by Fourier transform Infrared (FTIR) and differential scanning calorimetric<strong> (</strong>DSC) studies.</p> <p><strong>Results: </strong>The sintering condition markedly affected the drug release properties, hardness, and friability of the tablets. Based on the f<sub>2</sub> similarity factor value, <em>Ex-vivo</em> mucoadhesive strength, <em>Ex-vivo</em> residence time, and <em>in vitro</em> dissolution studies, formulation F3SD was selected as an optimized formulation. Drug release followed a non-Fickian diffusion mechanism with the Higuchi model release kinetics. Stability studies of mucoadhesive buccal tablets in normal human saliva indicated the stability of the drug and buccal tablet in the oral cavity. Stability studies as per ICH guidelines revealed that optimized formulation was stable on storage conditions.</p> <p><strong>Conclusion: </strong>The sintering technique provides a significant and convenient method for the development of a controlled release dosage form that can be used in the design of mucoadhesive buccal tablets of Ivabradine HCL.</p> CHANDAN MOHANTY K. V. SUBRAHMANYAM Copyright (c) 2021 Chandan Mohanty, K V SUBRAHMANYAM 2021-07-07 2021-07-07 192 203 10.22159/ijap.2021v13i4.41931 METHOD DEVELOPMENT AND VALIDATION OF THE CHROMATOGRAPHIC ANALYSIS OF FLUTICASONE PROPIONATE AND SALMETEROL XINAFOATE COMBINATION IN SOLUTIONS AND HUMAN PLASMA USING HPLC WITH UV DETECTION <p><strong>Objective: </strong>A simple, Rapid, and sensitive HPLC method utilizing UV detection was developed and validated for the simultaneous estimation of Fluticasone propionate (FP) and Salmeterol xinafoate (SX) in solutions and <em>in vitro</em> human plasma.</p> <p><strong>Methods: </strong>Chromatographic analysis was done on SUPELCO<sup>®</sup> RP-C18 column (150 x 4.6 mm, 5 μm particle size) with an isocratic mobile phase composed of methanol, acetonitrile, and water (50:20:30, v/v) mixture while flow rate was set to 1 ml/min. Detection with UV at maximum absorbance wavelength (ʎ<sub>max</sub>) values of 236 and 252 for FP and SX, respectively. Spiked plasma samples were liquid-liquid extracted by diethyl ether and reconstituted using methanol.</p> <p><strong>Results: </strong>Method was accurate and precise over a linear (R<sup>2</sup>&gt;0.995) range of (0.067-100 µg/ml) and (0.0333-50 µg/ml) for FP and SX, respectively. LOD/lOQ values were 0.13/0.6 and 0.06/0.3 µg/ml for FP and SX, respectively.</p> <p>The developed method was successfully applied for the analysis of FP and SX in spiked human plasma samples. The method is considered to be accurate and precise over a linear (R<sup>2</sup>&gt;0.9969) range of (6.67-66.67 µg/ml) and (3.33-33.3 µg/ml) for FP and SX, respectively. Extraction efficiency was approved by recovery values of (94.98–102.46 %) and (96.54–102.62 %) for FP and SX, respectively.</p> <p><strong>Conclusion</strong>: This validated method revealed simple and cheap extraction procedures and detectors, non-buffered mobile phase, and short retention times with excellent resolution.</p> MOHAMMAD JAMAL A. SHAMMOUT HAMMAM B. YOUSEF KHALID H. ABU-SHANDI MOHAMMAD I. ALOMARI MOHAMMAD R. HASAN ATEF O. AL-OTHMAN WALEED A. MANASREH Copyright (c) 2021 Mohammad Jamal Shammout, Khalid Abu-Shandi, Hammam Bahjat Yousef, Mohammad I. Alomari, Mohammad R. Hasan, Atef O. Al-Othman, Waleed A. Manasreh 2021-07-07 2021-07-07 204 210 10.22159/ijap.2021v13i4.41678 FORMULATION DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM BY ZAFIRLUKAST <p><strong>Objective: </strong>The main objective of the present study was to formulate and evaluate a time-controlled single-unit oral pulsatile drug delivery system containing Zafirlukast for the prevention of nocturnal asthma attacks. To provide time-scheduled drug release for Asthma disease. It is used for preventing asthmatic attacks at early morning. Pulsatile release dosage form is increasing patient compliance by reducing the dosing frequency, especially in the early morning.</p> <p><strong>Methods: </strong>Core tablets were prepared by incorporating different concentrations of natural and synthetic super disintegrants. Drug-containing core tablets (ZC1-ZC15) with different compositions of natural super disintegrants (Plantago ovata seed powder, Locust bean gum) synthetic super disintegrants (Sodium starch glycolate (SSG), Cross carmellose sodium (CCS), Crospovidone (CP)) were prepared by direct compression technique. The core tablets were subjected to pre-formulation, physicochemical and <em>In vitro</em> drug release studies. The fast disintegrating core tablet formulation was selected and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic polymers Eudragit RS100, Eudragit RL 100, Ethylcellulose and hydrophilic polymers Hydroxypropyl methylcellulose K4M, K100M. The optimized formulation was selected and quantified based on <em>in vitro</em> drug release profile in simulated gastric and intestinal fluids.