International Journal of Applied Pharmaceutics

PHARMACOVIGILANCE IN THE ERA OF COVID-19: A CONCISE REVIEW OF THE CURRENT SCENARIO, IMPLICATIONS, AND CHALLENGES

2021-05-13T18:30:47+0530

The pandemic of Coronavirus Disease 2019 (COVID-19) has now affected the entire globe which was first surfaced in China in December 2019. In absence of effective therapy to manage COVID-19, repurposed therapies were being used to manage the condition. In view of an urgent need for definitive therapy, multiple repurposed drugs, and investigational drug candidates are being tried in clinical trials which may lead to the emergence of unknown short term and long term adverse drug reactions (ADRs), and hence it is crucial to assess the safety of the tried therapeutic interventions. The lag in the pharmacovigilance activities in the midst of this pandemic fosters under-reporting of ADRs. Difficulty in causality assessment due to factors like wide variations in clinical presentation, concomitant use of multiple drugs, associated comorbidities, drug-drug and drug-disease interaction which forestalls the appropriate causality assessment. Hydroxychloroquine, a repurposed antimalarial drug has been a part of hue and cry at present because of its in-question safety in patients with cardiac disorders. National and International Drug monitoring centers have stressed upon reporting of ADRs and to boost up the process and come up with various recommendations. We can overcome these issues by working cohesively, motivating HCPs and patients to report ADRs electronically, and by setting up dedicated pharmacovigilance rapid response team to tackle the issues at the earliest.

GASTRORETENTIVE FLOATING TECHNOLOGY FOR ERADICATION OF HELICOBACTER PYLORI: AN INSIGHT VIEW

2021-05-10T10:42:23+0530

Helicobacter pylori is a virulent human pathogen infecting about 50% of the population worldwide. Being a leading cause of gastric ulcer, duodenal ulcer, gastritis, dyspepsia, gastric tumorigenesis etc., this organism has been the focus of concerted study to establish uncertainty of its genetics, immunopathogenesis and cell biology. Scientists have tried to effectively eradicate this pathogen from the gastrointestinal tract in various manners. Inquest of this venture, gastroretentive drug delivery systems including floating dosage forms have emerged as a boon and offer significantly improved therapeutic effects of different antimicrobial drugs. This article presents an evocative review of the structural features, epidemiological evidences and various pharmacotherapeutics vistas. In addition, various novel gastroretentive dosage forms developed so far to combat Helicobacter pylori infection are also discussed. Comprehensive literature review has been performed for this manuscript by utilizing relevant databases like PubMed, SCOPUS, Web of Science, Science Direct, Google Scholar etc., from 1997 up to the year 2020.

FUNDAMENTAL ASPECTS OF A THIRD COMPONENT USED IN TERNARY SOLID DISPERSION: A REVIEW

2021-05-10T13:46:15+0530

Ternary solid dispersion (TSD) is one of the promising approaches used in recent studies to address the issues encountered by poorly water-soluble drugs. The binary solid dispersion (BSD) with the drug and the single polymer is not sufficient to satisfy all the criteria such as improved solubility, dissolution, stability, supersaturation, and recrystallization inhibition. Hence, the TSD with the third component/ternary agent aids in overcoming the limitations, thereby enhancing the solubility and bioavailability to a greater extent when compared to the BSD. Excipients that can be used as a third component includes surfactants, pH modulator, polymer and adsorbents. All these excipients have distinct benefits in improving the efficiency of the final dosage form. However, care must be taken in selecting suitable excipients for the research. This review highlights the impact of these excipients in improving the formulation complications and the therapeutic potential of the TSD.

STATE-OF-THE-ART NANOTECHNOLOGY BASED DRUG DELIVERY STRATEGIES TO COMBAT COVID-19

2021-05-11T12:17:18+0530

The emerging Coronavirus Disease-19 (COVID-19) pandemic has had a global impact on all important aspects of our society. As it is known, SARS-Cov-2 can withstand up to 72 h in adverse environmental conditions, which can aid its rapid spread. Woefully, an efficacious and approbated vaccine for the SARS-CoV-2 virus remains unavailable, which makes the problem more frightening and presently more complicated bestowing forlorn medical care. Nevertheless, global clinical research is studying several over-the-counter (OTC) drugs approved for other indications to confront coronavirus. Over the past decade, therapeutic nanoparticles have been regarded as a felicitous tool for the efficient and persnickety delivery of therapeutic groups (i.e., drugs, vaccines, siRNAs, and peptides) to the site of infection. They can adequately convey the drug encapsulated nanoparticle to a designated locus without instigating unsought effects. Besides, they acquiesce the use of non-invasive imaging methods to monitor the surface of the infection and the response to treatment. The formulated nanoparticle is apposite for intranasal drug delivery which is a meritorious method to deliver therapeutic moiety for viral diseases affecting the lungs. Applying nanoparticles via intranasal route surmounted several demerits of mucosal administration like circumventing enzymatic degradation of the therapeutic moiety, upgrading and prolonging the action of the drug, etc., and can thus corroborate as an exceptional strategy to encounter respiratory viruses like coronavirus. In this article, we illuminate the promising role of nanoparticles as effective carriers of therapeutic or immunomodulatory agents to help combat COVID-19.

The search criteria used were Pubmed, Medscape, Google scholar, etc and the keywords are coronavirus, nanoformulations, nanoparticles, drug delivery, intranasal delivery, etc. The articles range from 2012 to 2020.

