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 THE RESEARCH UPDATES AND PROSPECTS OF HERBAL HARD-BOILED LOZENGES: A CLASSICAL PLATFORM WITH PROMISING DRUG DELIVERY POTENTIAL <p>Over the past decades major focus has been given towards innovative drug delivery systems and new dosage forms. This is due to highly expensive process and high attrition rates of existing marketed drugs. Hard-boiled lozenges (HBLs) are one of the solid dosage form designed to release the drug in saliva for either local or systemic effects. Typical application of lozenegs includes throat infection, pharyngitis, cough suppressant, nasal-decongestant, expectorants, and smoking cessation. The drug delivery through the hard-boiled candies has an easy marketing advantage due to its attractive appearance and patient compliance. As a part of the drug is absosrbed into systemic circulation, gastrointestinal degradation and fast pass effects are avoided. Further, drug delivery through hard-boiled lozenges can be potential platform for some of the suitable drug candidates. This review on hard-boiled lozenges discusses manufacturing process, characterization techniques, quality control, research studies and market potential of hard-boiled lozenges. The major databases searched were, PubMed, Wiley Online, Medline, Elsevier, Google scholar, Scopus, ACS, The Royal Society of Chemistry, SciFinder, Baidu Scholars, CNKI, web of science, Cochrane database, US Patents, Espacenet and various business reviews. This review provides comprehensive information on hard-boiled lozenges that will help the pharmaceutical scientist from academia as well pharmaceutical industry to leverage the potential of this conventional dosage form for various herbal drugs and other pharmaceutical actives.</p> MANAS RANJAN SAHOO MARAKANAM SRINIVASAN UMASHANKAR RAMESH RAGHAVA VARIER Copyright (c) 2021 Manas Ranjan Sahoo, Umashankara Marakanam Srinivasan, Dr. Ramesh Raghava varrier 2021-03-07 2021-03-07 1 13 10.22159/ijap.2021v13i2.40165 AN OVERVIEW OF TECHNOLOGY TRANSFER AS A REGULATORY ASPECT <p>Technology Transfer is fundamental and crucial to the drug development process for new drug products. The great decision is based on that factor in which the concept or process is advanced from research and development-oriented scheme to aimed towards the commercialization of the drug. The transfer could also be said to achieve success if the receiving section and the transferee can efficiently use the technology for profit. The achievement relies upon an understanding of the process or the capability to predict exactly the future prospects of a process. The main intention of this review article is to study the Regulatory aspects of technology transfer. This review article is mainly focused on the Consequence of technology transfer, the purpose for technology transfer in industries, barriers concerned with technology transfer, classification regarding technology transfer, facets of technology transfer, and steps among technology transferThis review was carried out by systematic searches of data integrity in relevant ICH, WHO, and US guidelines, published articles, reviews and abstracts in Google scholar, Pubmed, Science direct, Embase, Web of science of articles up to 2020.</p> G. M. PAVITHRA MANORANJITH S. NAGALAKSHMI Copyright (c) 2021 Dr.S. Nagalakshmi, G.M.pavithra 2021-03-07 2021-03-07 14 19 10.22159/ijap.2021v13i2.40067 ISOTRETINOIN FOR TREATING ACNE VULGARIS <p>Acne vulgaris (AV) occurs in more than 80% of dermatological cases in adolescents and young adults and affects the quality of life. Oral isotretinoin, a metabolite product of vitamin A, is well-known to be the most effective treatment for severe nodulocystic AV and moderate AV that does not respond to other therapeutic modalities. Thus, this literature review was conducted to explain the mechanism of action, effectiveness, contraindications, side effects, and safety of oral isotretinoin in AV, which provided essential information for dermatologists. Furthermore, isotretinoin is the only treatment modality that has implications for the entire pathogenesis of acne. It contributes to decreasing corneocytes’ adhesion, supporting cellular proliferation and follicular renewal, induction of cell apoptosis, and immune regulation. The effectiveness of AV therapy with isotretinoin has expanded as it is also indicated for moderate to severe AV that does not respond well to topical combination therapy or systemic antibiotics. However, isotretinoin is included in Category X drugs and may induce many side effects from mucocutaneous effects to teratogenicity. From this extensive literature review, it can be concluded that isotretinoin is one of the treatment modalities for acne with good effectivity due to its mechanism of actions that affect the entire acne pathogenesis. Considering the various side effects of isotretinoin, its use requires adequate clinical assessment and monitoring by a dermatologist.</p> IRMA BERNADETTE S. SITOHANG Copyright (c) 2021 Irma Sitohang 2021-03-07 2021-03-07 20 25 10.22159/ijap.2021v13i2.40045 TREATMENT POSSIBILITIES FOR ACQUIRED AND HEREDITARY DISEASES BY GENE THERAPY: A REVIEW <p>Therapeutic nucleic acids demand specificity and accuracy in design as well as delivery strategies used in replacement or silencing of the target gene. Gene therapy is believed to be the therapy in which the root cause of the diseases can be treated at the molecular level. Generally gene therapy helps in the identification of the origin of the disorder instead of using drugs to diminish or control the symptoms. The application of nucleic acids to treat and control diseases is known as “gene therapy.” Gene therapy consists on the substitution or addition of a functional gene into the nucleus of a living cell, in order to treat a disease or repair a dysfunction, caused by this gene failure. This therapy is used to correct defective genes, which are responsible for genetic diseases. Thus, gene therapy can be used to prevent, treat or regulate hereditary or acquired disorders, by the production of therapeutic proteins. The gene therapy is mediated by the use of viral and non-viral vectors to transport foreign genes into somatic cells to restorative defective genes. This review focuses on viral vectors in detail.</p> P. V. KAMALA KUMARI G. EKSHITHA, V. HARIKA Copyright (c) 2021 Kamala Kumari Paravastu 2021-03-07 2021-03-07 26 32 10.22159/ijap.2021v13i2.39995 SAMPLE PREPARATION AND BIOANALYSIS VALIDATION FOR NATURAL PRODUCT SAMPLE <p>Bioanalysis study and its validation are important for the application in natural drug discovery and preparation for natural medicine products with safe drug development approaches. Bioanalysis data for natural products can provide quantitative information on active compounds from natural products for pharmacokinetics, pharmacodynamics, bioavailability, bioequivalence, and toxicokinetics. Bioanalysis validation provides useful guidance for obtaining accurate data on drug discovery, preclinical and clinical testing of natural drug product development, and to ensure the methods used are suitable for application in testing the samples. In general, sample preparation and validation of the bioanalysis method are part of the pharmacokinetic characterization of a chemical compound from the discovery to the development stage of natural material products. Therefore, this paper aims to discuss how to prepare samples and validate bioanalysis for natural products.</p> IDA AYUMIATI FEBRINA AMELIA SAPUTRI MUCHTARIDI MUCHTARIDI Copyright (c) 2021 Ida Ayumiati 2021-03-07 2021-03-07 33 47 10.22159/ijap.2021v13i2.39034 TREATMENT MODALITIES OF THE COVID-19 PANDEMIC THROUGH REPURPOSED DRUGS AND STATUS OF VACCINES <p>Respiratory diseases are&nbsp;the leading source of morbidity and death&nbsp;for millions around the world of all ages. A 2019 coronavirus&nbsp;outbreak has occurred in China&nbsp;and is spread quickly throughout nearly all&nbsp;across the world. To introduce prevention measures that have contributed to a sudden upturn in the rate of cases around the globe, several nations responded too late. It has prompted nations to close the borders, halted companies, kept&nbsp;people inside their homes, and numerous other measures to prevent their spread.