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Glimepiride (GMP) is an oral antidiabetic drug classified as BCS class II, demonstrating extremely limited solubility, with a solubility level below 0.00384 mg/mL. Some generic drug manufacturers producing GMP (copy product) tablets encountered bioavailability issues due to poor dissolution, which did not meet the requirements. Therefore, measures were taken to enhance solubility through the modification of polymorphs. It is known that GMP exists in two polymorphic forms, namely Form I and an alternative Form II, which exhibits higher solubility in water. This study aims to produce and characterize the polymorph-modified GMP compared to non-modified GMP, develop an optimal formulation for polymorph-modified GMP tablets that adhere to pharmaceutical requirements as a representative copy drug model, and determine its similarity factor to Amaryl® as the innovator. The research methodology involved initiating the study by examining the polymorph transformation of GMP through the utilization of techniques such as neat grinding, solvent drop grinding, and solvent evaporation. The resulting samples were characterized using DSC, PXRD, and SEM analysis. The performance assessment encompassed the evaluation of flow properties, compressibility index, solubility, and dissolution rate compared to the non-modified GMP. Based on the characterization results, the best polymorph-modified GMP sample was used to produce a tablet formulation containing 4 mg of GMP using the direct compression method as a copy tablet model. In vitro equivalence testing was performed using a comparative dissolution test on the polymorph-modified GMP tablet compared to its innovator, Amaryl® 4 mg, in three different dissolution media, followed by determining the equivalence status using the similarity factor (f2) calculation. Based on the screening results of polymorph transformation, it was determined that the polymorph-modified GMP, using all three techniques, did not undergo a transition from Form I to Form II. Instead, it underwent amorphization, primarily observed in the solvent evaporation technique. Tablets containing polymorph-modified GMP using the solvent evaporation technique were able to enhance the in vitro dissolution rate profile compared to non-modified GMP tablets. The f2 values for the comparative in vitro dissolution test in acetate buffer pH 4.5 and phosphate buffer pH 6.8 were 60.15 ± 0.27 and 88 ± 0.35, respectively within acceptance criteria of 50–100. However, in KCl/HCl buffer pH 1.2, the f2 value was 45.15 ± 0.23. It was concluded that the polymorph-modified GMP tablet was not similar to its innovator, Amaryl®.

The human body naturally has an antioxidant system to counteract free radical reactivity in a sustainable manner, but if the number of free radicals in the body is excessive, additional antioxidants are needed from food intake, namely vitamin C, vitamin E, carotenes and flavonoids. One plant that has the potential as an antioxidant is Ziziphus spina-christi (ZSC) because it contains phenolics and flavonoids. This study aims to determine the flavonoid content both qualitatively and quantitatively and to test the antioxidant activity of ZSC leaf extract using in vitro and in silico attenuation methods. Determination of the total flavonoid content of ZSC leaf extract using a comparison of quercetin. In vitro the antioxidant activity assay of ZSC leaf extract was carried out by measuring the reducing activity of ZSC leaf extract against the radical DPPH using ascorbic acid as a comparison, while the in silico method used QSAR and pharmacophore modelling techniques. The results showed that the total flavonoid content obtained from ZSC leaf extract was 0.2515 ± 0.0013 mg QE/g D.W with an IC50 of 58.9296 ppm. Furthermore, from the in silico method using pharmacophore modeling and QSAR techniques, 8 hit compounds were obtained from the content of ZSC with IC50 QSAR ranging from 6.57 μM to 0.0004 μM, which was thought to be the metabolite that had the most role in its antioxidant activity. This value indicates that ZSC leaf extract has potential as a very strong antioxidant. ZSC leaf extract can be used as an antioxidant candidate in drug and cosmetic preparations through the oral or percutaneous route. It also proves that QSAR and pharmacophore modelling techniques can be used as confirmatory tests for in vitro results in determining the antioxidant activity of natural materials.