</p> <p><strong>Results: </strong>The pre and post-compression parameters of tablets were also found to be within limits. Formulation ZC5 with 16 mg of Locust bean gum showed the least disintegrating time, i.e., 22.13 sec, and was selected as the best immediate release core tablet. The press-coated tablet formulation P8 having 62.5 mg Eudragit RS100 and 62.5 mg of HPMC K4M in ratio 1:1 over the core tablet ZC5 showed rapid and drug release nearly after 4 h lag time and 98.86 % up to 12 h. Accelerated stability studies of the optimized formulation P8 indicated no significant difference in release profile after 3 mo.</p> <p><strong>Conclusion: </strong>The&nbsp;<em>in vitro</em>&nbsp;dissolution study showed that lag time before drug release was highly affected by the coating amount level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.</p> N. SHIVA KRISHNA B. JAYANTHI A. MADHUKAR Copyright (c) 2021 Ramya 2021-07-07 2021-07-07 211 220 10.22159/ijap.2021v13i4.41734 FORMULATION AND EVALUATION OF SUSTAINED-RELEASE PELLETS OF LORNOXICAM <p><strong>Objective: </strong>The aim of the study was to develop sustained release pellets of lornoxicam using Eudragit RLPO and Eudragit RSPO to reduce the dosing frequency.</p> <p><strong>Methods: </strong>The sustained release pellets of lornoxicam were prepared by extrusion–spheronization technique using Eudragit RLPO and Eudragit RSPO as release retardant polymers and microcrystalline cellulose as spheronizing agent. A 3<sup>2</sup> Full factorial design was applied to investigate the combined effect of the two independent variables i.e. concentration of Eudragit RLPO (X<sub>1</sub>) and concentration of Eudragit RSPO (X<sub>2</sub>) on the dependent variables, <em>In vitro</em> drug release at 1h (Y<sub>1</sub>), <em>In vitro</em> drug release at 4 h (Y<sub>2</sub>) and <em>In vitro</em> drug release at 12 h. (Y<sub>3</sub>).</p> <p><strong>Results: </strong>The optimized formulation (F0) show <em>in vitro</em> drug release 11.24±1.21 %, 43.69±1.28 %, 82.69±1.74 % and 100.24±1.56 % at 1 h, 4 h, 12 h and 24 h respectively. Drug excipients compatibility study by FTIR showed no interaction between drug and excipients. Eudragit RLPO and Eudragit RSPO had a significant effect on <em>in vitro</em> drug release.</p> <p><strong>Conclusion: </strong>From all parameters and experimental design evaluation, it was concluded that the drug release rate decreased with an increase the concentration of Eudragit RLPO and Eudragit RSPO. SEM Photomicrograph of pellets revealed that the surface was rough and the pellets were spherical shaped in nature. The <em>in vitro</em> release kinetics revealed higuchi model is followed and drug release is by anamolous diffusion.</p> MILIND J. AMIN KEYUR S. PATEL DEEPA R. PATEL ZIL P. PATEL JAYANTI V. BAJAG Copyright (c) 2021 Dr. Keyur S. Patel 2021-07-07 2021-07-07 221 227 10.22159/ijap.2021v13i4.41601 A NOVEL NANOGEL FORMULATION OF FINASTERIDE FOR TOPICAL TREATMENT OF ANDROGENETIC ALOPECIA: DESIGN, CHARACTERIZATION AND IN VITRO EVALUATION <p><strong>Objective</strong>: The present paper describes the development and evaluation of a Novel Finasteride (FSD) nanogel topical delivery for the treatment of Androgenetic Alopecia. Nano-based topical formulation was chosen to enhance the solubility, permeability, biocompatibility of drug and to overcome the problems associated with the oral delivery of finasteride.</p> <p><strong>Methods</strong>: Various trails batches were prepared by using probe sonication method. Based on stability studies and particle size, NP4 trail was optimized which exhibited a spherical shape with a mean diameter of 113.80±0.72, the polydispersity of 0.28±0.01, zeta potential of-25.2 mV, drug entrapment efficiency of 92.67±0.47 %, and drug loading of 6.15±0.02 %. Storage stability studies demonstrated that the particle size and entrapment efficiency were not changed during 3 mo both at 4 °C and room temperature. Finasteride (FSD) NLCs were characterized for particle size by scanning electron microscope (SEM), chemical state by X-Ray diffraction (XRD), physical stability by centrifugation and thermodynamic stability by Freeze-thaw method. These prepared nanoparticles were transformed into topical nanogel and further evaluated.</p> <p><strong>Results</strong>: Among the different trails, C2 trail of NLC gel has shown excellent gelling capacity, clear appearance, good viscosity characteristics and was selected for further evaluation studies. Batches of topical nanogel were characterized through pH, homogeneity, spreadability, viscosity, drug content and <em>in vitro</em> drug release study. Based on pH (6.5-6.8), drug content (91.25±0.9%), spreadability (6.7 cm/sec), C2 batch was subjected to <em>In vitro</em> skin occlusivity study, in-vitro release study and <em>In vitro</em> heamolysis study.