A COMPREHENSIVE REVIEW ON PHARMACEUTICAL AND NUTRITIONAL APPLICATIONS OF INULIN

2021-05-10T13:29:26+0530

Inulin is a versatile, water-soluble polysaccharide that is commonly available in nature. In the pharmaceutical industry, the non-digestible function of inulin has made it attractive. Inulin is granted with GRAS status by the FDA and more than 30,000 plants in nature store inulin as a carbohydrate. The chicory is the key plant source of inulin out of all sources. It can be used as the sugar or fat replacer in the processed foods to influence the desirable characteristics. Good biocompatibility, essential chemical properties, and a wide variety of bioactivities have rendered inulin an outstanding natural nutrient. Regulating blood sugar, antioxidant, anticancer is some of the biological activities of inulin. Inulin can also be a carrier for colon/tumor targeting, as only specific enzymes in the colon zhydrolyze the inulin. It allows the growth of micro-flora, the good bacteria in the gut. Inulin is considered as a prebiotic as it is fermented by bacteria that normalize the colon. This review offers an in-depth insight into its novel Pharmaceutical applications as well as sources, processing, physicochemical properties, and nutritional and physiological activities. The chemically modified inulin is gaining a specific interest in the pharmaceutical field with its outstanding properties which are discussed in this review.

NOSE-TO-BRAIN DELIVERY, A ROUTE OF CHOICE FOR TARGETING BRAIN TUMORS

2021-05-10T10:39:44+0530

Brain tumours are the most lethal type of cancer, which is difficult to manage due to the inherent suboptimal bioavailability of the chemotherapy agent at tumour sites, consequent of high levels of protection of physiological blood-brain barrier (BBB), blood tumour barrier (BTB) and blood-cerebrospinal fluid barrier (CSF). Improving the permeability of these barriers would enhance the disease's clinical prognosis and promote patients' quality of life. To this end, scientists have conducted several studies to determine the most suitable route for CNS delivery. Most of which show that the nose-to-brain is proposed to be the most convenient, efficacious and clinically beneficial non-invasive means of delivering chemotherapeutic agents directly to the brain. Therefore, this study compares the therapeutic benefits of intranasal and other conventional brain delivery systems and further evaluates the clinical benefits of using different nanocarriers for brain tumour targeting. However, we surveyed the literature by conducting an in-depth search of the research keywords and their combinations in recognized scientific databases, primarily Science Direct, PubMed, Google Scholar, and Research Gate. Our findings have shown that the nose-to-brain delivery of chemotherapeutics is a breakthrough in bypassing the effects of BBB, BTB, and CSF barriers, improving the delivery of drugs to the brain for specific tumour targeting with desired clinical prognosis.

RISE AND FALL IN SARS-COV-2 GLOBAL PANDEMIC STRAIN RATE–AN OVERVIEW

2021-05-11T13:10:29+0530

After its discovery in Hubei in China in December 2019, the deadly rise of modern coronavirus (COVID-19 or 2019-nCoV) has spread globally. SARS-CoV-2 disease COVID-19 has quickly spread worldwide, posing a serious threat to health and the economy. As of 25th January 2021, more than 100 million confirmed cases of 2,165,581 deaths have been reported by WHO and Worldometer. Many of the cases reported are caused by infection from human to human and are the carriers of this lethal coronavirus. Due to its calamitous nature, the whole world was under lockdown restricting all sorts of movements and means of transportation in hampering the countries economic balance. Presently, the world's endeavor to create and develop a safe and effective COVID-19 vaccine is bearing the fruit. A handful of vaccines now have been authorized around the globe and many more remain in the development phase. In addition, social isolation and knowledge of hygiene (facial masks and sanitizers) are potential methods of controlling the further dissemination of global pandemics COVID-19. This research article presents a brief overview of the catastrophic effect caused by COVID-19 disease globally and particularly in different states of India. Additionally, the article also discusses the recent variant of SARS-CoV-2 and its vulnerable impact. Furthermore, the article investigates the currently available vaccines and those in their development phase for the treatment of COVID-19 disease. This investigatory literature may provide comprehensive details on COVID-19 disease from its inception to grow and later fall in its strain rate.

DEVELOPMENT OF SUSTAINED RELEASE ALOGLIPTIN TABLETS USING A MULTIPARTICULATES SYSTEM MADE OF BENTONITE

2021-05-10T11:29:50+0530

Objective: This study was designed to evaluate the use of bentonite in the formulation of sustained-release tablets containing alogliptin benzoate after granulation.

Methods: Bentonite was used for preparing tablets after granulation. The prepared tablets were tested for their pharmacopeial requirements. Further, a high-performance liquid chromatography (HPLC) method was developed to assess the release pattern of alogliptin from the tablets. Besides, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (XRD) were used for evaluating the compatibility the drugs and bentonite. Finally, the release from the tablets was tested using the paddle apparatus.

Results: The FTIR and DSC did not show any interaction between the drug and the excipient in contrast to the powder-XRD pattern, which showed a shift for montmorillonite crystal peak. This shift was interpreted by increasing in the spacing of the crystalline structure of montmorillonite. However, the results of pharmacopeial tests showed that the prepared tablets comply with the compendial requirements, In addition, the release profiles of these tablets with aid of hydroxypropyl methylcellulose (HPMC) as a binder revealed a sustained release of alogliptin. Furthermore, the fitting of release data showed that the release from these tablets followed Fickian diffusion that alogliptin released by diffusion from bentonite gel matrix.

Conclusion: Bentonite was successfully used for producing sustained-release tablets of alogliptin. However, maintaining the crystal structure of montmorillonite was essential for building the gel structure of bentonite and releasing the drug in a controlled manner.

FORMULATION AND EVALUATION OF AMPHOTERICIN B AND MILTEFOSINE COMBINATION NANOVESICLES

2021-05-22T15:38:08+0530

Objective: The aim of the present investigation is to formulate and evaluate amphotericin B-miltefosine combination nanovesicles for application in the treatment of visceral leishmaniasis.

Methods: Amphotericin B-miltefosine combination (AmB-MTF) nanovesicles were prepared by ethanol injection method. Formulations of nanovesicles were evaluated at varying conditions of lipids composition, drug-lipid proportion, ethanol-water composition and stirring rate, on drug entrapment efficiency and particle size.