</p> <p>We systematically searched on Google scholar, PubMed, LitCovid, and MedRxiv using the search terms coronavirus, severe acute respiratory syndrome, 2019-nCoV, SARS-CoV-2, SARS-CoV, MERS-CoV, COVID-19, and vaccine for published articles. Present or performed clinical studies were found on the ClinicalTrials. gov, the Chinese Clinical Trial Registry, and the International Clinical Trial Registry site using the disease searches phrase coronavirus infection.</p> <p>Many repurposed drugs, including antivirals, antibiotics, monoclonal antibodies, corticosteroids, and others, were found to be effective against the novel COVID-19. Governments, private firms, researchers, and non-profit organizations are working hard to create a COVID-19 vaccine.</p> <p>In addition to the new medicines and old drug clinical testing, SARS-CoV-2 vaccines must also be designed and developed. Moreover, positive news in the development of vaccines suggests that new vaccines will be available on the market soon and a bowl of immunity against this virus can be established, thus limiting the spread and eradication of this deadly virus from the surface of the world as with so many viruses.</p> MD SADIQUE HUSSSAIN MOHIT PARUL PAMMA BABY KUMARI Copyright (c) 2021 Md Sadique Hussain 2021-03-07 2021-03-07 48 58 10.22159/ijap.2021v13i2.40554 WILL THE TRADITIONAL MEDICINE UN-PAUSE THE WORLD AND DECIDE THE FATE OF COVID-19? <p>COVID-19 is a life-threatening disease that mainly affects the human respiratory system. In today’s world, scientists are working conscientiously for the identification of promising drugs and vaccines. But, when we look back to the former times, herbal medicines were considered for curing most of the diseases; luckily, nowadays, natural remedies are being carried forward by few researchers even for the treatment of most life-threatening diseases like cancer, diabetes and alzheimer’s etc. So, why can't we attempt the herbal formulation for the management of COVID-19 too? Since there is no proper scientific validation for traditional herbs and spices; it just can’t be simply ignored. When a product with less or few side effects can be prepared and made available for the benefit of people, there is nothing wrong in pondering them. Thus, keeping these points in mind, in this article, we have discussed about SARS CoV-2, their treatment options and the impact of natural remedies on both the former as well as novel coronavirus. Further, we have also emphasized on traditional Chinese medicine, various flavonoids and kabasura kudineer and their impact on coronavirus infection. Till now, there is no particular drug or vaccine available for the treatment of COVID-19; thus prevention is the only option. But, we hope that thorough study; screening, preclinical and clinical evaluation of natural compounds may give some action against SARS CoV-2. Moreover, incorporating natural herbs and spices in our diet can help in boosting immunity and fight against various life-threatening diseases.</p> JANANI S. K. DHANABAL S. P. SURESHKUMAR R. CHENMALA KARTHIKA SAI SURYA NIKITHA UPADHYAYULA Copyright (c) 2021 Janani S.K., Dr. Dhanabal S.P, Dr. Raman Sureshkumar, Sai Surya Nikitha Upadhyayula, Karthika Chenmala 2021-03-07 2021-03-07 59 66 10.22159/ijap.2021v13i2.40413 NOSE-TO-BRAIN DRUG DELIVERY: AN UPDATE TO THE ALTERNATIVE PATH TO SUCCESSFUL TARGETED ANTI-MIGRAINE DRUGS <p>The Blood-Brain Barrier (BBB) limits transportation to the brain of possible treatment moieties. Specific stimulation of the brain through olfactory and trigeminal neural pathways by BBB has been taken into consideration for the development of a wide spectrum of brain therapeutics. The intranasal delivery path delivers the drugs through the brain, eliminating any side effects and increasing neurotherapeutics performance. Diverse drug delivery systems (DDDss) for reaching the brain via the nasal route have been researched over the past few decades. Large-scale molecular biologics, such as Deoxyribonucleic acid (DNA), gene vectors, and stem cells, can be administered intranasally, as a method for the management of a range of CNS illnesses, including stroke, Parkinson's diseases, multiple sclerosis, Migraine, Alzheimer's diseases, epilepsy, and mental disorders. New DDSs, including nanoparticles, liposomes, and polymeric micelles, have acquired potentials in the nasal mucosa and central nervous system (CNS), as effective means of concentrating the brain without toxicity. Differential nasal cavity structures posed a significant obstacle in ineffective drugs beyond the nasal valve. Pharmaceutical firms have increasingly used emerging techniques for the production of new nasal pharmaceutical drugs to overcome these obstacles. This review aims to identify the new advances in the nasal administration of brain-based DDSs for Migraines.</p> SOUVIK CHATTOPADHYAY SUJIT DAS KOUSHIK NARAYAN SARMA Copyright (c) 2021 Souvik Chattopadhyay, Sujit Das, Koushik Narayan Sarka 2021-03-07 2021-03-07 67 75 10.22159/ijap.2021v13i2.40404 UFASOMES: UNSATURATED FATTY ACID BASED VESICULAR DRUG DELIVERY SYSTEM <p>Various novel drug delivery systems have been developed encompassing several administration routes to deliver drugs at a rate decided as per the need of the body during the course of treatment and to achieve targeted therapy, also decreases undesirable side effects. Different types of vesicular drug delivery systems were developed, such as liposomes, niosomes, ufasomes etc. Ufasomes are unsaturated fatty acid vesicles which is a suspension of closed lipid bilayer formed from fatty acid and their ionized species having limited, narrow pH ranging from 7-9. Composition of fatty acid molecules is such that the hydrocarbon tails are pointed towards the inner core of the membrane and the carboxyl group are in touch with water. Stable ufasomes preparation mainly relies on appropriate choice of fatty acid, cholesterol quantity, range of the pH, buffer and lipoxygenase amount. Recent innovation provides very efficient features such as stability considerations, dynamic features and microscopic features of ufasomes. The article furthermore provides the difference between ufasomes with liposomes. For this review, the complete databases have been collected from various search engines such as researchgate, elsevier, pubmed, sciencedirect, google scholar, scopus etc., from the year 1965-2020 using the following keywords.</p> ARUNDHASREE RAJALAKSHMI R. AISWARYA R. ABHIRAMI RAJENDRA KUMAR SREELAKSHMI S. KUMAR SREEJA C. NAIR Copyright (c) 2021 sreeja c nair, arundhasree, rajalakshmi r, aiswarya r, abhirami rajendra kumar, sreelakshmi s kumar 2021-03-07 2021-03-07 76 83 10.22159/ijap.2021v13i2.39526 BINGE EATING DISORDERS; UPDATED AND EMERGING APPROACHES <p><strong>Objective: </strong>Binge eating disorders (BED) recently become a global health care issue for clinicians with detrimental effects on all organ systems. A multidisciplinary strategy including pharmacotherapy is required for its management.</p> <p><strong>Methods: </strong>This review is intended to comparatively evaluate the relative efficacy of different pharmacological agents in BED treatment with new therapeutic approaches, focusing on the clinical evidence and on Phase III randomized controlled trials.</p> <p><strong>Results: </strong>Data suggest that certain treatments have advantages over placebos to reduce binge eating features; however, the small duration of such research with the lack of adequately sized trials was the major limitation in interpreting these findings. Furthermore, these medications are mostly not greatly efficient for BED associated with obesity except for topiramate, which markedly improves the features of binge episodes with weight loss. Till now, lisdexamfetamine is still the only drug with regulatory permission for BED therapy; however, its weight loss efficacy has not been established.</p> <p><strong>Conclusion: </strong>Drugs alone or in combination approaches may be useful pharmacotherapies to yield promising outcomes acutely and over longer-term follow-up in the treatment of BED.