The inclusion complex is one way to enhance active substance solubility, affecting medicine dissolution and penetration. The inclusion complex is formed by utilizing b-cyclodextrin as the host of the active compounds. The Ibuprofen (2-(4-isobutyl-phenyl)propionate) is a propionate acid derivative and classified in class II of the Biopharmaceutic Classification System, which has low dissolutions and high permeability. This study aims to develop a nanogel containing ibuprofen-β-cyclodextrin inclusion complex with the ratio of 1:1, 1:2 and 2:1; and to compare the in-vitro diffusion profile with pure ibuprofen gel. The inclusion complex of ibuprofen-β-cyclodextrin was prepared using the coprecipitation method with the three molar comparison ratio of 1:1, 1:2, and 2:1. The in-vitro study was performed using the gel-based viscolam, comparing the three formulas of ibuprofen-β-cyclodextrin with pure ibuprofen gel. The ibuprofen concentration of each gel tested in the experiment was 1%. The particle size characterization of ibuprofen-β-cyclodextrin inclusion complex gel resulted in having nanoparticle size (510 nm). This characteristic indicates that the inclusion complex gel could enhance the cumulative release amount of ibuprofen compared with pure ibuprofen gel with a relatively smaller particle size (156 nm). Pure ibuprofen and inclusion complex powder size measured to be 763 nm and 957 nm, respectively. The ibuprofen-b-cyclodextrin inclusion complex gel with a molar ratio of 2:1 demonstrated an increase in in-vitro diffusion profile of ibuprofen with a cumulative release amount of 740.3 µg.cm-2. Meanwhile, pure ibuprofen gel had the cumulative release amount of 294.74 µg.cm-2. The gel containing ibuprofen-β-cyclodextrin inclusion complex could enhance the cumulative release amount of ibuprofen compared to pure ibuprofen gel. The ibuprofen-β-cyclodextrin inclusion complex gel at a ratio of 2:1 exhibited an increase in the diffusion of ibuprofen in-vitro.

The COVID-19 has spread worldwide and become an international pandemic. The promising target for drug discovery of COVID-19 was SARS-CoV-2 Main Protease (Mpro), that has been successfully crystallized along with its inhibitor. The discovery of peptide-based inhibitors may present better options than small molecules for inhibitor SARS-CoV-2 Mpro. Natural compounds have such a wide potential and still few explored, Zizyphus spina-christi is one of the medicinal plants that have many pharmacological activities and contains a peptide compound from alkaloids class, i.e. cyclopeptide alkaloids, that is interesting to explore as SARS-CoV-2 Mpro inhibitor. The compound structure was drawn and optimized using density functional theory 3-21G method. The protein chosen was the high resolution of SARS-CoV-2 MPro receptor (1.45 Å) with PDB ID: 6WNP, in complex with boceprevir. Molecular docking simulation was performed using Autodock4 with 100 numbers of GA run, the validation methods assessed by RMSD calculation. Furthermore, the prediction of pharmacological activity spectra was carried out using the PASS Prediction server. The results showed RMSD value was 1.98 Å, this docking method was valid. The binding energy of all compounds showed better results than the native ligand (Boceprevir). The in silico PASS prediction results indicated that all compounds showed antiviral activity. Some compounds showed protease inhibitory activity, i.e Ambiphibine-H, Franganine, and Mauritine-A, and the highest Pa (Predicted activity) value showed by Mauritine-A compounds. It can be concluded that the cyclopeptide compounds of Zizyphus spina-christi were indicated to have a potential as COVID-19 therapy targeting SARS-CoV-2 Mpro.

The role of in silico studies in the discovery of new drugs is very important and interesting in the recent years, where the results can be used as confirmation of the results of in vitro tests carried out experimentally in the laboratory. One of the herbal ingredients is Ziziphus spina-christi leaves with effective antibacterial activity, such as for acne-causing bacteria, namely Propionibacterium acnes. This is because it contains main secondary metabolites with saponins as the major components which contain christinin as its active compound. There are four known types of christinin, namely christinin-A, christinin-B, christinin-C, and christinin-D. In this study, the molecular interaction of the christinin compound was tested to predict its affinity for Propionibacterium acnes compared to clindamycin, as well as to determine the level of safety on the skin so that it can be applied as a topical anti-acne dosage form. In silico studies, including molecular docking and toxicity prediction, were used to assess the activity of four molecules of the christinin compound on c-Jun N-terminal kinase (JNK) macromolecules. The christinin molecules form a strong and stable molecular interaction with the active site of the binding of c-Jun N-terminal kinase (JNK) macromolecules. Interestingly, the christinin compound molecules also has a fairly good level of safety based on the three identified parameters. Based on this results christinin compound molecules has potential to be developed as c-Jun N-terminal kinase (JNK) inhibitors candidate to control of skin infections caused by Propionibacterium acnes which has potential as a topical anti-acne.