Results: The study showed that entrapment efficiency was significantly affected (p<0.01) by the effects of lipids composition, drug-lipid proportion, ethanol-water composition, and stirring rate. Particle size of nanovesicles was significantly affected (p<0.05) by drug-lipid proportion and stirring rate. An optimized formulation of amphotericin B-miltefosine nanovesicles was prepared at optimal factors composition of: phosphatidylcholine-cholesterol-stearic acid 20:4:1, drug-lipid 1:8, AmB-MTF 1:1; ethanol-water 1:4 ratios, and stirring rate 1000 rpm. The AmB-MTF 1:1 nanovesicles formulation showed particle size of 145.6 nm, poly dispersity index 0.19, zeta potential-27.3 mV and drug entrapment efficiency 87%.

Conclusion: Evaluation of AmB-MTF 1:1 nanovesicles showed development of a successful formulation with very good compatibility, extended drug release, convenient vesicle size and high drug entrapment efficiency. To conclude, AmB-MTF 1:1 nanovesicles formulation could be a safe and reliable therapeutic option over the conventional combination therapy provided further antileishmanial investigations are investigated in vitro and in vivo

FORMULATION AND EVALUATION OF IN-SITU GEL CONTAINING LINEZOLID IN THE TREATMENT OF PERIODONTITIS

2021-05-10T18:41:07+0530

Objective: The intent to prepare and evaluate Linezolid in-situ gel in the treatment of periodontitis.

Methods: pH-sensitive in-situ gel was formed by the cold method using a varying concentration of the drug, carbopol 934P and hydroxypropyl methylcellulose (HPMC) and carbopol 934P and sodium carboxy methylcellulose (CMC) (1:1,1:1.5,1:2,1:2.5). An optimized batch was selected based on gelling time and gelling capacity. The prepared in-situ gels were evaluated for appearance, pH, gelling capacity, viscosity, in vitro release studies, rheological studies, and finally, was subjected to drug content estimation and antibacterial activity test.

Results: FTIR study shows drug and physical mixture were compatible with each other. The rheology of formulated in-situ gel exhibited a pseudoplastic flow pattern. this may be because when polymer concentration was increased the prepared formulations become more viscous and in turn delayed the drug release and from the prepared formulation, LF4 and SF4 have polymer concentrations i. e, 0.9% carbopol and sodium CMC showed drug release up to 12 h.

Conclusion: When carbopol is appropriately mixed with other suitable polymers it forms an in-situ gel-forming system that was substantiated by the property to transform into stiff gels when the pH is increased. The in-situ gel was prepared using a combination of carbopol-HPMC and carbopol-Na CMC The formulations LF1 to SF4 showed high linearity (R2 = 0.490-0.682), indicating that the drug was released from the prepared in-situ gel by the diffusion-controlled mechanism. Thus, the formulation of batches LF4 and SF4 containing carbopol: HPMC and carbopol: NaCMC in 1:2 ratios were considered as optimum formulation based on optimum viscosity, gelling capacity and to extend the in vitro drug release.

SYNTHESIS AND CHARACTERIZATION OF STARCH MALONATE: DEVELOPMENT OF FAST DISSOLVING TABLETS OF ACECLOFENAC BY 23 FACTORIAL DESIGNS

2021-05-10T10:02:16+0530

Objective: The aim of the research work is to develop a new superdisintegrant (starch malonate) which can help in enhancing the solubility and drug dissolution of poorly soluble drugs. Hence, starch malonate (new superdisintegrant) was prepared and has been evaluated for its superdisintegrant property by incorporating it into fast dissolving tablets of Aceclofenac.

Methods: Superdisintegrant was developed by using esterification reaction. Prepared starch malonate was then subjected for different characterization tests (solubility, pH, melting point, swelling index, FTIR, DSC studies. 2³ factorial design method was used to formulate fast dissolving tablets of aceclofenac employing starch malonate. Two known superdisintegrants croscarmellose sodium and crospovidone have been used along with starch malonate in combinations to develop fast dissolving tablets. Prepared tablets were then subjected to different tests for tablets like hardness, friability, disintegration time, dissolution studies. A stability study was performed to determine the stability of the formulation. Design expert study was conducted to know the interaction between different superdisintegrants and to select best optimized formulation in among all formulations.

Results: Starch malonate prepared was found to be fine, free flowing slightly crystalline powder, insoluble in aqueous and organic solvents. Tablets of all formulations were of excellent quality concerning drug content (100±5%), hardness (3.8-4.2 kg/cm²), and friability (less than 0.15%). In all formulations, formulation F2 found to be optimized formulation with least disintegration time 38 S, less wetting time 17±0.08 s and enhanced percent dissolved rate in 5 min i.e., 99.84% as compared to other formulations.

Conclusion: From this it was concluded that starch malonate can be used as a novel superdisintegrant to enhance the drug dissolution of poorly soluble drugs. Optimized formulation F2 showed enhanced drug dissolution at 5% concentration as compared to other formulation and showed least disintegration time and enhanced drug dissolution as compared to other formulations and pure drug.

QUALITY BY DESIGN BASED DEVELOPMENT OF ETRAVIRINE SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM

2021-05-10T10:49:08+0530

Objective: The main objective of the present research work was to develop systematically the Self Micro Emulsifying Drug Delivery system of BCS Class IV drug in a Quality by Design framework.

Methods: The quality by design-based formulation development proceeds with defining the Quality Target Product Profile and Critical Quality Attributes of dosage form with appropriate justification for the same. The statistical Mixture design was used for the development of the formulation. The independent variables selected for the design were Oleic acid, Labrasol and PEG 6000, whereas droplet size (nm), emulsification time (sec), % drug loading and % drug release at 15 min were considered as the potential quality attributes of the Self Micro Emulsifying System. The eight different batches of Etravirine-Self Micro Emulsifying systems (ETV-SMEDDS) were prepared and checked for the Critical Quality Attributes. The simultaneous optimization of the formulation was done by the global desirability approach.

Results: The characterization report obtained for all the different batches of formulation was analyzed statistically by fitting into regression models. The statistically significant models determined for droplet size (nm) (R²= 0.96 and p-0.1022), emulsification time (sec) (R²= 0.99 and p-0.0267), % drug loading (R²= 0.93 and p-0.1667) and % drug release at 15 min (R²= 0.96 and p-0.0911) and were statistically significant. The maximal global desirability value obtained was 0.9415 and the value indicates, the selected factors and responses have a good correlation and are significant enough for optimization and prediction of best formulation.