</p> <p><strong>Conclusion</strong>: The percent cumulative drug release for Finasteride (FSD) gel was found to be 758.52±1.49 µg at 24 h which is quite higher than plain gel and Finasteride (FSD) gel showed maximum occlusiveness and excellent spreadability and found to be stable. In conclusion, prepared Finasteride (FSD) Nanogel could be used with promising potential for the treatment of Androgenetic Alopecia.</p> DIVYA SANGANABHATLA R. SHYAM SUNDER Copyright (c) 2021 Divya sanganabhatla 2021-07-07 2021-07-07 228 240 10.22159/ijap.2021v13i4.41599 STATISTICALLY OPTIMIZED AND BOX-BEHNKEN DESIGN ASSISTED METHOD DEVELOPMENT AND VALIDATION OF AN ANTIPSYCHOTIC MEDICATION OLANZAPINE AND ITS RELATED IMPURITIES BY REVERSE-PHASE HPLC-UV SPECTROSCOPY <p><strong>Objective: </strong>Statistically designed and Box-Behnken design (BBD) assisted reversed-phase high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated for the identification of an antipsychotic medication Olanzapine and its organic impurities in pure drug along with forced degradation studies.</p> <p><strong>Methods: </strong>The present developed method employed BBD optimized chromatographic conditions comprising of an Inertsil ODS 3V analytical column with dimension 250 mm x 4.6 mm and particle size 5µ. The isocratic mobile phase was used as a mixture of monobasic sodium phosphate buffer (0.01 M, pH 6), methanol and acetonitrile in the proportion of 40/30/30, v/v. The mobile phase flow rate and UV λmax was 1 ml/min and 260 nm, respectively. The method was optimized by Box-Behnken design using design expert software, comprising of three factors for Olanzapine for instance flow rate (A), mobile phase composition (B) and pH (C) while resolution between Olanzapine related compound A and Olanzapine related compound B (Y<sub>1</sub>) and tailing of Olanzapine (Y<sub>2</sub>) were taken as a response.</p> <p><strong>Results: </strong>Application of BBD yielded statistically designed method with excellent quality parameters achieved in terms of linearity with the coefficient of correlation (R<sup>2</sup>&gt;0.9999), limit of detection (LOD, 0.0023-0.16 µg/ml), the limit of quantification (LOQ, 0.007-0.39 µg/ml), accuracy (99-100%) and precision ((2%, relative standard deviation (%RSD) were evaluated as per latest available procedures.</p> <p><strong>Conclusion: </strong>Forced degradation conditions were carried out, demonstrated that the optimized method was stable and no any interfering peaks eluting at the similar retention time of the studied compounds. The method was found to be stable, easy, rugged and robust, could be applied for the similar types of the pure drug.</p> MD IRSHAD ALAM AQUIL-UR-RAHIM SIDDIQUI Copyright (c) 2021 Md Irshad Alam 2021-07-07 2021-07-07 241 246 10.22159/ijap.2021v13i4.41427 OPTIMIZATION OF STARCH CROTONATE AS A NOVEL SUPERDISINTEGRANT IN THE FORMULATION OF FAST DISSOLVING TABLETS THROUGH 23 FACTORIAL DESIGN <p><strong>Objective: </strong>To synthesize, characterize and evaluate starch crotonate as a superdisintegrant in the formulation of Piroxicam fast dissolving tablets by employing 2<sup>3</sup> factorial design.</p> <p><strong>Methods: </strong>Starch crotonate was synthesized and its physical and micromeritic properties were performed to evaluate it. The fast dissolving tablet of Piroxicam were prepared by employing starch crotonate as a superdisintegrant in different proportions in each case by direct compression method using 2<sup>3</sup> factorial design.</p> <p><strong>Results: </strong>The starch chrotonate prepared was found to be fine, free flowing and amorphous. Starch crotonate exhibited good swelling in water with swelling index (50%). The study of starch crotonate was shown by fourier transform infrared spectra (FTIR). The drug content (100±5%), hardness (3.6–4 kg/sq. cm), and friability (&lt;0.15%) have been effective with regard to all the formulated fast dissolving tablets employing starch crotonate. The disintegration time of all the formulated tablets was found to be in the range of 18±03 to 66±03 sec. The optimized formulation F8 had the least disintegration time i.e., 18±03 sec. The wetting time of the tablets was found to be in the range of 49.92±0.11 to 140±0.18s. The <em>In vitro</em> wetting time was less (i.e., 74±0.37s) in optimized formulation F8. The water absorption ratio of the formulated tablets was found to be in the range of 27.58±0.01 to 123.07±0.33%. The percent drug dissolved in the optimized formulation F8 was found to be 99.83% in 10 min.