</p> MAHMOUD TEAIMA MAGDI M. ABDEL HAMID NABIL A. SHOMAN BHASKARA R. JASTI MOHAMED A. EL-NABARAWI MOHAMED YASSER Copyright (c) 2021 mahmoud teaima, Magdi Abdel Hamid, Nabil Shoman, Bhaskara Jasti, Mohamed El-Nabarawi, Mohamed Yasser 2021-03-07 2021-03-07 84 93 10.22159/ijap.2021v13i2.40214 NIOSOMES AS AN APPROACH TO IMPROVE THE SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS II DRUGS <p>Based on their solubility and permeability, drugs are typically divided into four classes (Classes I–IV) according to the biopharmaceutics classification system (BCS). Of these classes, BCS class II drugs have high permeability and low solubility; not only do these characteristics constitute the rate-limiting step in the formulation of these drugs but the low solubility in water results in low bioavailability. Thus, methods for improving their solubility have been developed using lipid carriers such as liposomes, niosomes, and aquasomes; other approaches include self-micro-emulsifying drug delivery systems (SMEDDS) and self-nano-emulsifying drug delivery systems (SNEDDS). Currently, niosome-based drug delivery systems that utilize nonionic surfactants, drugs, and cholesterol in varying ratios are being widely used to deliver both hydrophilic and lipophilic drugs in addition to several other applications of niosomes.</p> GAURANG SAWANT GEETA BHAGWAT Copyright (c) 2021 Gaurang Sawant, Geeta Bhagwat 2021-03-07 2021-03-07 94 101 10.22159/ijap.2021v13i2.40423 THERMOSENSITIVE HYDROGELS–A POTENTIAL CARRIER FOR THE DELIVERY OF DRUGS AND MACROMOLECULES <p>In this review, the authors have discussed scientific advances in thermosensitive hydrogels over the past two decades. The ability of the thermo-sensitive hydrogel to undergo rapid changes with response to temperature makes it an attractive candidate for many biomedical applications such as targeted drug delivery, wound healing, soft contact lenses, sensors, tissue regeneration, gene, and protein delivery. This review aims to deliver a brief overview of gelation properties, merits, and demerits of various natural and synthetic thermo-sensitive polymers that have significant clinical relevance. The report emphasizes the importance of injectable thermosensitive hydrogels, as it can offer improved solubility of hydrophobic drugs and site-specificity, extended-release of drugs and macromolecules, improved safety, and local administration of drugs. The authors has also provided a commentary on the delivery of drugs or macromolecules from thermo-sensitive hydrogels through various approaches. This review highlights the current status of research in thermo-sensitive hydrogels and emphasizes the importance of developing nontoxic thermo-sensitive hydrogels, dual responsive, and multi-responsive hydrogel systems.</p> SOUMYA RANJANA SAHOO MOTHILAL M. PRIYADHARSHINI B. DAMODHARAN N. Copyright (c) 2021 Mothilal M, SOUMYA RANJANA SAHOO, PRIYADHARSHINI B 2021-03-07 2021-03-07 102 109 10.22159/ijap.2021v13i2.40162 BIOANALYTICAL METHOD VALIDATION FOR DETERMINATION OF ROSMARINIC ACID IN SIMULATED BIOLOGICAL MEDIA USING HPLC <p><strong>Objective: </strong>This study aims to develop and validate a simple, rapid and accurate HPLC method for the determination of rosmarinic acid (RA), an active marker of <em>Thunbergia laurifolia</em> (TL) tea, in Hank's Balanced Salt Solution (HBSS) using HPLC.</p> <p><strong>Methods: </strong>The separation was performed using a Xterra<sup>®</sup> C<sub>18</sub> reversed-phase column (150 &nbsp;3.9 mm, 5 µm). The mobile phase consisted of 0.5% (v/v) glacial acetic acid (A) and acetonitrile (B). The flow rate was 1 ml/min and detection was carried out at 330 nm with UV-visible spectrophotometer. The method was validated according to the US FDA guidance on bioanalytical method validation in 2018.</p> <p><strong>Results: </strong>The method was successfully validated in the range of 50-500 ng/ml of RA. Intra-and inter-day precision ranged from 1.6 to 2.1% and 1.4 to 4.5%, respectively. Intra-and inter-day relative errors (% bias) were less than 7.6 and 3.6%, respectively. In addition, it was found that the stability of RA in HBSS could be dependent on the pH and temperature.</p> <p><strong>Conclusion: </strong>The developed method met the validation requirements and could be further applied to the permeability study of RA using an <em>in vitro</em> Caco-2 cell monolayer model.</p> KOTCHAPHAN CHOOLUCK PIYANUCH ROJSANGA CHUTIMA PHECHKRAJANG MONTREE JATURANPINYO Copyright (c) 2021 Kotchaphan Chooluck, Piyanuch Rojsanga 2021-03-07 2021-03-07 110 113 10.22159/ijap.2021v13i2.40372 EMULSOMES FOR LIPOPHILIC ANTICANCER DRUG DELIVERY: DEVELOPMENT, OPTIMIZATION AND IN VITRO DRUG RELEASE KINETIC STUDY <p><strong>Objective: </strong>The objective of the present study was to formulate and characterize paclitaxel (Ptx) loaded sterically stabilized emulsomes to provide non-toxic and biocompatible carriers with high Ptx loading efficiency.</p> <p><strong>Methods: </strong>Plain (P-Es) and sterically stabilized emulsomes (SS-Es) were prepared by a modified solvent evaporation method using tristearin as solid lipid and optimized for lipid to (DSPC+CHOL+DSPE-PEG)/ tristearin ratio, lipid/lipid-PEG (DSPC+CHOL/DSPE-PEG) molar ratio, solid lipid concentration, phospholipid concentration, organic to aqueous phase volume and homogenization time based on their effect particle size and entrapment efficiency. Optimized emulsomes were characterized for morphological features, <em>in vitro</em> drug release kinetics and protection from plasma protein.</p> <p><strong>Results: </strong>The emulsomes so formed were uniform in size with a mean particle diameter of 275±5.52 and 195±6.4 nm for P-Es and SS-Es respectively. All the formulations showed pH dependent drug release with a slow and sustained release profile. Slower drug release was observed from sterically stabilized emulsomes than the plain emulsomes. The drug release profile followed the Higuchi model with the Fickian diffusion pattern. The Pegylation of emulsomes significantly reduced the <em>in vitro</em> protein absorption.</p> <p><strong>Conclusion: </strong>The sterically stabilized emulsome can serve as a novel non-toxic platform with longer circulatory time for the delivery of Paclitaxel and other poorly water-soluble drugs as well.</p> S. DUBEY S. P. VYAS Copyright (c) 2021 Surbhi Dubey, S.P. Vyas 2021-03-07 2021-03-07 114 121 10.22159/ijap.2021v13i2.40339 SETTING TIME, FLOWABILITY, AND SOLUBILITY OF EPOXY RESIN-BASED SEALER MIXED WITH CHITOSAN NANOPARTICLES <p style="text-align: justify; margin: 6.0pt 0in 6.0pt 0in;"><strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">Objective: </span></strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">The purpose of this study was to investigate the effect of the incorporation of chitosan nanoparticles into epoxy resin-based sealer on its setting time, flowability and solubility.&nbsp;</span></p> <p style="text-align: justify; margin: 6.0pt 0in 6.0pt 0in;"><strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">Methods: </span></strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">This study was divided into three evaluations: setting time, flowability, and solubility of sealers. Each study used 20 samples, which were divided into two groups. Group 1, epoxy resin-based sealers, and group 2, epoxy resin-based sealers mixed with chitosan nanoparticles. The Gilmore needle was used to observe the setting time, a simple press method based on ISO 6876 was employed to evaluate the flowability of the sealer, and the solubility test, which was according to ISO 6876 standard, was used to determine the solubility of sealers. The surface structure of the sealers before and after the solubility test was observed under Scanning Electron Microscopy (SEM). The data obtained from each study were analyzed by an unpaired t-test with a degree of significance of 95%.</span></p> <p style="text-align: justify; margin: 6.0pt 0in 6.0pt 0in;"><strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">Results: </span></strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">The results showed that the setting time of epoxy resin and epoxy resin incorporated with chitosan were 567<strong><span style="font-family: 'Cambria','serif';">±</span></strong>30.20 and 572.5<strong><span style="font-family: 'Cambria','serif';">±</span></strong>27.91 min, flowability was 25.06±0.89 and 23.18±1.06 mm, and solubility was 0.0051%±0.0016 and 0.0045%±0.0018, respectively. No significant difference occurred between epoxy resin-based sealer and epoxy resin-based sealer mixed with chitosan nanoparticles in setting time, flowability, and solubility of sealers (*P&gt;0.05).