Conclusion: The QbD approach utilized during the development of ETV-SMEEDS facilitated the identification of Critical Material Attributes and their significant impact on the Critical Quality Attributes of SMEDDS. The concept of building quality into product through the QbD application was utilized successfully in the formulation development.

FORMULATION, EVALUATION, AND IN VIVO ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF MORINGA GRANULES

2021-05-10T10:48:16+0530

Objective: Consumption of crude natural products like plants and herbs for mitigation or treatment of illnesses usually accompanied with inconsistent therapeutic effects because of poor solubility and low bioavailability of active phytochemical(s) in addition to product instability. To overcome all of above mentioned drawback ethanol extract of Moringa oleifera leaf was formulated as standardised solid dosage form.

Methods: Different types of materials as an adsorbent, surfactant and other necessary excipients were tested to be use in formulation of Moringa granules utilising wet granulation method. The formulated Moringa granules was then evaluated for organoleptic properties and physical characteristics, in vitro dissolution test, compatibility, drug content, heavy metal tests and microbial limit tests. Additionally, the in vivo anti-inflammatory against Carrageenan-induced paw oedema and anti-arthritic activity against CFA-induced arthritis were also assessed.

Results: 95% ethanol extract of M. oleifera leaves was successfully formulated as standardised granules for oral administration utilising simple and low-cost techniques. Dissolution rate for the marker compounds was increased by an average of 1.076 fold. Animal groups given the prepared Moringa granules showed an improvement in the anti-inflammatory activity and the anti-arthritic activity compared to animal groups given crude extract at the same dose level. Additionally, all the treatment groups showed a significant difference at P<0.05 and P<0.01 compared to control group.

Conclusion: To the best of our knowledge, this work was the first to use gum Arabic in the formulation of a standardised botanical pharmaceutical dosage form of M. oleifera crude extract. Additionally, formulation of Moringa granules apparently improves the drug release profile and bioactivity compare to Crude Moringa extract.

MOLECULAR DOCKING STUDIES OF ISOLATED COMPOUNDS ANDROGRAPHOLIDE AND BETULIN FROM METHANOLIC LEAVES EXTRACT OF ANDROGRAPHIS ECHIOIDES AS ALPHA-AMYLASE AND ALPHA-GLUCOSIDASE ACTIVATORS

2021-05-13T18:34:22+0530

Objective: The purpose of this study is to isolate and characterize the andrographolide and betulin from methanolic leaves extract of Andrographis echioides and also used to evaluate the alpha-amylase and alpha-glucosidase inhibitory activity of isolated compounds using in silico docking studies.

Methods: The isolation was done using column chromatography using gradient mobile phase. Structural elucidation was carried out on the basis of spectral analysis. In this view, andrographolide and betulin were prepared for the docking evaluation. In silico docking studies were carried out using a recent version of Auto Dock 4.2, which has the basic principle of Lamarckian genetic algorithm.

Results: On the basis of the spectral data, the compounds have been established as andrographolide and betulin are being reported from this plant for the first time. The result showed that the andrographolide showed a binding affinity for amylase: (-7.9 kcal/mol) and for glucosidase (-7.2 kcal/mol) while betulin showed (-8.6 kcal/mol) and (-5.2 kcal/mol), respectively.

Conclusion: Therefore, it is suggested that isolated compounds andrographolide and betulin contributed excellent α-amylase and α-glucosidase inhibitory activity because of its structural parameters. Thus, these isolated compounds can be effectively used as drugs for treating diabetes which is predicted on the basis of docking scores.

FLOATING MULTIPLE UNIT MINITABLETS OF METOPROLOL SUCCINATE: FORMULATION, IN VITRO AND IN VIVO CHARACTERIZATION

2021-05-10T21:43:35+0530

Objective: In this present research, formulation of floating multiple unit minitablets of metoprolol succinate without using gas generating agent was attempted with an objective of increased residence time, sustained release, and improved oral bioavailability.

Methods: Solid dispersions were prepared with lipophilic carriers such as compritol ATO888, Gelucire 43/01, Gelucire 39/01, and precirol ATO 05 was formulated using fusion technique. Neusillin US2 was used as an adsorbent. The solid dispersions were compressed into minitablets, weighing 20 mg, and then filled into ‘0’ size capsule.

Results: Formulation F9, F10, F14, and F15 showed instantaneous floating lag time, i.e., 0 min, floating time more than 12 h, and sustained release up to 12 h. Pharmacokinetic study of the optimized formulation (F9) showed 2.46 times increase in area under the curve with increased residence time.

Conclusion: Hence gelucire 43/01 based floating multiple unit minitablets of metoprolol succinate can be considered a promising approach.

A SELECTIVE AND SENSITIVE LC-MS/MS METHOD FOR QUANTIFICATION OF FOUR POTENTIAL GENOTOXIC IMPURITIES IN ATAZANAVIR SULFATE DRUG SUBSTANCE IN TRACE LEVEL

2021-05-10T13:56:57+0530

Objective: The main objective of current research work is to develop and validate a rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the trace analysis of four potential genotoxic impurities in Atazanavir Sulfate drug substance.

Methods: LC-MS/MS analysis of four potential genotoxic impurities was done on Acquity UPLC CSH C₁₈ (100 mm × 2.1 mm, 1.7 μm) column. In this method, mobile phase A (10 mM ammonium acetate) mobile phase B (methanol: acetonitrile (90:10, v/v) with gradient run with the flow rate of 0.2 ml/min. The method was developed with the short run time of 13 min. Triple quadrupole mass detector coupled with positive electrospray ionization was used for the quantification of genotoxic impurities in multiple reaction monitoring (MRM) mode.