</p> <p><strong>Conclusion: </strong>Starch crotonate, when combined with sodium starch glycolate, croscarmellose sodium, with Piroxicam was found to be an effective super disintegrant which improved the dissolution efficiency and could therefore be used in the formulation of quick dissolving tablets to provide immediate release of the contained drug within 10 min.</p> A. HARI OM PRAKASH RAO SANTOSH KUMAR RADA SHAMBHAVI KANDUKURI Copyright (c) 2021 Santosh Kumar Rada 2021-07-07 2021-07-07 247 256 10.22159/ijap.2021v13i4.41335 ENHANCEMENT OF THERAPEUTIC WINDOW OF METFORMIN HYDROCHLORIDE BY FABRICATION OF MICROSPHERES COMPRISING POLYMERIC INCULCATION WITH SEMI-SYNTHETIC AND SYNTHETIC POLYMERS BY IMPLEMENTATION OF BOX-BEHNKEN DESIGN <p><strong>Objective: </strong>Innovative enhancement of therapeutic window of Metformin hydrochloride (MFH) and bioavailability through mucoadhesive microspheres by polymeric inculcation of hydroxypropyl methylcellulose K4M grade (HPMC K4M), hydroxypropyl methylcellulose K100M grade (HPMC K100M) and Kollidon SR grade (KS).</p> <p><strong>Methods: </strong>Controlled release system was developed by incorporating semi-synthetic and synthetic polymers by modified solvent evaporation technique. Fabrication of mucoadhesive microspheres was designed by the implementation of experimental designs to obtain most optimum concentration of selected factors. The method was optimized by Box Behnken design (BBD) with selected factors as concentrations of semi-synthetic and synthetic polymer with stirring speed influence for the obtained responses that were mean particle size (Y1) entrapment efficiency of drug (Y2) and percent mucoadhesion (Y3). Microspheres were characterized for particle size, entrapment efficiency of drug, ex-vivo mucoadhesion study, <em>in vitro</em> study, Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD) detection and H<sup>1</sup> Nuclear magnetic resonance (NMR) quantification for optimized formulation.</p> <p><strong>Results: </strong>Implementation of response surface method software for BBD yielded stable microspheres with mean particle size 274 µm, entrapment efficiency of drug 85.07% and percent mucoadhesion 67.03% for optimized formulation F5.</p> <p><strong>Conclusion: </strong>Bridging of MFH with the highly innovative combination of semi-synthetic and synthetic polymers yielded stable, cost-effective microspheres with improved bioavailability with controlled-release effect as till date no literature is available that provide information with selected polymeric combination and analytical characterization.</p> MD AAMER QUAZI NAZIA KHANAM Copyright (c) 2021 NAZIA KHANAM, MD AAMER QUAZI 2021-07-07 2021-07-07 257 264 10.22159/ijap.2021v13i4.41225 STABILITY INDICATIVE AND COST EFFECTIVE ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF FAVIPIRAVIR AND PERAMIVIR IN BULK AND PHARMACEUTICAL DOSAGE FORM BY USING RP-HPLC <p><strong>Objective: </strong>The current investigation was pointed at developing and progressively validating novel, simple, responsive and stable RP-HPLC method for the measurement of active pharmaceutical ingredients of Favipiravir and Peramivir and their related substances.</p> <p><strong>Methods: </strong>A simple, selective, validated and well-defined stability that shows gradient RP-HPLC methodology for the quantitative determination of Favipiravir and Peramivir. The chromatographic strategy utilized Inertsil ODS column of dimensions 250x4.6 mm, 5 micron, using isocratic elution with a mobile phase of acetonitrile and 0.1 percent orthophosphoric acid (70:30). A flow rate of 1 ml/min and a detector wavelength of 260 nm utilizing the PDA detector was given in the instrumental settings. Using the impurity-spiked solution, the chromatographic approach was streamlined.</p> <p><strong>Results: </strong>Validation of the proposed method was carried out according to an international conference on harmonization (ICH) guidelines. LOD and LOQ for the two active ingredients and their impurities were established with respect to test concentration. The calibration charts plotted were linear with a regression coefficient of R<sup>2</sup>&gt;0.999, which means the linearity was within the limit. Recovery, specificity, linearity, accuracy, robustness, ruggedness was determined as a part of method validation and the results were found to be within the acceptable range.</p> <p><strong>Conclusion: </strong>The proposed method to be fast, simple, feasible and affordable in RS condition. During stability tests, it can be used for routine analysis of production samples and to verify the quality of drug samples during stability studies.