Cellulite was identified by the orange-peel appearance of skin surface that presents in 80-90% of post-pubertal women. Caffeine and grape seed oil were known can be used as an anti-cellulite agent. Microemulsion systems are known could enhance the diffusion rate of drugs through the skin. This study was conducted to develop a microemulsion gel containing caffeine and grape seed oil and determine the effect of caffeine's in vitro diffusion profile. Microemulsion gel was prepared using tween 80 as a surfactant, glycerin as cosurfactant, viscolam mac 10 as a gelling agent. The preparations were evaluated by organoleptic, pH, viscosity, rheology, spreadability, globule size, and thermodynamic stability tests. In vitro diffusion tests were performed by Franz diffusion cell. The result showed that microemulsion containing 1 % of caffeine and 5% of grapeseed oil has good physical characteristics and stability with an average globule size 126 ±17 nm. Microemulsion gel system could enhance the cumulative release amount of caffeine through synthetic membrane compared with gel system. Drug release kinetics of caffeine from microemulsion gel system follows the Higuchi model.

The yoghurt consisted of low-fat milk, three bacterial strains starter, which included: L. bulgaricus ATCC 11842, L. plantarum ATCC 8014, and B. longum (1:1:1); purple sweet potato puree (Ipomoea batatas, L.) and carboxymethylcellulose sodium with the concentration of 0.6%, 1.2%, and 1.8%. Purple sweet potato fortification in yogurt can prevent hypercholesterolemic conditions because it inhibits lipid and sugar absorption in the intestine. Unfortunately, there is one shortcoming in the production of yogurt which affects the final product quality. This shortcoming is in the decrease in the air holding capacity (whey off) during the production due to the pH level within the isoelectric point of casein. This causes precipitation and phase separation. This study will add a stabilizer to the formula to overcome it. The stabilizer used is carboxymethylcellulose sodium, which is semi-synthetic water-soluble ester polymer cellulose. This study aimed to determine the optimal concentration of carboxymethylcellulose sodium and its effect on purple sweet potato yogurt's physicochemical and organoleptic properties. The product quality evaluations were on organoleptic evaluation, density, viscosity, and pH level. Centrifugation and freeze-thaw tests were also performed to evaluate product stability. The results showed that carboxymethylcellulose sodium could maintain the stability of purple sweet potato yogurt by binding the air content, increasing consistency, and smoothing the texture even though it did not affect the freezing point of the product. This study gave the best results for purple sweet potato yogurt with 1.2% carboxymethylcellulose sodium concentration.

Arabian bidara leaves (Ziziphus spina-christi, L.) are known to have strong antimicrobial activity against microorganisms that cause infection in the female genital area, namely Staphylococcus aureus bacteria and Candida albicans fungi. They contain main secondary metabolites such as flavonoids, alkaloids, and saponins. Christinin is a saponin glycoside derivative compound which consists of four types, namely christinin-A, B, C, and D. The role of computational studies in the discovery of new drugs is crucial and interesting nowadays because it is relatively cheap, effective, fast, and precise with a reliable level of accuracy. This computational study result will later be used to confirm in vitro test results which are carried out using experimental microbiological testing methods in the laboratory. This study identified, evaluated, and explored the interactions between christinin-A, B, C, and D compounds with Penicillin Binding Protein (PBP) from Staphylococcus aureus and Dihydrofolate Reductase from the fungus Candida albicans using computational study were carried out using the molecular docking. The christinin-A, B, C, and D compounds were modeled into 3D conformation using GaussView 5.0.8 and Gaussian09 software. The best conformation was selected for molecular interaction studies on Penicillin Binding Protein (PBP) from Staphylococcus aureus bacteria and Dihydrofolate Reductase from Candida albicans using MGLTools 1.5.6 software with AutoDock 4.2. The molecular interactions that occurred were further observed using the BIOVIA Discovery Studio 2020 software. Based on the molecular docking results, the christinin-B compound had the highest affinity for Penicillin Binding Protein (PBP) from Staphylococcus aureus bacteria, with a binding-free energy value of −7.67 kcal/mol. Meanwhile, the christinin-A compound has the highest affinity for Dihydrofolate Reductase from the fungus Candida albicans, with a binding-free energy value of −8.38 kcal/mol. Thus, it is predicted that christinin compounds can be chosen as the main component in feminine hygiene preparations to maintain the female genital area's health.