Results: The method was linear in the range of 0.3 ppm to 4.5 ppm for BOC Hydrazine Acid impurity, BOC Epoxide and Keto impurity with a correlation coefficient not less than 0.9994. The accuracy of the method was in the range of 99.26% to 105.71% for all four potential genotoxic impurities (PGIs). No impurities were identified in the Atazanavir Sulfate active pharmaceutical ingredient sample.

Conclusion: The proposed method is specific, linear, precise, accurate, robust and stable for the quantification of the four genotoxic impurities at very low levels.

SOLID DISPERSION OF NEBIVOLOL HYDROCHLORIDE IMPREGNATED BUCCAL PATCH: FORMULATION AND CHARACTERIZATION

2021-05-10T12:26:51+0530

Objective: The objective of the present investigation was to design and characterize a mucoadhesive buccal patch of Nebivolol hydrochloride in order to administer a small dose of a drug to treat hypertension effectively and thereby avoiding disadvantages such as patient noncompliance and low bioavailability.

Methods: The buccal patches were prepared by solvent casting method. The polymers used to formulate patches were HPMC K 15 M, PVP K 30, and propylene glycol was used as plasticizer and ethanol as the solvent. The drug-polymer compatibility studied was conducted by FTIR.

Results: All the developed Patches had good transparency and stability. All formulated patches showed pH in the range of 6.49 to 7.22, and drug content was more than 90%. The folding endurance value showed that the patches are flexible and non-brittle. The in vitro residence time was found to more than 30 min. Thickness, % moisture absorption, and % moisture loss values were in a normal range. The drug release study was conducted for 8 h, and it was found drug release was decreased with the increase in polymer concentration. The in vitro release profiles of the drug from all the formulations appeared to follow Korsmeyer Peppa's exponential model, and release exponent (n) was found to be more than 0.45 so that the release can be characterized by Non–Fickian (anomalous) diffusion.

Conclusion: From the results, it was concluded that drug released from formulated buccal patches follows sustained release pattern, Hence can be used for the treatment of the hypertensive patient.

BOOSTING THE SKIN DELIVERY OF CURCUMIN THROUGH STEARIC ACID-ETHYL CELLULOSE BLEND HYBRID NANOCARRIERS-BASED APPROACH FOR MITIGATING PSORIASIS

2021-05-10T11:45:00+0530

Objective: Curcumin presents poor topical bioavailability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of psoriasis. The present study reports the utilization of lipid-polymer hybrid nanoparticles (LPHNPs) for the topical delivery of curcumin which can be a potential approach for mitigating psoriasis.

Methods: Curcumin-loaded LPHNPs were prepared by the emulsification solvent evaporation method and characterized. The optimized Curcumin-loaded LPHNPs (DLN-3) were further incorporated into 2% Carbopol 940 gels and evaluated for its therapeutic efficacy in the Imiquimod (IMQ)-induced psoriasis rat model.

Results: The average particle size, polydispersity index, zeta potential, drug entrapment and loading efficiency for DLN-3 were found to be 200.9 nm, 0.342,-28.3 mV, 87.40±0.99% and 4.57±0.04%, respectively. FT-IR, DSC and XRD studies confirmed that all the components used for the formulation are compatible with each other, whereas SEM and TEM analysis affirmed the spherical shape of LPHNPs with a smooth surface. The in vitro drug release studies suggest that curcumin was released from the LPHNPs in a sustained manner over a period of 24 h via super case II transport mechanism. Results of in vitro skin permeation study revealed that 38.39±2.67% of curcumin permeated at 12 h across excised pig ear skin with a permeation flux of 18.74±3.59 µg/cm²/h. Further, in vivo evaluation and histopathological studies demonstrated that NLHG-1 hydrogels showed better therapeutic efficacy against the psoriatic skin lesions than the standard marketed gels.

Conclusion: These results suggest that the developed LPHNPs have a superior ability to improve the skin penetration or accumulation of DLN-3 within psoriatic skin and offer a potential delivery system for the management of psoriasis.

IN SILICO IDENTIFICATION OF APOBEC3B SMALL MOLECULE INHIBITORS FROM DTP-NCI LIBRARIES

2021-05-10T22:33:57+0530

Objective: APOBEC3B (A3B) enzyme causes C-to-T or C-to-G somatic alteration in the cancer genome, leading to the evolution of a broad spectrum of human cancers. The present study aims to identify A3B small molecule inhibitors using a top-down approach via pharmacoinformatic virtual screening.

Methods: Virtual screening of 2951 drug-alike molecules with diversified structures from the National Cancer Institute Development Therapeutics Program (DTP-NCI) compounds library was performed using GOLD and AutoDock Vina docking programs against the 3D structure of A3B (PDB ID: 5TD5).

Results: Amongst the docked compounds, Nordracorubin, NSC641233 and Raloxifene hydrochloride showed the most potent binding affinities towards A3B on both Autodock/Vina and GOLD. Several significant similarities were observed between A3B and the three hits, including hydrogen bonds and pi-pi stacking. The three compounds also exhibited interaction with the centralized zinc cofactor and amino acid residues that directly contribute the deaminase activity of A3B enzyme.

Conclusion: We hypothesize that the findings from this study could significantly shorten the quest for novel molecules against the A3B after confirmation with subsequent in vitro and in vivo studies in the near future.

RELATIVE COMPARISON OF STABILITY AND DEGRADATION OF METHYLCOBALAMIN TABLETS OF DIFFERENT BRANDS AT DIFFERENT STORAGE SETTINGS

2021-05-10T22:17:32+0530

Objective: To assess relative comparison of stability and degradation of Methylcobalamin tablets of different brands at various storage circumstances.

Methods: The comparative in vitro study of Methycobal (innovator brand) with its other 5 different brands Cobalamin, Neuromet, Incobal, Qbal and Mecobal was organized for evaluation of physicochemical features of hardness, thickness, friability, weight variation, disintegration time and accelerated stability at 3 temperatures, 25 °C, 30 °C±65 % and 40 °C±75 % respectively for 3 mo. Later all brands were passed through HPLC for checking the extent of degradation of drug products.