&nbsp;</span></p> <p style="text-align: justify; margin: 6.0pt 0in 6.0pt 0in;"><strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">Conclusion: </span></strong><span style="font-size: 8.0pt; font-family: 'Cambria','serif';">The incorporation of chitosan nanoparticles produced a similar effect in setting time, flowability, and solubility as the epoxy resin-based sealer. Thus, epoxy resin-based sealer mixed with chitosan nanoparticles had acceptable properties in setting time, flowability, and solubility based on ISO 6876 standards. </span></p> DIATRI NARI RATIH RARAS AJENG ENGGARDIPTA ADI NUGROHO HENDRO KUSUMO WIGNYO HADRIYANTO Copyright (c) 2021 Diatri Nari Ratih, Raras Ajeng Enggardipta, Adi Nugroho Hendro Kusumo, Wignyo Hadriyanto 2021-03-07 2021-03-07 122 126 10.22159/ijap.2021v13i2.40270 FORMULATION AND EVALUATION OF SOLID SELF MICRO EMULSIFYING DISPERSIBLE TABLET OF PIROXICAM <p><strong>Objective: </strong>The aim of this study was to formulate the solid self-micro emulsifying dispersible tablets for promoting the dissolution of Piroxicam.</p> <p><strong>Methods: </strong>Solubility study test was performed to know the solubility of various oil phase, surfactants, cosurfactants. Self-emulsifying grading test was done by visual grading system. Ternary phase diagrams and droplet size analysis test were performed to screen and optimize the Piroxicam-self microemulsifying drug delivery system (SMEDS). Then microcrystalline cellulose (KG802) was added as a suitable adsorbent and dispersible tablet were prepared by wet granulation compression method.</p> <p><strong>Results: </strong>The final composition of Piroxicam-SMEDS was oil phase (oleic acid, 23%), surfactant (Cremophor R H-40,61%), co-surfactant (PEG-400,16%) based on the result of solubility test, self-emulsifying grading test, droplet size analysis and ternary phase diagrams. Microcrystalline cellulose (KG802) was selected based on dissolution study (98.35%) and added to liquid Piroxicam-Smeds formulation to form dispersible tablets. The <em>in vitro </em>dissolution study showed 98.02 % of drug release from Piroxicam-SMEDS tablets.</p> <p><strong>Conclusion: </strong>Piroxicam–Self microemulsifying dispersible tablets have increased the solubility and bioavailability of the Piroxicam to a greater extent. SMEDS formulation can help the solubility of poorly water-soluble drugs. </p> GIRISH S. H. SURABHI C. SATHISH BABU P. MEENAKSHI S. SIDDARAMAIAH NITHIN K. S. D. V. GOWDA Copyright (c) 2021 GIRISH SH, AFRASIM MOIN, SURABHI C, MEENAKSHI S, SIDDARAMAIAH, SATHISHBABU, NITHIN K S, DV Gowda 2021-03-07 2021-03-07 127 133 10.22159/ijap.2021v13i2.40238 AUTHENTICATION OF SPRAGUE DAWLEY RATS (RATTUS NORVEGICUS) FAT WITH GC-MS (GAS CHROMATOGRAPHY-MASS SPECTROMETRY) COMBINED WITH CHEMOMETRICS <p><strong>Objective</strong>: Misuse of rat meat as food worried people. Rat meat can come from research waste; one of the rats used in the research was the <em>Sprague Dawley</em>. Analysis of rat meat in food can be done using fat. The aim of this study was to authenticate rat fat with GC-MS combined with chemometrics.</p> <p><strong>Methods</strong>: The meat of <em>Sprague Dawley</em> rats, wild boar, goats, cow, and processed meatballs was put in the oven at 90-100 °C for±one hour, then derivatized with BF<sub>3</sub> and NaOH in methanol to get the methyl ester for injected in GC-MS instrument. The results obtained were in the form of chromatograms and spectrograms. The data was processed using Principal Component Analysis (PCA) to grouping rat's meat with others (wild boars, goats, cows, and processed meatballs).</p> <p><strong>Result</strong><strong>s</strong>: Rat meat fatty acid analysis results with GC-MS were obtained oleate (43.32±1.43)%, linolenate (32.24±1.46)%, palmitate (19.75±0.09)%, palmitoleate (1.14±0.06)%, stearate (0.26±0.01)%, myristate(0.18±0.01)%, margarate (0.15±0.02)%, and pentadecanoate (0.14±0.01)%. The PCA chemometrics results showed that rat meats had scores that close to cows, which meant they had similar fatty acid composition.</p> <p><strong>Conclusion</strong>: The GC-MS method, combined with PCA chemometrics, tested rat fat with other animals and processed meatballs samples on the market.</p> ANY GUNTARTI KARINA PRIMATYAS NINGRUM IBNU GHOLIB GANDJAR NINA SALAMAH Copyright (c) 2021 Any Guntarti, Karina Primatyas Ningrum, Ibnu Gholib Gandjar, Nina Salamah 2021-03-07 2021-03-07 134 139 10.22159/jap.2021v13i2.40130 DEVELOPMENT AND VALIDATION OF AN ANALYTICAL METHOD FOR THE DETERMINATION OF METHYLISOTHIAZOLINONE AND METHYLCHLOROISOTHIAZOLINONE IN COSMETIC PRODUCTS USING MATRIX SOLID-PHASE DISPERSION COUPLED TO GAS CHROMATOGRAPHY-MASS SPECTROMETRY <p><strong>Objective: </strong>This study was to develop the first simultaneous method for quantification of MI and MCI by using matrix solid-phase dispersion (MSPD) as an extraction technique followed by gas chromatography-tandem mass spectrometry (GC-MS) in cosmetic products to support that law enforcement.</p> <p><strong>Methods: </strong>The MI and MCI were extracted from the cosmetic sample by using matrix solid-phase dispersion technique with alumina as solid sorbent and ethyl acetate as eluent. After being isolated, MI and MCI from the samples were analyzed using GC-MS equipped with DB-5MS capillary column.</p> <p><strong>Results: </strong>The validated method for both leave-on and rinse-off cosmetic showed that MI and MCI recoveries were between 97.87-103.15 %, relative standard deviation (RSD) values were lower than 11%, and limit of quantitation (LOQ) values for the leave-on product were 0.96 µg/ml and 1.95 µg/ml and for rinse-off products were 0.56 µg/ml and 1.49 µg/ml for MI and MCI, respectively.</p> <p><strong>Conclusion: </strong>This purposed analytical method for determining MI and MCI in cosmetic products using MSPD-GC-MS complies with the validation acceptance criteria.</p> NURINA PRAPURANDINA HARMITA HARMITA HERMAN SURYADI Copyright (c) 2021 Harmita Harmita, Herman Suryadi, Nurina Prapurandina 2021-03-07 2021-03-07 140 147 10.22159/ijap.2021v13i2.40058 DEVELOPMENT AND VALIDATION METHOD OF CYCLOPHOSPHAMIDE AND 4-HYDROXYCYCLOPHOSPHAMIDE WITH 4-HYDROXYCYCLOPHOSPHAMIDE-D4 AS INTERNAL STANDARD IN DRIED BLOOD SPOTS USING UPLC-MS/MS <p><strong>Objective: </strong>Cyclophosphamide (CP) is anticancer of the alkylating agent (nitrogen mustard) and a prodrug which will be metabolized into an active metabolite form, 4-hydroxycyclophosphamide (4-OHCP). Therefore, the effectiveness of therapy with CP is determined by its metabolites concentration. The purpose of this study was to obtain a validated analytical method of CP and 4-OHCP simultaneously and sensitively in dried blood spots with SIL (Stable Isotope Labeled) 4-OHCP-d<sub>4</sub> as the internal standard using liquid chromatography-tandem mass spectrometry, so optimization and full validation are conducted in this research.</p> <p><strong>Methods: </strong>A simpler analytical method was developed and validated to quantify CP and 4-OHCP in DBS samples using an Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). A linear regression was used as the statistical analysis method. Sample preparation was performed by protein precipitation using methanol. The separation was performed on UPLC H-Class BEH C18 column using formic acid 0.01%-acetonitrile as the mobile phase in gradient mode at 0.2 ml/minute. The mass detection was performed on Waters Xevo TQD using ESI+for CP, 4-OHCP-SCZ, and IS 4-OHCP-d4-SCZ with m/z value: 261.03&gt;140.16; 334.10&gt;221.04; and 338.10&gt;225.06.</p> <p><strong>Results: </strong>This method was linear within the range of 10–40,000 ng/ml for CP and 5–4,000 ng/ml for 4-OHCP. Lower Limit of Quantification (LLOQ) concentration of CP was 10 ng/ml and 4-OHCP was 5 ng/ml.</p> <p><strong>Conclusion: </strong>This method has successfully fulfilled the validation requirement referring to the 2011 EMA and 2018 FDA guidelines.</p> YESI IHDINA FITYATAL HASANAH YAHDIANA HARAHAP HERMAN SURYADI Copyright (c) 2021 Yahdiana Harahap, Yesi Ihdina Fityatal Hasanah 2021-03-07 2021-03-07 148 152 10.22159/ijap.2021v13i2.39590 PREPARATION AND CHARACTERIZATION OF LOW MOLECULAR WEIGHT CHITOSAN WITH DIFFERENT DEGREES OF DEACETYLATION BY THE ACID HYDROLYSIS METHOD <p><strong>Objective</strong>: The objective of this research is to prepare Low Molecular Weight Chitosan (LMWC) by the acid hydrolysis method, using dilute hydrochloric acid (2M). LMWC has superior properties compared to the High Molecular Weight Chitosan (HMWC), especially in terms of water solubility, antibacterial and antifungal properties. These could open new potential applications for LMWC in sectors such as the cosmetics, food, and pharmaceutical industries.