</p> SRINIVAS LINGABATHULA NEELU JAIN Copyright (c) 2021 SRINIVAS L, Neelu Jain 2021-07-07 2021-07-07 265 271 10.22159/ijap.2021v13i4.40530 FLUCONAZOLE NANOGEL: FABRICATION AND IN VITRO EVALUATION FOR TOPICAL APPLICATION <p><strong>Objective</strong>: The aim of this study is to develop and <em>in vitro</em> evaluation of prepared fluconazole nanogel for seborrheic dermatitis</p> <p><strong>Methods</strong>: Fluconazole nanogel was formulated to act against seborrheic dermatitis. The fluconazole nanoparticles were prepared by a simplified evaporation method and evaluated for particle size, entrapment efficiency, and percent <em>in vitro</em> drug release. The nanogel was also characterized based on parameters like particle size, percent entrapment efficiency, shape surface morphology, rheological properties, <em>in vitro</em> release <em>R² = 0.9046</em>, and release kinetics.</p> <p><strong>Results</strong>: The nanoparticle with a combination of Eudragit RS and Tween 80 showed the best result with particle size in the range of 119.0 nm to 149.5 nm, with a cumulative percent drug release of 95 % up to 18 h. The formulated nanogel with optimum concentration of HPMC authenticate with particle size 149.50±0.5 with maximum drug release (92.13±0.32) %.</p> <p><strong>Conclusion</strong>: Different percentages of polymers (ethyl-cellulose, eudragit, and tween 80) are used as variable components in the formulation of nanogel. The optimized batch showed good physical properties (flow index, spreadability, and viscosity) along with rapid drug release. Therefore, it can be concluded that nanogel containing fluconazole has potential application in topical delivery.</p> DIVYA INDERBIR SINGH UPENDRA NAGAICH Copyright (c) 2021 Divya, Inderbir singh, Upendra Nagaich 2021-07-07 2021-07-07 272 277 10.22159/ijap.2021v13i4.40531 MYRICETIN NANO-PHYTOSOMES PEEL-OFF GEL MASK FORMULATION AS ANTIOXIDANT <p><strong>Objective: </strong>Peel-off gel mask is an alternative preparation which can increase the convenience of use and is expected to increase the antioxidant activity of myricetin nano-phytosomes<em>. </em>Myricetin has various activities, namely as a natural antioxidant, anti-inflammatory, allergy, and anti-cancer. This study aims to determine the nano-phytosome myricetin can be formulated into a gel peel-off mask, determine the concentration of PVA which has the best physical properties of the gel peel-off mask, and determine the antioxidant activity.</p> <p><strong>Methods: </strong>The thin layer hydration method was used to manufacture Myricetin nano-phytosomes, then dried using the freeze-drying method. The resulting nano-phytosome characterization included particle size, polydispersion index, zeta potential and absorption efficiency. Peel-off gel mask were made with variations in the concentration of the PVA gelling agent, namely F1 3.5%, F2 7%, F3 14%. The resulting peel-off gel mask was tested for physical quality including organoleptic test, homogeneity, pH, viscosity, adhesion, drying time and testing for antioxidant activity.</p> <p><strong>Results: </strong>The resulting peel-off gel mask has the good physical quality and met the existing requirements, where the different PVA concentrations resulted in different physical qualities, the higher the PVA, the faster the dry time. All three formulas exhibited very strong antioxidant activity based on DPPH assay with IC<sub>50</sub> value of 14.8 ppm (F1), 15.37 ppm (F2), and 15.87 ppm (F3).</p> <p><strong>Conclusion: </strong>Myricetin nano-phytosomes can be formulated into a gel peel-off mask, Formula 2 with a 7% concentration of PVA produces the best physical quality of the peel-off gel mask, the three gel peel-off mask formulas have excellent antioxidant activity.</p> NUR AINI DEWI PURNAMASARI MUHAMMAD DZAKWAN GANET EKO PRAMUKANTORO RACHMAT MAULUDIN ELFAHMI Copyright (c) 2021 Nur Aini Dewi Purnamasari 2021-07-07 2021-07-07 278 281 10.22159/ijap.2021v13i4.40376 EFFECT OF STERILIZATION USING GAMMA RADIATION ON THE PHYSICOCHEMICAL PROPERTIES OF GEL CONTAINING ALOE VERA POWDER <p><strong>Objective: </strong>This study aims to prepare sterile gel containing aloe vera (AV) powder and evaluate its physicochemical properties after sterilization by gamma radiation.</p> <p><strong>Methods: </strong>The gel was prepared using carbomer as stabilizer, and sterilized by gamma radiation. The physical stability was evaluated including organoleptic, pH, viscosity and sterilization. Furthermore, malic acid concentration was determined as a marker compound contained in the gel.</p> <p><strong>Result</strong><strong>s</strong><strong>:</strong> The gel was successfully prepared containing 20% AV powder and 25% carbomer. The physical properties including organoleptic, pH and viscosity were not significantly changed after sterilization, and also stable even after 28 storage days. Meanwhile, malic acid concentration before and after sterilization were 47.2 mg/ml and 43.9 mg/ml, respectively. This showed the physicochemical properties were not significantly different after sterilization.