Results: All tablet brands were within the weight variation specified limits except Mecobal with a relative standard deviation of 6.83%. The weight variation values of Methycobal, Cobalamin, Neuromet, Incobal, Qbal and Mecobal were 0.29%, 0.11%, 0.09%, 0.13%, 0.09% and 0.14% after friability test respectively as per standard limits. The average thickness of Cobalamin, Incobal and Mecobal were not within specified limits. The average hardness of all trades was within limits except Cobalamin and Mecobal exceeding 6kp. The disintegration time of all companies was as per specifications.

Conclusion: Qbal was found economical and cost-effective. However, study facts unveiled no noteworthy variety in the Q. C assessments of Methylcobalamin brands.

ENCAPSULATION OF PARTIALLY PURIFIED BROMELAIN FROM PINEAPPLE CORES IN ALGINATE-PECTIN BEADS AS A TARGETED ANTIPLATELET AGENT

2021-05-10T21:58:33+0530

Objective: Oral administration of bromelain can decrease its bioactivity once it makes contact with stomach acid. Therefore, bromelain was loaded into alginate (Alg), pectin (Pec), and alginate-pectin (AP) beads to control its release into the intestines and avoid degradation.

Methods: Crude bromelain was purified by ammonium sulfate precipitation and the dialysis process. In vitro releases and kinetics studies of bromelain-loaded alginate-pectin beads were carried out using an acid and phosphate buffer medium. The beads were characterized using physical analysis, Fourier-Transform Infrared Spectroscopy (FTIR) analysis, and Differential Scanning Calorimetry (DSC) analysis.

Results: The dialysis fraction of bromelain has a specific activity of 67.93 U/mg, 3.05 times that of crude bromelain. That fraction was encapsulated in Alg, Pec, and AP beads with a range of encapsulation efficiency around 82.70–91.39%. Bromelain-loaded pectin and AP19 beads were chosen to study in an in vitro release based on their swelling properties and encapsulation efficiency. Bromelain-loaded AP19 beads have lower release than bromelain-loaded pectin beads in both dissolution mediums. The cumulative releases of AP19 are 9.99 and 87.81% in 0.1 N HCl and phosphate buffer medium, respectively. Bromelain-loaded P and AP beads both follow the zero-order kinetics model and the dissolution mechanism of the beads is non-Fickian with a combination of diffusion and erosion. The in vitro antiplatelet activity of dissolution aliquots (20.51 and 18.48%) is lower than its dialysis fraction (56.04%).

Conclusion: This in vitro research data shows promising potency for AP as a carrier for oral administration of bromelain as an antiplatelet agent.

DEVELOPMENT, EVALUATION AND RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF QUERCETIN, ELLAGIC ACID AND KAEMPFEROL IN A POLYHERBAL FORMULATION

2021-05-10T21:21:07+0530

Objective: The current study was planned to develop polyherbal tablet formulation, standardization and evaluation for mitigating the symptoms of polycystic ovarian syndrome (PCOS). To control the issue of PCOS in women by the utilization of newly developed polyherbal tablet formulation.

Methods: The polyherbal tablets were prepared using a hydroalcoholic extract of the selected medicinal plants viz. Asparagus racemosus, Bauhinia variegata, Caesalpinia bonducella, Saraca asoca, and Symplocos racemosa with the help of a super disintegrant addition technique using crospovidone, kyron T-314 and pregelatinized starch in various percentages. Evaluation assessments such as pre-formulation studies, weight variation, hardness, friability, thickness, disintegration, IR compatibility and simultaneous estimation of quercetin, ellagic acid and kaempferol by RP-HPLC method were done.

Results: The results reveal that preformulation and evaluation parameters were satisfactory and found to be within an acceptable limit. The Fourier transform infrared spectroscopy (FTIR) compatibility displays no chemical interaction amongst the hydroalcoholic extract of polyherbal formulation and excipients. In simultaneous estimation, the retention time of quercetin, ellagic acid, and kaempferol were found to be 4.86, 6.96 and 10.01 min respectively. The linearity of quercetin, ellagic acid and kaempferol were found in the range of 0-200 µg/ml with correlation coefficients (R²>0.997) within the tested ranges. The LOD and LOQ values of quercetin, ellagic acid and kaempferol were found to be 11.86, 2.63, 5.28 µg/ml and 35.95, 7.98, 16.00 µg/ml respectively. The % RSD values were found to be less than 2 showed the optimized method is precise.

Conclusion: To conclude, the prepared polyherbal tablet and its quality control analysis revealed satisfactory pharmaceutical properties that fulfill within the limits of pharmacopeial standards. The RP-HPLC method for simultaneous estimation of quercetin, ellagic acid and kaempferol were simple, precise, accurate and consistent for the quantitative analysis and quality control examination of herbal formulations.

ENHANCEMENT OF THE SOLUBILITY OF FAMOTIDINE SOLID DISPERSION USING NATURAL POLYMER BY SOLVENT EVAPORATION

2021-05-10T14:34:44+0530

Objective: The aims of the study to enhance solubility and dissolution of famotidine using natural polymer. Solubility study of a drug is one of the contributing factors of its oral bioavailability. The formulation of poorly soluble drugs for oral delivery presents a challenge to the formulation technologists.

Methods: The present study has shown that it is possible to raise the solubility for poorly soluble drugs like famotidine, by preparing solid dispersion using natural water-soluble polymer (xyloglucan and hyaluronic acid) as solubilizer through solvent evaporation method. Physical mixture and solid dispersion of famotidine with xyloglucan (XG) or hyaluronic acid in a ratio of 1:1, 1:2, 1:3 were prepared. Solubility study, drug content, dissolution profile and compatibility study were performed for famotidine in solid dispersions XS1, XS2, XS3, HS4, HS5, HS6 as well as in physical mixtures at a ratio 1:1 for both polymer (XG and hyaluronic acid).

Results: It was observed that solid dispersions of each drugs showed an increase in dissolution rate in comparison with its pure drug in the ratio of 1:1 (Drug: carrier). It can be concluded that with the care and proper use of xyloglucan, the solubility of drugs poorly soluble can be improved.