</p> <p><strong>Methods: </strong>In this work, the acid hydrolysis method was used to produce LMWC with different molecular weights starting from 500 kDa and 93% degree of deacetylations (DDA). The molecular weights of the produced grades were determined by applying Mark-Houwink equation while the %DDA was determined and verified by the use of the 1<sup>st</sup> derivative UV method and <sup>1</sup>HNMR method, respectively. The depolymerization reactions were carried out with different time intervals to produce totally deacetylated LMWC of 30 kDa, 15 kDa, and 7.5 kDa. The LMWC was characterized by FTIR, XRD, and DSC to evaluate the functionality, microstructure and thermal properties.</p> <p><strong>Results: </strong>The FTIR spectra revealed that there is no significant difference in the main skeletal structure of the LMWC and HMWC. On the other hand, the XRD and DSC results showed that the LMWC of different molecular weights and degrees of deacetylation are of semi-crystalline structure, similar to the HMWC.</p> <p><strong>Conclusion: </strong>The obtained results showed that the used acid hydrolysis procedure can produce LMWC grades of desired specifications, yields, and quality which are suitable for use in different applications.</p> NAWZAT D. AL-JBOUR M. D. H. BEG JOLIUS GIMBUN A. K. M. MOSHIUL ALAM Copyright (c) 2021 Nawzat Deeb Aljbour, Mohammad Dalour Hussen Beg, Jolius Gimbung 2021-03-07 2021-03-07 153 164 10.22159/ijap.2021v13i2.32229 A NEW HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE SEPARATION AND SIMULTANEOUS QUANTIFICATION OF EPTIFIBATIDE AND ITS IMPURITIES IN PHARMACEUTICAL INJECTION FORMULATION <p><strong>Objective: </strong>The objective of the present study is to develop a stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for qualitative and quantitative determination of Eptifibatide and its impurities in bulk and pharmaceutical dosage forms.</p> <p><strong>Methods: </strong>The chromatographic separation was carried on Phenomenex Luna C18 column (250 mm×4.6 mm; 5µ id) as stationary phase, methanol and phosphate buffer at pH 6.4 in the ratio of 65:45 (v/v) as mobile phase at flow rate of 1.0 ml/min, Ultra Violet (UV) detection was carried at the wavelength of 236 nm and the analysis was completed with a run time of 15 min.</p> <p><strong>Results: </strong>In the developed conditions, the retention time of Eptifibatide and its impurities 1 and 2 were found to be 3.35, 4.93 and 8.18 min, respectively. The method was validated for system suitability, range of analysis, precision, specificity, stability and robustness. Spiked recovery at 50%, 100% and 150% was carried for both standard and impurities and the acceptable % recovery of 98-102 was observed for Eptifibatide and both impurities studied and the % Relative standard deviation (RSD) in each spiked level was found to be less than 2. Stability tests were done through the exposure of the analyte solution to five different stress conditions i. e expose to 1N Hydrochloric acid (HCl), 1 N Sodium hydroxide (NaOH), 3% Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), 80 °C temperature to UV radiation. In all the degradation conditions, standard drug Eptifibatide was detected along with both the impurities studied and the degradation products were successfully separated. In the formulation analysis, there is no other chromatographic detection of other impurities and formulation excipients.</p> <p><strong>Conclusion: </strong>The developed method was found to be suitable for the quantification of Eptifibatide and can separate and analyse impurities 1 and 2.</p> K. SRI GIRIJA BIKSHAL BABU KASIMALA VENKATESWARA RAO ANNA Copyright (c) 2021 Venkateswara Rao Anna, Sri Girija K, Bikshal babu Kasimala 2021-03-07 2021-03-07 165 172 10.22159/ijap.2021v13i2.39895 IN SILICO STUDIES ON DIACYL DERIVATIVES OF PHLOROGLUCINOL TO ENHANCE PHARMACODYNAMIC AND PHARMACOKINETIC PROFILES OF 2,4,6-TRIHYDROXY-3-GERANYL-ACETOPHENONE <p><strong>Objective: </strong>The purpose of this study was to evaluate the LOX inhibitory activity, and predict the drug likeness properties of designed diacyl derivatives of phloroglucinol, using <em>in silico</em> method.</p> <p><strong>Methods: </strong>The designed derivatives were subjected to molecular docking using AUTODOCK while the receptor used in this study was built from SWISS MODEL. Drug likeness properties of the derivatives were calculated by online programs i.e. MOLINSPIRATION and PreADMET.</p> <p><strong>Results: </strong>Molecular docking study revealed that designed tHGA derivative with four-carbon chain length exhibited the best binding affinity with the docking scores of -7.26kcal/mol. Three types of binding interactions were observed between the derivatives and the receptor site i.e H-bonding, hydrophobic and Van der Waals interactions. The important amino acid residues involved in H-bonding were Gln495 and Gln697, while other amino acid residues, such as Leu754 and Ile 553, were involved in the Van der Waals interaction. The designed tHGA derivatives were mainly stabilized through hydrophobic interactions with His499, His504, Ile538, Phe557 and Val750. <em>In silico</em> physicochemical calculations predicted that all the designed derivatives passed the Lipinski’s Rule of 5, and have good human intestinal absorption property (HIA&gt;70%). Further, all the designed derivatives showed moderate central nervous system absorption (0.6&lt;BBB&lt;2.0), except for the derivative with a longer (5-Cs) chain length.</p> <p><strong>Conclusion: </strong>The findings of the present study suggested that changing the acyl and geranyl side chains of the natural product molecule, tHGA, into two acyl bearing side chains, will improve its pharmacodynamic and pharmacokinetic profiles.</p> SHEAU WEI CHIONG CHEAN HUI NG KHOZIRAH SHAARI Copyright (c) 2021 Sheau Wei Chiong, Chean Hui Ng, Khozirah Shaari 2021-03-07 2021-03-07 173 179 10.22159/ijap.2021v13i2.40784 PREPARATION AND EVALUATION OF COPPER NANOPARTICLES LOADED HYDROGEL FOR BURNS <p><strong>Objective: </strong>The present study focuses on the development and optimization of copper nanoparticles (CNPs) loaded hydrogel for the treatment of dermal burn injuries.</p> <p><strong>Methods: </strong>CNPs gel was prepared by dispersing the variable concentration of polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC) in distilled water, PEG 400, and copper nanoparticles. factor screening study was performed for identification of influential factors, followed by optimization study using three-factor Box-Behnken design.</p> <p><strong>Results: </strong>Optimized nanogel formulation, when compared to normal control (NC), shows a significant reduction of pro-inflammatory cytokines (IL-6 = 39.74 % and TNF-α =49.37%) and increased level of anti-inflammatory cytokines (IL-10 = 30.90%), indicating reduced inflammation. Further, the wound closure rate of CNPs gel shows significant (12.27 %) wound closure as compared to the NC group and complete wound closure (100 %) on the 14th day, indicating accelerated wound healing.</p> <p><strong>Conclusion: </strong>the present investigation endorses accelerated scar-free, accelerated wound healing potential of copper nanoparticles gel with anti-inflammatory potential.</p> ASHISH KUMAR VINAY PANDIT UPENDRA NAGAICH Copyright (c) 2021 Ashish Kumar, vinay Pandit, Upendra Nagaich 2021-03-07 2021-03-07 180 189 10.22159/ijap.2021v13i2.40558 DESIGNING AND OPTIMIZATION OF NAPROXEN SODIUM DEFORMABLE VESICULAR SYSTEMS THROUGH FACTORIAL DESIGN: BOX BEHENKEN MODEL <p><strong>Objective: </strong>The objective of this investigation was to develop and statistically optimize deformable vesicles such as transfersomes and transethosomes of Naproxen sodium by employing 3<sup>3</sup>factorial designs through software Design expert version 12 (Box–Behnken design) for dermal delivery.