</p> <p><strong>Conclusion: </strong>Gamma radiation is suitable to sterilize gel containing AV powder.</p> ARIF BUDIMAN Copyright (c) 2021 ARIF BUDIMAN 2021-07-07 2021-07-07 282 285 10.22159/ijap.2021v13i4.41771 MULTI-FUNCTIONAL CARBON DOTS: A SYSTEMATIC OVERVIEW <p>Carbon dots (CDs) have emerged as a potential material in the multifarious fields of biomedical applications due to their numerous advantageous properties including tunable fluorescence, water solubility, biocompatibility, low toxicity, small size and ease of modification, inexpensive scale-up production, and versatile conjugation with other targeted nanoparticles. Thus, CDs became a preferable choice in various biomedical applications such as nanocarriers for drugs, therapeutic genes, photo sensitizers, unique electronic, fluorescent, photo luminescent, chemiluminescent, and electro chemiluminescent, drug/gene delivery and optoelectronics properties are what gives them potential in sensing and antibacterial molecules. Further, their potentials have also been verified in multifunctional diagnostic platforms, cellular and bacterial bio-imaging, development of nanomedicine, etc. This present review provides a concise insight into the progress and evolution in the field of carbon dots research with respect to synthesis methods and materials available in bio-imaging, theranostic, cancer, gene therapy, diagnostics, etc. Further, our discussion is extended to explore the role of CDs in nanomedicine and nano theranostic, biotherapy which is the future of biomedicine and also serves to discuss the various properties of carbon dots which allow chemotherapy and gene therapy to be safer and more target-specific, resulting in the reduction of side effects experienced by patients and also the overall increase in patient compliance and quality of life and representative studies on their activities against bacteria, fungi, and viruses reviewed and discussed. This study will thus help biomedical researchers in percuss the potential of CDs to overcome various existing technological challenges.</p> MUTHADI RADHIKA REDDY KUMAR SHIVA GUBBIYAPPA Copyright (c) 2021 muthadi radhika reddy 2021-07-07 2021-07-07 1 22 10.22159/ijap.2021v13i4.41002 EXOSOME NANOCARRIERS: BASIC BIOLOGY, DIAGNOSIS, NOVEL AND PERSPECTIVE APPROACH IN DRUG DELIVERY SYSTEMS: A REVIEW <p>Exosomes are the extracellular vesicles surrounded by a phospholipid bilayer shed from all cell varieties and plays a significant role in the communication and Transportation of materials between the cells due to their ability to transfer the proteins and nucleic acids from One cell to the another cell. Analogous in size and performance to synthetic nanoparticles, exosomes provide several Advantages, rendering them the foremost promising candidates for targeted drug or gene delivery vehicles. This review highlights the isolation techniques and delivery potential of exosomes, and equally presents research or analysis gaps for enhancing the use of natural vesicles for delivery functions. Exosome-based drug formulations can be applied to an extensive variety of diseases such as various infectious, cardiovascular, cancer and neurodegenerative disorders. Mostly, exosomes combine the benefits of both synthetic nanocarriers and cell-mediated drug delivery systems however avoiding their limitations.</p> P. V. KAMALA KUMARI KETHA SRILEKHYA K. BHAVYA SINDHU Y. SRINIVASA RAO Copyright (c) 2021 Kamala Kumari Paravastu 2021-07-07 2021-07-07 23 30 10.22159/ijap.2021v13i4.40842 RECENT STRATEGIES FOR IMPROVING SOLUBILITY AND ORAL BIOAVAILABILITY OF PIPERINE <p>Piperine, the main bioactive compound found in black pepper (<em>Piper nigrum</em> L.), has long been used in Ayurveda and traditional Chinese medicine (TCM). This compound has remarkable potential pharmacological properties, including being anti-inflammatory, antimicrobial, anticancer, anticonvulsant, antidepressant, neuroprotective, and hepatoprotective. Recent studies have reported piperine activity as an antiviral against SARS-CoV-2, which caused COVID-19. Nevertheless, the clinical use of piperine is still limited, due to its poor water solubility and bioavailability; therefore, various approaches have been developed in order to solve these limitations. This review summarises recent studies (i.e. uploaded to electronic databases in the last 10 y) regarding strategies that have been investigated to improve piperine’s solubility and pharmacokinetic properties, using ‘piperine’, ‘solubility’, ‘bioavailability’, and ‘formulation’ as keywords. Articles that have focused on piperine as the main compound were selected and sorted based on their modification and formulation types. Studies reported various approaches: from derivatives and analogue synthesis, crystal engineering, complexation, particle size reduction (micro-and nanonisation), and lipid-and polymer-based drug delivery systems, to inorganic and hybrid nanoparticles. This review also highlights limitations and challenges for these approaches and encourages further studies to optimise piperine’s potential benefits.