The prepared solid dispersion showed improvement of drug solubility in all prepared formulas. The best result was obtained with formula XS1 (famotidine: xyloglucan at ratio 1:1) that showed 26 fold increase in solubility compared to the solubility of pure drug.

Conclusion: The natural solid dispersion, increased wettability and reduced crystallinity of the drug which leads to improving solubility and dissolution.

DEVELOPMENT AND STATISTICAL OPTIMIZATION OF GASTRORETANTIVE FLOATING MICROSPHERES OF PREGABALIN PREPARED BY W/O/O MULTIPLE EMULSION METHOD

2021-05-10T20:04:33+0530

Objective: The aim of this study is to develop a gastroretentive microsphere of pregabalin using design of experiment (DoE) to decrease dosing frequency and increasing bioavailability.

Methods: Pregabalin microsphere was prepared by W/O/O multiple emulsion method using a mixture of ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) as rate-controlling polymer. Mixed solvent system comprising of dichloromethane (DCM) and acetonitrile (ACN) and light liquid paraffin was chosen as primary and secondary oil phase respectively. Taguchi design was employed for factor screening and Box Behnken design was used for the optimisation of critical process parameters.

Results: Taguchi design revealed that polymer: drug, DCM: ACN and PVP: EC is the critical factor for the preparation of microspheres. The optimized formulation was prepared using polymer: drug (4.95:1), DCM: ACN (53.76: 46.24) and PVP: EC (2:5) which showed mean particle size of 203.34±4.82 µm, practical yield of 87.52±2.91 %, encapsulation efficiency of 96.43±3.14 %, floating ability up to 90.42±1.64 % and T60% of 332.81±5.84. Drug release from microsphere followed Higuchi Kinetic model.

Conclusion: In a nutshell, microspheres with excellent flowability and great encapsulation efficiency were successfully developed. These can be useful in improving patient compliance by reducing frequent dosing.

VALIDATED STABILITY INDICATING HPLC APPROACH FOR QUANTIFYING TRICHOLINE CITRATE AND CYPROHEPTADINE SIMULTANEOUSLY IN SYRUP FORMS

2021-05-10T13:41:45+0530

Objective: This investigation demonstrates a stability-indicating and reliable “high-performance liquid chromatography” method to simultaneously quantify tricholine citrate (TEC) and cyproheptadine (CRH) in the syrup form and bulk form.

Methods: Successful separation was accomplished using C18 “Agilent column (250 mm × 4.6 mm, 5 μm)” with isocratic type of elution using mobile phase containing 0.1 M NaH₂PO₄ buffer and acetonitrile at 55% volume and 45% volume ratio, respectively with 1.0 ml/min flow rate. The wavelength sensor was attuned at 263 nm to quantify TEC and CRH.

Results: TEC and CRH peaks were eluted with fine resolution at retention times 1.837 min and 2.936 min, respectively. In the 137.5-412.5 μg/ml and 1-3 μg/ml concentration ranges for TEC and CRH, the calibration graphs were linear, with regression coefficients of 0.9999 and 0.9998, respectively. The suggested "high-performance liquid chromatography" approach has been shown as sensitive, precise, robust, accurate, specific and stability indicating through the resolution of TEC and CRH from its degradation-based compounds.

Conclusion: The established high-performance liquid chromatography technique was effectively extended to the evaluation of TEC and CRH in the combined syrup form and the test results appeared satisfactory.

FORMULATION AND OPTIMIZATION OF NATURAL GUM BASED EXTENDED RELEASE TABLETS OF LOSARTAN USING D-OPTIMAL MIXTURE DESIGN

2021-05-11T11:54:35+0530

Objective: Losartan potassium is one of the widely prescribed antihypertensive drugs administered orally and its extended-release tablet formulations are essentially required for the long-acting effect at reduced dosage frequency. The present research was aimed for the development and optimization of an extended-release tablet of losartan potassium, exploring natural gums, i.e., xanthan gum and guar gum as drug release modifiers.

Methods: The tablet formulation was prepared by wet granulation method and the formulation optimization was done by D-optimal mixture design using Design Expert^® software. The independent variables studied were xanthan gum (X₁), guar gum (X₂) and lactose (X₃) taking various combinations of the total amount of gum and ratio of xanthan gum to guar gum under the given constraint range. The dependent (response) variables studied were % drug release in 1h (Y₁), 4h (Y₂), 7h (Y₃) and 10h (Y₄). The developed tablets were evaluated for physical properties, i.e., hardness, friability, weight variation as well as the in vitro drug release profiles. For optimization studies, the polynomial equations and response surface plots were generated and the optimized formulation was selected on the basis of maximum desirability value.

Results: The developed tablet formulation was found to possess all physical properties within the desired range and showed sustained release profile with ~80% drug release in 10 h duration. The model fitting studies demonstrated best fit in the zero-order model and the slope value of Korsmeyer–Peppas plot was ˃0.89, suggesting case II transport as a drug release mechanism.

Conclusion: The findings suggested that natural gums-based matrix tablets of losartan could be successfully developed and natural gums can be explored as platform technology as release retardants and in the development of sustained-release matrix tablets of other drugs.

A 23 FACTORIAL DESIGN FOR FORMULATION AND DEVELOPMENT OF DOXYCYCLINE HYDROCHLORIDE IN SITU GEL FORMING SOLUTION FOR WOUND HEALING APPLICATION

2021-05-10T08:46:21+0530

Objective: To develop and formulate doxycycline hydrochloride hydrogels employing various polymers for wound healing application.

Methods: A thermo-reversible gel can transmute from a sol-gel in replication to environmental temperature vicissitudes made up of gallic acid (GA) and tamarind seed polysaccharide (TSP). An antimicrobial agent (doxycycline hydrochloride) integrated to provide the benefit and efficiently safeguard the wound from infection. A low temperature causes TSP to aggregate intermolecularly with GA to create a gel network. GA–TSP gel heat stability increased with increased concentration of GA. Prepared gel formulations were optimized by 2³ factorial designs further evaluated for stability and compatibility, appearance, gelation temperature, gravitational flow simulation, in vitro release, in vivo excision wound model in rats.