</p> <p><strong>Methods: </strong>The levels of the drug, phosphatidylcholine, and span 80 (independent variables) were varied to study the influence on vesicle size and % entrapment efficiency (dependent variables) of transfersomes and for transethosomes, the levels of phosphatidylcholine, ethanol, and span 80 were selected as independent variables Second-order quadratic polynomial equation, 2D and 3D contour plots represented the relationship between variables and desired response. The optimization process was carried out using desirability plots and point prediction techniques.</p> <p><strong>Results: </strong>Results of the present study demonstrated that optimized transfersomes and transethosomes showed vesicle sizes of 114.91 nm and 102.91 nm respectively, while entrapment efficiency of 80.11 % and 86.97%, respectively. Both formulations showed high zeta potential values indicating the stability of the optimized formulation. ANOVA statistical results showed a significant difference (P&lt;0.05).</p> <p><strong>Conclusion: </strong>The results indicated that the independent variable plays a crucial role in optimizing a formulation that can be used for further research studies. Present preliminary study data provided strong evidence that the optimized deformable vesicular formulations through box Behnken factorial design can be a potentially useful drug carrier for naproxen sodium dermal delivery with minimum vesicle size and efficient entrapment efficiency.</p> NAVEEN GUPTA SHAILESH JAIN Copyright (c) 2021 Naveen Gupta 2021-03-07 2021-03-07 190 197 10.22159/ijap.2021v13i2.40398 The THE ANTICHOLESTEROL ACTIVITY OF BETULINIC ACID AND STIGMASTEROL ISOLATED FROM THE LEAVES OF SUNGKAI (PARONEMA CANESCENS JACK) <p><strong>Objective: </strong>The purpose of this study was to evaluate the anticholesterol activity of <em>Paronema canescens</em> leaves extract.</p> <p><strong>Methods</strong>: These compounds were isolated via chromatography using silica gel as the stationary phase. Their structures were revealed using IR and 1D NMR data and by comparing their NMR data with the literature's data. The anticholesterol activity of compounds was tested using photometry via the Liebermann–Burchard reaction.</p> <p><strong>Results: </strong>Betulinic acid (1) and stigmasterol (2) were isolated from the leaves extracts of <em>sungkai</em> (<em>P. canescens</em>). The betulinic acid (1) that was isolated showed anticholesterol activity with an IC<sub>50</sub> value of 60.53 µg/ml, stigmasterol (2) 222.32 µg/ml, while the standard anticholesterol compound simvastatin had an IC<sub>50</sub> of 24.68 µg/ml.</p> <p><strong>Conclusion</strong>: The stigmasterol (2) has previously been reported from <em>P. canescens</em> while that of betulinic acid (1) is reported here for the first time and identifies its anticholesterol activity. </p> MUHARNI MUHARNI FERLINAHAYATI FERLINAHAYATI HENI YOHANDINI FAHMA RIYANTI NADYA ANASTASIA PRESCILLA PAKPAHAN Copyright (c) 2021 Muharni Muharni 2021-03-07 2021-03-07 198 203 10.22159/ijap.2021v13i2.40372 SILVER NANOPARTICLES AND COCONUT OIL INCORPORATED BIOPOLYMER BASED ELECTROSPUN NANOFIBERS FOR WOUND DRESSING <p><strong>Objective: </strong>The main aim of this study was to develop and evaluate the nanofiber loaded with coconut oil and silver nanoparticles (Ag NPs) for the treatment of wound healing by the electrospun method.</p> <p><strong>Methods: </strong>The nanofibers have been created using the reduced form of silver nanoparticles and coconut oil along with Eudragit L-100 by the electrospun method. The presence of coconut oil and chemical interaction was determined by the FTIR method. XRD was made to evaluate the crystalline nature of AgNPs and Eudragit L-100. TEM was carried out to show the presence of AgNPs on the surface of nanofibers and SEM represents the diameter of the fiber. The antibacterial activity of nanofibers was carried out using a disk diffusion assay.</p> <p><strong>Results: </strong>The diameter of the fibers was diminished by the excess of AgNPs in the fibers, while it increases by the coconut&nbsp;oil concentration, enhancing the nanofiber's hydrophilicity. FTIR spectroscopy was found in the range of coconut oil at 3553 cm<sup>-1</sup>for O-H stretch, 1365 cm<sup>-1,</sup> and 1240 cm<sup>-1</sup> for the C-O stretch of ester groups. The diffraction peaks at 2θ of 38.5°, 44.6°, and 64.7°, in the XRD spectra of nanofiber, changed with silver NP affirming the total decrease of Ag salt. The bactericidal activity has been carried out between <em>Escherichia coli</em> and <em>Staphylococcus aureus </em>showing zones of inhibition of 20.0±0.2 mm and 14.8±0.4 mm, exhibiting excellent bactericidal characteristics for wound healing.</p> <p><strong>Conclusion: </strong>The formulated nanofibers were obtained to offer protection against external agents and help in the regeneration of new tissue.</p> SUBHASHREE SAHOO JOGABRATA TRIPATHY AFRASIM MOIN MEENAKSHI S. SIDDARAMAIAH D.V. GOWDA Copyright (c) 2021 SUBHASHREE SAHOO, JOGABRATA TRIPATHY, AFRASIM MOIN, MEENAKSHI S, SIDDARAMAIAH, D.V. GOWDA 2021-03-07 2021-03-07 204 209 10.22159/ijap.2021v13i2.40291 DEVELOPMENT OF LIQUISOLID FORMULATION FOR IMPROVED SUSTAINED RELEASE OF PROPRANOLOL HYDROCHLORIDE <p><strong>Objective: </strong>The aim of this study was to develop a liquisolid formulation of propranolol hydrochloride to obtain an improved sustained release profile by varying the ratio of liquid vehicles.</p> <p><strong>Methods: </strong>In this study, propranolol hydrochloride (PPH) was dispersed in the combination of propylene glycol and polysorbate 80, as the liquid vehicles, with different ratios. Eudragit<sup>®</sup> RL and Aerosil<sup>®</sup> were used as carrier and coating materials, respectively, to produce a dry and free-flowing powder. In addition, HPMC was used to amplify the retardation effect. The prepared formulations were evaluated for its physicochemical properties, including loss on drying, flow rate, angle of repose calculation, drug content analysis, FT-IR spectroscopy, as well as dissolution studies. The obtained dissolution profiles were subsequently fitted to the mathematical model in order to determine the drug kinetics.</p> <p><strong>Results: </strong>The results show that all formulations performed dry and free-flowing granules containing PPH in the range of 7-9%. Furthermore, all the prepared formulations were able to sustain the drug release for a total of 8 h in two different dissolution media, namely simulated gastric fluid and simulated intestinal fluid. F4 containing propylene glycol and polysorbate 80 (1:2) possessed the lowest drug release rate. It was also obtained that F1 and F3 followed first-order kinetics while F2, F4, and F5 complied with the Higuchi model.</p> <p><strong>Conclusion: </strong>Overall, there was no difference in all the dissolution profiles based on the calculation of the difference and similarities factor.</p> ALIYAH ALIYAH EMILIA UTOMO ANDI DIAN PERMANA ERNAWATI Copyright (c) 2021 Aliyah Aliyah, Emilia Utomo, Andi Dian Permana, Ernawati 2021-03-07 2021-03-07 210 216 10.22159/ijap.2021v13i2.40354 IMPROVEMENT AND ESTIMATION OF ORALLY DISINTEGRATING TABLETS CONTAINING PILOCARPINE 2-HYDROXY PROPYL β-CYCLODEXTRIN INCLUSION COMPLEX BY RESPONSE SURFACE METHODOLOGY <p><strong>Objective: </strong>The study aimed to develop and evaluate an orally disintegrating tablet that contains pilocarpine and 2-hydroxy propyl β-cyclodextrin as an inclusion complex that is prepared by lyophilization used for treatment for dry mouth. Pilocarpine is utilized to treat dry mouth disorder. The inclusion complex lowers the taste of pilocarpine through the oral mucosa by the use of 2-hydroxy propyl β-cyclodextrin.</p> <p><strong>Methods</strong>: The <em>in vitro</em> release from the insertion complex is also been studied. The parameters like differential scanning calorimetry (DSC), Fourier transformer infrared spectroscopy (FTIR), X-ray diffraction (XRD), and morphological study have been evaluated. The design of an experiment is carried out based on the concentration of croscarmellose sodium (CCS) and microcrystalline cellulose (MCC). Evaluation of the prepared orally disintegrating tablets have been carried out by different test methods like weight variation, thickness, drug content, disintegration, and <em>in vitro</em> dissolution study.