</p> HULWA SALSABILA LILI FITRIANI ERIZAL ZAINI Copyright (c) 2021 Erizal Zaini, Hulwa Salsabila, Lili Fitriani 2021-07-07 2021-07-07 31 39 10.22159/ijap.2021v13i4.41596 RECENT APPROACHES INVOLVED IN COLONIC DRUG TARGETING FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE: A REVIEW <p>The objective of the review is to present the contemporary approaches involved in colonic drug targeting for the therapy of inflammatory bowel disease (IBD). The adverse reactions and side-effects of the conventional drug delivery systems are largely on account of the systemic absorption of the drugs from the small intestine. Moreover, in current drug delivery systems, the drug has to be frequently administered and also in larger doses which greatly reduces patient compliance. Various approaches which are being described here mainly target the colonic region specifically for improved therapy of IBD, by increasing localization and accessibility of the drug to the target site. Also, these approaches will result in the reduction of dose and minimization of adverse effects combined with the use of conventional drug delivery systems.</p> SWAMINATHAN V. VAIYANA RAJESH C. Copyright (c) 2021 Swaminathan V, Vaiyana Rajesh 2021-07-07 2021-07-07 40 46 10.22159/ijap.2021v13i4.40893 METHODS FOR IMPROVING ALPHA-MANGOSTIN SOLUBILITY: A REVIEW <p>Solubility is an important parameter to achieve for the bioavailability of a drug to reach the therapeutic windows. <em>Garcinia mangostana</em> Linn is a plant with great potency for the development of natural medicine. Alpha-mangostin is one of the secondary metabolites of <em>G. mangostana</em> and has been reported to have several pharmacological activities. The Biopharmaceutics Classification System (BCS) is a system that classifies drugs based on their solubility and permeability. Due to its low solubility but high permeation, alpha-mangostin is categorized into class II of the Biopharmaceutics Classification System. Therefore, the determination of dosage forms and modification of solubility enhancers is limited due to its physical properties, as mentioned above. This disadvantage requires new methods to improve its solubility to administer alpha-mangostin, especially for oral administration. Here, we discuss the development of the methods to increase alpha-mangostin solubility to be applied to formulate a dosage form to reach a useful plasma level for medication.</p> NURUL FAJERIYATI MUCHTARIDI MUCHTARIDI IYAN SOPYAN Copyright (c) 2021 Nurul Fajeriyati 2021-07-07 2021-07-07 47 54 10.22159/ijap.2021v13i4.39065 PHARMACOTECHNICAL DEVELOPMENT AND OPTIMIZATION OF MULTILAYERED TABLETS: AN UPDATED INDUSTRIAL REVIEW WITH EMPHASIS ON BILAYER TABLETS <p>Fixed-dose combination formulations are multilayered platforms designed for solving complex medication regimens and overcoming polypharmacy problems especially in chronic diseases with geriatric patients. Multilayered tablets are considered promising avenues to combine different active pharmaceutical ingredients (APIs) for a synergic therapeutic effect, or different formulations of the same API in order to achieve a specific drug release profile. Besides, multilayered tablets can extensively help in avoiding possible interactions between different drugs, as well as optimizing each formulation individually in terms of pharmacokinetics and manufacturability. This review article discusses the most suitable materials used in the manufacturing of multilayered tablets, describes novel approaches to manufacturing improvement and process parameters, the influence of process parameters on layer adhesion, and the characterization tests of multilayered tablets.</p> AHMED M. AGIBA SOHA SAYED ABUL-ELLA REHAB A. ABD EL-MONEM Copyright (c) 2021 Ahmed M. Agiba, Soha Sayed Abul-Ella, Rehab A. Abd El-Monem 2021-07-07 2021-07-07 55 64 10.22159/ijap.2021v13i4.41528 DEUTERIUM AS A TOOL FOR CHANGING THE PROPERTIES OF PHARMACEUTICAL SUBSTANCES (REVIEW) <p>The review is devoted to the influence of the hydrogen isotope–deuterium on biological models of organisms and the biological activity of pharmaceutical substances.