Diclofenac sodium is a Non-Steroidal Anti Inflammatory Drugs that if being taken orally have the side effects of peptic ulcers and undergone the first pass metabolism, and also included in the Biopharmaceutics Classification System class 2 which resulted in the low rate of dissolution. This study aims to determine the influence of particle size reduction on the dissolution rate of diclofenac sodium in the form of an FDOF dosage. The formation of diclofenac sodium nanoparticles is carried out by ionic gelation method using chitosan and sodium tripolyphosphate as a crosslinker in various ratios characterized by Particle Size Analyzer and Scanning Electron Microscopy, then it is incorporated into the form of an FDOF that were prepared by solvent casting method at a dose of 12.5 mg using variations concentration of SSG as superdisintegrant and PEG 400 as plasticizer. From the research results, diclofenac sodium nanoparticles are formed in the ratio of chitosan-sodium tripolyphosphate 6:1, have a size of 804 nm and spherical-shaped. The best FDOF dosage formula is F8 containing HPMC E5 LV 35% as the film forming agent, SSG 8% as superdisintegrant and PEG 400 10% as plasticizer. FDOF formula containing diclofenac sodium nanoparticles has a slightly bitter taste, disintegration time less than one minute, surface pH around 7 (neutral), drug content that meets the requirements of the range of determination which is 93.24 ± 0.96, the cumulative amount of drug dissolved in the 28th minute is higher by 88.45% compared to FDOF containing diclofenac sodium raw material, which is only 70.0%.

Glimepiride is often combined with metformin HCl as an oral antidiabetic in type II diabetes mellitus, which provides a complementary and synergistic effect with multiple targets for insulin secretion. Glimepiride includes class II of BCS, which solubility practically insoluble in water but high permeability, which will impact the drug's small bioavailability. In contrast, metformin HCl includes class III of BCS, which has a high solubility in water, but low permeability is absorbed approximately 50-60% in the digestive tract given orally. The co-crystallization method can be used to improve the glimepiride solubility properties and the permeability properties of metformin HCl by interrupting glimepiride with metformin HCl physically. This study aims to identify the physical interactions between glimepiride and metformin HCL using a thermal analysis of Differential Scanning Calorimetry (DSC) and then confirmed by a computational approach. Identifying the physical interactions between glimepiride and metformin HCL was carried out by plotting the melting points generated from the endothermic peaks of the DSC thermogram at various compositions versus the mole ratios of the two were further confirmed by the computational approach using PatchDock. The results of the phase diagram analysis of the binary system between glimepiride and metformin HCl show a congruent pattern, which indicates the formation of co-crystal or molecular compounds at a 1 : 1 mole ratio at 228°C. Computational approach results showed that the interaction between glimepiride and metformin HCl did not form new compounds but heterosinton formation that was stable in molecular dynamics simulations.

Glimepiride is a third generation sulphonylurea antidiabetic drug. Glimepiride is poorly water soluble drug that may cause poor dissolution and unpredicted bioavailability. Self nanoemulsifying drug delivery systems (SNEDDS) have become a popular formulation option as nanocarriers for poorly water-soluble drugs. The objective of this research was to develop SNEDDS formulation of glimepiride to improve oral dissolution and bioavailability. Glimepiride SNEDDS was formulated using oleic acid as oil phase, tween 80 as surfactant, and transcutol as co-surfactant due to their higher solubilization effect. The formulated SNEDDS were evaluated for % transmittance, dispersibility, thermodynamic stability, dissolution, globule size and morphology analysis. The results showed that the glimepiride SNEDDS was rapidly formed clear emulsion and stabile based on thermodynamic test. Transmission electron microscopy demonstrated the spherical droplets morphology in nanometer range. The globule average diameter size was 45 nm. The SNEDDS formulation significantly increase dissolution of glimepiride compared with pure drug.