</p> <p><strong>Results: </strong>Orally disintegrating tablets are studied by utilizing the immediate pressure technique. Pilocarpine indicates the anhydrous crystalline medication, displaying sharp endothermic top at 120.2 °C, bend of 2-HPβCD demonstrates an exceptionally wide endothermal wonder among 55-100 °C for DSC. In pilocarpine spectra, characteristic band of aromatic C-H stretch at 3277 cm<sup>-1</sup>, C=C stretching at 1608 cm<sup>-1</sup>, C-N stretching at 1445 cm<sup>-1 </sup>and methoxy (CH<sub>3</sub>-O-) stretch at 2921 cm<sup>-1 </sup>was observed. The investigation shows that tablet hardness of 4.3N, breaking downtime of 12 sec and mean disintegration time is 1.562 min.</p> <p><strong>Conclusion: </strong>The different diluents and super disintegrating have been applied for the quick elevation of dry mouth that helps us for patient compliance.</p> JOGABRATA TRIPATHY SUBHASHREE SAHOO AFRASIM MOIN SIDDARAMAIAH D. V. GOWDA Copyright (c) 2021 Jogabrata Tripathy, SUBHASHREE SAHOO, AFRASIM MOIN, SIDDARAMAIAH, D V GOWDA 2021-03-07 2021-03-07 217 223 10.22159/ijap.2021v13i2.40292 IBUPROFEN LOADED ORGANOGEL: DEVELOPMENT AND CHARACTERIZATION <p><strong>Objective: </strong>This study aimed to develop and <em>in vitro</em> characterize an organogel (<em>OG</em>) loaded Ibuprofen.</p> <p><strong>Methods: </strong>Organogel (<em>OG</em>) composed of water, isooctane, sorbitan esters, sorbitan monopalmitate (Span-40), and poly(oxyethylene) sorbitan monostearate (Polysorbate-60) was loaded with Ibuprofen. The partial phase behavior of ibuprofen <em>OG</em> was studied to optimize the formulation composition. 1.0% w/w Ibuprofen loaded <em>OG </em>were characterize for rheological, <em>in vitro</em> release and stability study.</p> <p><strong>Results: </strong>Phase diagram showed an isotropic gel region at low water contents, which converted to emulsion on increasing water quantity. The rheological properties of the <em>OG</em> incorporating 1.0% w/w Ibuprofen shows the presence of two Tg’s and elastic behavior of gel, reflects the presence of an entangled network of aqueous tubules. The fractal dimension <em>d</em><sub>f</sub> value of 2.1 and 2.3 was obtained for the two curves (elastic and storage modulus), which is indicative of the formation of the densest gel structure. The diffusional release exponent (<em>n</em>) was found to be ~0.7 (0.5&lt;<em>n</em>&lt;1), which is indicative of non-Fickian, anomalous diffusion of the drug from the <em>OG</em>. The <em>in vitro</em> drug release exhibited release @ 7.04%/h 0.7/cm<sup>2</sup> from the <em>OG</em>. Ibuprofen containing <em>OG</em> was stable for 28 d in terms of chemical potency and gel stiffness at 4 °C and room temperature (~25 °C).</p> <p><strong>Conclusion</strong>: The study indicates the potential of <em>OG</em> for improved transdermal delivery of Ibuprofen.</p> CHANDRA PRABHA UPADHYAY MEENAKSHI BHARKATIYA Copyright (c) 2021 meenakshi bharkatiya meenakshi 2021-03-07 2021-03-07 224 227 10.22159/ijap.2021v13i2.40108 MASTIC-G-POLY (ACRYLAMIDE): MICROWAVE-ASSISTED SYNTHESIS AND CHARACTERISATION <p><strong>Objective: </strong>The objective of the present investigation was the synthesis of grafted co-polymer gum mastic using acrylamide as the monomer.</p> <p><strong>Methods: </strong>3-factor 3-level response surface Box-Behnken design, which requires 15 runs including three replicates of the central run, was used for the synthesis of graft copolymers of mastic gum with acrylamide using ceric ammonium nitrate as the free radical initiator. The critical synthesis and process parameters; CSPP (A = concentration of monomer, B = concentration of initiator and C= Temperature) to generate design space and optimize formulation with an aim to obtain critical quality attributes (CQA, Y1 =% Yield, Y2 =% Grafting, Y3 =% grafting efficiency).</p> <p><strong>Result: </strong>Formulation F14 having a maximum % yield of 75.89% with % grafting of 210% and % grafting efficiency 51.57% was selected as best.</p> <p><strong>Conclusion: </strong>The microwave-assisted grafted mastic gum was prepared successfully and optimized by using Box Behnken design.</p> MOHIT KUMAR SURAJPAL Copyright (c) 2021 Mohit Kumar Mehta 2021-03-07 2021-03-07 228 234 10.22159/ijap.2021v13i2.40551 DEVELOPMENT AND OPTIMIZATION OF MANNOSYLATED NARINGENIN LOADED TRANSFERSOMES USING RESPONSE SURFACE METHODOLOGY FOR SKIN CARCINOMA <p><strong>Objective: </strong>The flavonoidal drug Naringenin offers a natural defense against free radical generation due to their antioxidant i.e. free radical scavenging property. The continuation of research work towards the invention of targeting the flavonoidal drug for skin carcinoma. Naringenin is a potent antioxidant, having remarkable reactive oxygen species scavenging potential and abundantly found in citrus fruits.</p> <p><strong>Methods: </strong>The optimization of the formulated mannosylated naringenin-loaded transfersomes (MA-NgTfs) was performed using Box–Behnken statistical design to obtain crucial variable parameters that influence vesicular size, size distribution and surface charge. Therefore keeping both the concepts in mind our objective is to design and optimize the mannosylated naringenin loaded transfersomes (MA-NgTfs) for macropahge targeting. The Box Behnken with 3D surface response design graph was employed to optimize the formulation.</p> <p><strong>Results: </strong>Phospholipids and surfactant ratio played a remarkable role to determine the mean vesicular size and the Zeta potential of the vesicles. The Zeta potential is found in the formulation having a range of-18.01±1.05 to-28.7±1.008 mV represents the good stability of the formulation. The vesicles size range was found in the range of 102.4±1.01 to 263.74±0.63 and range of Entrapment efficiency of nanovesicles was as 72.04±1.53 to 82.04±0.81. <em>In vitro</em> drug release study shows that mannosylated naringenin loaded transfersomes (MA-NgTfs), and marketed formulation dispersion was found 69.31 %, 62.03 %, 58.71 %, and 65.02 % respectively. <em>Ex vivo</em> skin permeation and deposition study shows that the marketed product and pure drug suspension optimized transfersomes through the skin of mice was of flux 6.5±3.07 and the percentage of drug retention was 0.76±1.26. The results gave us strong evidence of cellular uptake bymannose–directed transfersomes via mannose receptor-based endocytosis.</p> <p><strong>Conclusion: </strong>On the basis of findings, the study revealed that the prepared formulation has characteristic potential for targeting and the concept of ligand directed nanocarrier formulation was imparts synergistic effect against UV-induced skin carcinoma.&nbsp;</p> NIKITA VERMA SWARNLATA SARAF Copyright (c) 2021 sachinkumarjain jain 2021-03-07 2021-03-07 235 241 10.22159/ijap.2021v13i2.40436 DESIGN EXPERT SUPPORTED FORMULATION DEVELOPMENT, MATHEMATICAL OPTIMIZATION AND PREDICTABILITY STUDY OF FLOATING TABLETS OF BISOPROLOL FUMARATE <p><strong>Objective: </strong>Focus of the study was to formulate Design expert Software assisted floating tablet of Bisoprolol Fumarate. Bisoprolol Fumarate is a Beta adrenergic blocking agent, used to treat cardiac diseases favorable characters to be formulated as sustained release Gastro retentive floating tablets.</p> <p><strong>Methods: </strong>Floating Tablets of Bisoprolol Fumarate were prepared by using polymers such as Polyox N 12 K and Carbapol 940 P. Formulations were prepared by using direct compression method and evaluated for various parameters like Hradness, thickness, weight variations, Floating lag time Total floating time,% drug release and Stability Study etc.</p> <p><strong>Results: </strong>FTIR spectroscopic study indicates no drug-excipients interaction in the prepared formulations. Hardness or crushing strength of the tablets of all the formulation was found between 5.8 and 6.5 kg/cm<sup>2. </sup>Floating lag time of all batches is in range of 1.18±2.0 to 2.43±1.6 (minutes). All other parameters of all batches are within an acceptable range. The polymer Carbopol 940 P had the significant negative effect of on the floating lag times. The <em>In vitro</em> dissolution profiles of optimized A3 Floating formulation of Bisoprolol Fumarate were found to sustain drug release 99.25 % up to 12 h with floating lag time of 1.45 min; Designed formulation was stable after Stability study. Optimization study was carried out by using 3<sup>2</sup>&nbsp;factorial designs to fabricate formulations.