</p> <p>The positions of the influence of deuterium on the properties of active pharmaceutical ingredients and excipients are examined from different perspectives. The first position reflects an increase in the kinetic isotope effect (KIE) in processes involving known pharmaceutical substances in aqueous solutions with a deuterium/protium ratio (D/H) below natural. For the first time, the dose-response diagram shows the identity of deuterium with essential trace elements, when a deficiency and excess of an element reduces the organism's vitality. Improved kinetic characteristics are demonstrated for the molecular and organism levels of different hierarchical gradations. In particular, they consist in the possibility of increasing the dissolution rate of substances by influencing the carbohydrate mutarotation processes and the optical activity of chiral substances, increased accumulation of essential elements in medicinal plants and other processes associated with a possible change in metabolic pathways in the cell and the organism as a whole.</p> <p>The second considered position of the influence of deuterium is associated with the use of deuterated substances–new compounds or obtained by substitution of protium in known protium analogues. The KIE is presented, which is expressed in a decrease in the biotransformation rate as a result of deuteration, it allows predicting a rapid development of the new direction in the development of drugs. Having an identical therapeutic effect, deuterated analogs provide improved pharmacokinetic characteristics, such as reduced toxicity, blocked epimerization of optically active substances, and a change in the mechanisms of biotransformation. The obtained results make it possible to predict the mechanisms of the effect of deuterium on the biochemical transformations of pharmaceutical substances in the organism.</p> ANTON V. SYROESHKIN TATYANA V. PLETENEVA ELENA V. USPENSKAYA OLGA V. LEVITSKAYA IRINA V. TARABRINA SVITLANA N. NOVIKOVA IGOR A. ZLATSKIY Copyright (c) 2021 A.V. Syroeshkin , T.V. Pleteneva , I.A. Zlatskiy 2021-07-07 2021-07-07 65 73 10.22159/ijap.2021v13i4.41818 THE EFFICACY OF COVID-19 VACCINE AND THE CHALLENGE IN IMPLEMENTING MASS VACCINATION IN INDONESIA <p>Novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 2,38 million deaths and more than 108 million cases confirmed in one year of the pandemic are massive upheavals in social life and economy in the international world. An effective vaccine is needed to prevent further morbidity and mortality. This research aims to identify the challenge in implementing mass vaccination in Indonesia which is related to the efficacy of the COVID-19 vaccine. We retrieve sources from relevant and published articles in Google Scholar, Pubmed, DOAJ and Science Direct of articles up to January 2021. The keywords used for gathering information were listed below. Vaccine efficacy is defined as the proportional reduction of a disease case in a group of vaccinated participants compared with unvaccinated participants. The study of vaccine efficacy is a cohort study that is an important vaccine trial method in the field. It is conducted randomly on a large scale by using a control-placebo. During the trials, the country which used the vaccine needs to maintain and observe the vaccine epidemiology. A trial roadmap is expected to identify the condition of the area epidemiologically. Vaccine efficacy is essential to be observed before implementing the vaccine in society. However, intensive socialization about the advantage of vaccines is mainly needed to prevent irrelevant information in social media about mass vaccination.</p> I. KETUT TUNAS DEWA AYU AGUS SRI LAKSEMI I. PUTU EKA WIDYADHARMA LUH PUTU RATNA SUNDARI Copyright (c) 2021 I Ketut Tunas, Dewa A. A. S. Laksemi, I Putu Eka Widyadharma, Luh Putu Ratna Sundari 2021-07-07 2021-07-07 74 76 10.22159/ijap.2021v13i4.41270 APPLICATION OF 3D PRINTING IN INNOVATED DRUG DELIVERY: A REVIEW <p>Increasing requests for modified and personalized pharmaceutics and medical materials makes the implementation of additive manufacturing increased rapidly in recent years. 3D printing has been involved numerous advantages in case of reduction in waste, flexibility in the design, and minimizing the high cost of intended products for bulk production of. Several of 3D printing technologies have been developed to fabricate novel solid dosage forms, including selective laser sintering, binder deposition, stereolithography, inkjet printing, extrusion-based printing, and fused deposition modeling. The selection of 3D printing techniques depends on their compatibility with the printed drug products. This review intent to provide a perspective on the incentives and possible applications of 3D printed pharmaceuticals, besides a practical viewpoint on how 3D printing could be included across the pharmaceutical field.</p> ZAINAB EASSA JASSIM Copyright (c) 2021 zainab jassim 2021-07-07 2021-07-07 77 86 10.22159/ijap.2021v13i4.41741