Results: A strong viscoelastic gel was formed at body temperature in the GA–TSP mixture containing 0.6% (w/v) GA. The prepared formulation exhibited absolute stability and compatibility. The formulations indicated a range of 23±1.47 to 50±1.40 °C. The viscosity values were in the range 6628 to 19146 cps. The optimized gel formulation (DT8) was prepared to analyze the checkpoints and further evaluated for gelation temperature ( °C), viscosity (cps), gelation time (s), and in vitro release of drugs (percent cumulative release of drugs) up to 12 h reflecting R1=36.5±0.61 °C, R2=12887±11 cps, R3=16.2±1.38 min and R4=94.65±0.59 percent. Formulation DT8 showed significant wound healing property and it is comparable to the control group. Formulation DT9 treated group showed faster epithelialization and greater rates of wound contraction in rats.

Conclusion: The formulations comprising of TSP with antimicrobial agents demonstrated to be efficient in wound healing. Out of all formulations, DT8 showed better wound healing ability, which is evident from in vivo studies.

FABRICATION OF MICROEMULSION LOADED SUBLINGUAL FILM FOR RAPID ABSORPTION OF FENTANYL CITRATE IN TRANSIENT BREAKTHROUGH PAIN

2021-05-10T12:16:20+0530

Objective: The present research work aims to develop a microemulsion loaded sublingual film for rapid absorption of fentanyl citrate in transient breakthrough pain.

Methods: The Fentanyl citrate microemulsion loaded sublingual film was prepared using Capmul MCM C8 (oil), tween 20 (surfactant) and propylene glycol (co-surfactant) with different grades of film-forming polymer (HPMC) using a film casting machine. The films were evaluated for in vitro disintegration study, tensile strength, folding endurance, content uniformity, drug content, in vitro dissolution, pH, thickness and weight variation, scanning electron microscopy, ex vivo permeation study, droplet size, polydispersity index, zeta potential, % moisture content and stability study were evaluated.

Results: The optimized film formulation showed desired mechanical properties (tensile strength of 0.291 kg/cm²) and a minimum disintegration time of 20 s. The optimized sublingual film formulation exhibited 43.16 % of FC microemulsion loading. Morphological study showed the absence of drug crystals on the polymeric surface. Permeation studies through goat sublingual mucosa indicated 89% fentanyl citrate release through fentanyl citrate microemulsion loaded sublingual film, whereas only 40% fentanyl citrate release was obtained when it was directly added to film without microemulsion strategy.

Conclusion: The present study indicated that extend of permeation of fentanyl citrate when added to the sublingual film in microemulsion form was around 2.225 folds higher than when added directly to film without microemulsion. The present microemulsion embedded film technology could be a promising alternative to conventional drug delivery systems and traditional routes of administration for breakthrough pain management.

VIRTUAL TARGET CONSTRUCTION FOR STRUCTURE-BASED SCREENING IN THE DISCOVERY OF HISTAMINE H2 RECEPTOR LIGANDS

2021-05-10T22:11:46+0530

Objective: This study aimed to develop validated targets to be employed in structure-based virtual screening (SBVS) to discover ligands for the human histamine H₂ receptor (hHRH2).

Methods: The virtual targets construction was initiated by homology modeling with the reference compound ranitidine as the ligand followed by 100 ns molecular dynamics (MD) simulations. During MD simulations, the snapshot with the lowest value of the free energy of binding was selected for further validation by re-docking simulations. All simulations were performed in YASARA-Structure.

Results: The research presented here resulted in one validated target for the SBVS. Additionally, by employing a clustering module in MD simulations analysis in YASARA-Structure, more than ten different virtual targets are also available for further uses.

Conclusion: The virtual targets resulted in this research offer possibilities to construct valid SBVS protocols to identify ligands for the hHRH2.

RAPID AND SIMPLE DETERMINATION OF IBUPROFEN AND CAFFEINE IN FIXED-DOSE COMBINATION FORMULATIONS: APPLICATION TO DISSOLUTION STUDIES

2021-05-10T15:28:13+0530

Objective: To develop a UV-derivative spectrophotometric method with zero-crossing determinations for the simultaneous quantification of ibuprofen (IBU) and caffeine (CAF) in fixed-dose combination formulations (soft gelatin capsules). The proposed method was validated, and it was applied to determine the in vitro dissolution performance of IBU and CAF from a commercial formulation.

Methods: The method is based on the use of the second-derivatives of the zero-order spectra and measurement at zero-crossing wavelengths. Linearity, accuracy, precision, stability, and influence of the filter were evaluated. Dissolution profiles of IBU and CAF were obtained with the USP Apparatus 2 at 100 rpm and 900 ml of 0.1 M phosphate buffer pH 7.4 as dissolution medium. Dissolution samples were treated with the proposed UV-derivative method and results were compared with data previously published.

Results: The zero-crossing points for the determination of IBU and CAF were found at 235.6 nm and 218.8 nm, respectively. The method was linear in the range of 7.5-15 µg/ml for IBU and 5-25 µg/ml for CAF (R²>0.999, *P<0.05). The precision and accuracy of the method were within acceptable criteria (CV<0.99% and recovery 97.97% for IBU and CV<1.76% and recovery 99.05% for CAF). Fiberglass filters were the best option to filter samples and stability of all drugs was adequate when solutions were stored at 25 °C during 24 h. Dissolution of IBU and CAF at 60 min was 99-100% with dissolution profiles of sigmoidal S-shape. Weibull function and Logistic were the best-fit models that describe the in vitro dissolution performance of both drugs.

Conclusion: The proposed UV-derivative method allows the simultaneous determination of IBU and CAF in fixed-dose combination formulations. The method generates reliable information that can be compared with published data. The proposed UV-derivative method is rapid and simple and can be easily adopted for routine analysis of IBU and CAF.