</p> <p><strong>Conclusion: </strong>It can be conclude that reproducible results of various parameters in this developed formulation can easily scale up. Furthermore designed formulation will be very effective for controlling blood pressure.</p> SHAIKH SHAOOR AHMAD SHAIKH SIRAJ N. PATEL M. SIDDIK KHALIFA MAHMADASIF YUNUS MAKRANI SHAHARUKH I. SIDDIQI HIFZURRAHMAN MD A. SHAIKH SALMAN ISMAIL Copyright (c) 2021 dr.siraj nawaj shaikh 2021-03-07 2021-03-07 242 248 10.22159/ijap.2021v13i2.40433 FORMULATION AND IN VITRO EVALUATION OF RAMELTEON TABLETS FOR COLON DRUG DELIVERY SYSTEM BY COMPRESSION COATING <p><strong>Objective: </strong>Ramelteon, is a sleep agent that selectively binds to the&nbsp;MT<sub>1</sub>&nbsp;and MT<sub>2</sub>&nbsp;receptors&nbsp;in the&nbsp;suprachiasmatic nucleus (SCN), instead of binding to&nbsp;GABA<sub>A</sub>&nbsp;receptors. In the present research work, the formulation of ramelteon targeted to colon by using various polymers developed.</p> <p><strong>Methods: </strong>Colon-targeted tablets were prepared in two steps. Initially, core tablets were prepared and then the tablets were coated by using different pH dependent polymers. Ethylcellulose, Eudragit RLPO and L100 were used as enteric coating polymers. The precompression blend of all formulations was subjected to various flow property tests and all the formulations were passed the tests. The tablets were coated by using polymers and the coated tablets were subjected to physical characterization, drug content, <em>in vitro</em> drug release and kinetics of drug release.</p> <p><strong>Results: </strong>Among all the formulations, F4 formulation was found to be optimized as it was retarded the drug release up to 18 h and showed maximum of 99.25% drug release. It followed the first-order kinetics mechanism. All the formulations having Korsmeyer-Peppas ‘n’ values are in the range of 0.540 to 0.818. Hence, it was concluded that the prepared formulations followed non-Fickian diffusion.</p> <p><strong>Conclusion: </strong>An effective and stable remelteon colon targeted formulation developed for treating insomnia.</p> TRINADHA RAO M. PARIMALA Y. YAMINI M. PHANINDRA CVS SRINIVASA RAO Y. Copyright (c) 2021 Trinadha Rao Mamidi 2021-03-07 2021-03-07 249 253 10.22159/ijap.2021v13i2.40396 DESIGN AND CHARACTERIZATION OF NANOSPRAY WITH SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM USING SINERGISTIC COMBINATION OF MELASTOMA MALABATHRICUM L. FRACTION AND GENTAMICIN <p><strong>Objective: </strong>This study aimed to design a formula using Design-Expert software to obtain optimal Self-Nanoemulsifying Drug Delivery System (SNEDDS) formulas and to analyze nanospray characteristics of optimal SNEDDS.</p> <p><strong>Methods: </strong>The study began with preparing ethanol extract from <em>Melastoma malabathricum</em>. The extract was then fractionated using ethyl acetate. The formulation design stage began with a solubility test of <em>Melastoma malabathricum</em> fraction and gentamicin (MFG) in various surfactants, co-surfactants and oils. Furthermore, the 14 formula of SNEDDS with various compositions of the selected surfactants, co-surfactants and oils were formulated and evaluated with pH response and emulsification time. Analysis was carried out using Design-Expert software with the simplex lattice design method in order to obtain the optimal formula profile. The pH, emulsification time, particle size, and zeta potential of the nanospray from SNEDDS optimal formulas were physically characterized. Stability of SNEDDS and the nanospray was then tested with freeze-thaw cycling and <em>in vitro</em> diffusion studies with Franz diffusion.</p> <p><strong>Results</strong>: Based on the study, the ratios of optimal formula SNEDDS composition of Tween 80, propylene glycol, and soybean oil were 2.69: 2.64: 1.67 parts. Nanospray with SNEDDS technology had characteristics of pH 5.61±0.16, emulsification time 7.68±0.18, particle size 270.7 nm, and zeta potential-37.20 mV, and it was stable.</p> <p><strong>Conclusion: </strong>Nanospray can be formulated from optimal SNEDDS using Design-Expert software. Nanospray with SNEDDS technology has physical characteristics and is stable. <em>In vitro</em> diffusion studies revealed that the release of <em>Melastoma malabathricum</em> from nanospray was faster than that without preparation.</p> LIZA PRATIWI RAFIKA SARI PRATIWI APRIDAMAYANTI Copyright (c) 2021 liza pratiwi 2021-03-07 2021-03-07 254 263 10.22159/ijap.2021v13i2.40094 COMPARATIVE STUDY OF SEVEN BRANDS OF LEVOFLOXACIN 500 MG FILM-COATED TABLET MARKETED IN YEMEN <p><strong>Objective: </strong>The objective of the current study was to evaluate the quality control parameters of seven brands of levofloxacin 500 mg film-coated tablet available in the Yemeni market.</p> <p><strong>Methods: </strong>Physicochemical parameters assay was performed for seven brands of levofloxacin 500 mg film-coated tablet. Each brand was subjected to official and unofficial <em>in vitro</em> quality control tests, including weight variation, thickness, hardness, friability, disintegration, dissolution, and content uniformity assay by High-Performance Liquid Chromatography (HPLC).</p> <p><strong>Results: </strong>Out of seven, six brands of levofloxacin 500 mg film-coated tablet passed official specified assay tests according to the United States Pharmacopeia (USP) specifications. They showed a similar profile of thickness ranged between±0.01 and 0.10%, friability ranged between 0.01% and 0.34%, disintegration time ranged between 3.00 and 15.00 min, dissolution percentage ranged between 90.650 and 103.05 and content uniformity ranged between 93.62 and 107.12%. Regarding weight variation and hardness, six brands passed the weight variation test and only three brands showed optimum range (10-20 kg) of hardness test. Only one brand failed to pass the weight variation test, and four brands failed to pass the optimum range (10-20 kg) of hardness.</p> <p><strong>Conclusion: </strong>There are no remarkable differences between the seven brands regarding in vitro quality control tests of content uniformity, thickness, friability, disintegration, and dissolution. Even though four brands were above the optimum range of hardiness, they showed complete disintegration and dissolution within the acceptable limit. Regular assessment of marketed drugs is required to ensure bioequivalent to their innovators.</p> GAMIL Q. OTHMAN YASER M. AL-WORAFI MOHAMMED M. BATTAH ABDULSALAM M. HALBOUP HASSAN M. HASSAN Copyright (c) 2021 Mohammed Battah, GAMIL QASEM OTHMAN, ABDULSALAM M. HALBOUP, YASER MOHAMMED AL-WORAF, HASSAN M. HASSAN 2021-03-07 2021-03-07 264 268 10.22159/ijap.2021v13i2.40217 FORMULATION OF GEL FROM GYNURA SEGETUM EXTRACT AND ITS ACTIVITY ON BURN WOUND HEALING <p><strong>Objective</strong>: The aims of this study were to formulate gel from <em>Gynura segetum</em> (GS) extract and evaluate its burn-healing activity.</p> <p><strong>Methods: </strong>GS extract was formulated using carbomer and carboxymethylcellulose (CMC) as a stabilizer with various concentrations. Furthermore, the gel of GS extract was evaluated, including organoleptic, pH and viscosity. A burn-healing evaluation was conducted by making a wound with a hot plate on male Wistar rats, and 600 mg of the gel was applied. Subsequently, the presence of erythema and width contraction of the burns were observed for 15 d.</p> <p><strong>Results: </strong>The result showed that the formulation containing 1 % of carbomer and 1.2 % of GS extract has the best physical stability. The gel also increased the rate of the healing process with decreased burn wound contraction (5.67 mm after 15 d) and the erythema than the control (8.50 mm after 15 d). The significance value was less than 0.05, indicating that the rate of the healing process was significantly different between the GS extract gel and the control.</p> <p><strong>Conclusion: </strong>This finding demonstrated that the gel of GS extract can significantly improve the burns wound healing process and may also be safely used for topical preparation.</p> ARIF BUDIMAN MUHARAM ANIDA CRISTI MAULIDA DIAH LIA AULIFA Copyright (c) 2021 ARIF BUDIMAN, ANIDA CRISTI MAULIDA; diah lia aulifa 2021-03-07 2021-03-07 269 271 10.22159/ijap.2021v13i2.40438