International Journal of Applied Pharmaceutics

ANTIBIOTICS IN INDONESIA: ACCESS, WATCH, AND RESERVE CLASSIFICATION

DIRGAHAYUNI SARI AGUSTINA AMBARITA — 2024-05-07

Objective: The objective of this study is to compare antibiotics listed in the National Essential Medicines List (NEML) and national formulary in Indonesia by determining the proportion of antibiotics in the three groups, Access, Watch, and Reserve (AWaRe), along with median data, range values, and time trends from 2013 to 2021.

Methods: We obtained the compilation of antibiotics from the NEML and national formulary in Indonesia, covering the period from 2013 to 2021. These antibiotics were evaluated according to the 2021 WHO AWaRe classification database. This analysis involved determining the proportion of antibiotics in the AwaRe groups within each healthcare facility. Median data and range values for these antibiotics were also calculated. Trends in the proportion of AWaRe antibiotics were analyzed and visualized using a line chart.

Results: The Indonesian NEML includes 20 antibiotics, categorized into two tiers of healthcare settings. Of these antibiotics, 13 were access, seven were watch, and there was neither a reserve nor a not recommended antibiotic. The Indonesian national formulary includes 42 antibiotics, categorized into three tiers of healthcare settings. Of these antibiotics, 19 were access, 22 were watch, one was not recommended, and there was no reserve antibiotic. The proportion of antibiotics during the pre-and post-establishment of the WHO AWaRe in 2017 showed significant changes in the Indonesian national formulary but not in the NEML.

Conclusion: In recent years, the proportions of antibiotics in the Indonesian NEML and national formulary have varied according to the WHO AWaRe classification.

ENHANCING NOSE- TO- BRAIN DELIVERY OF PIRIBEDIL: DEVELOPMENT OF A NANOSUSPENSION DISPERSED IN NASAL IN-SITU GELLING SYSTEM

CHEKKILLA BHARGAVI — 2024-05-07

Objective: This study focuses on improving the delivery of Piribedil, a poorly soluble drug, to the brain through the nasal route using a nanosuspension in a nasal in-situ gel.

Methods: The nanosuspension was prepared using the sonoprecipitation method. Quality-by-Design (QbD) principles were used to optimize both the formulation and process parameters. The optimal process parameters were determined as sonication time (7.09 min), sonication amplitude (83.44%), and infusion rate (2.41 mL/min) with a desirability value of 0.970.

Results: The nanosuspension exhibited an average particle size ranging from 46.7 nm to 50.1 nm, and polydispersity index values between 0.393 and 0.425. Zeta potential values ranged from -33.78 ± 1.86 mV to -35.06 ± 2.12 mV, indicating favorable stability. FTIR studies revealed molecular interactions between Piribedil and stabilizers. XRPD and DSC analyses showed the transition from a crystalline to an amorphous state in the nanosuspension. Dissolution studies demonstrated significantly accelerated dissolution for the Piribedil nanosuspension, attributed to its nanosize and improved wettability. Stability assessments confirmed the robustness of the nanosuspension.

Conclusion: This innovative approach offers potential solutions for drug solubility challenges and blood-brain barrier penetration, holding promise for effective brain-targeted treatments.

BIOSYNTHESIS, CHARACTERIZATION AND EVALUATION OF SILVER NANOPARTICLES FROM THE LEAF EXTRACT OF PREMNA INTIGRIFOLIA L. AS A POTENTIAL ANTICANCER AGENT

SPANDANA K. — 2024-05-07

Objective: In this study, plant-based silver nanoparticles were synthesized and characterized from Premna integrifolia leaf extract to test the viability towards anticancer properties.

Methods: Preliminary identification of silver nanoparticles was validated by Visual observation and confirmed for the characterization by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX) and Fourier-transform Infrared Spectroscopy (FTIR) analysis. Further synthesized nanoparticles were evaluated against non-small lung cancer cells (A549) by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay.

Results: Aqueous leaf extract of Premna intigrifolia was synthesized for silver nanoparticles and showed an average size from 35nm to 100 nm through SEM studies. EDX showed a strong signal confirming the formation of silver nanoparticles in the metallic silver region at 5Kev, and the FTIR spectrum showed changes in some peaks of the aqueous extract with functional groups. The newly synthesized silver nanoparticles showed significant anticancer properties targeting lung cancer A549 cell line against standard drug Epotoside with a 50% Inhibitory Concentration (IC50) value of 78.431 µg.

Conclusion: The results affirm that biosynthesized silver nanoparticles can be used as an alternative to chemical medicines to cure cancer.

RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CURCUMIN AND RESVERATROL IN NANO-MICELLE: DUAL DRUG DUAL FORM SIMULTANEOUS ESTIMATION

SK MOSIUR RAHAMAN — 2024-05-07

Objective: To develop a reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous estimation of conjugated form of Curcumin (CCMN) and free form of Resveratrol (RSV) in nano-micelle.

Methods: The conjugation of lipophilic CCMN and hydrophilic Chitosan (CHT) through succinyl linker produce amphipathic molecule that can self-assemble into RSV solution to form micelle. Here RSV exists in micelle core as free form and CCMN with micelle backbone as conjugated form. So it required to estimate conjugated drug and free drug simultaneously from nano-micelle. We developed a RP-HPLC method, utilized C18 column, follow flow rate of mobile phase 1.0 ml/min, which consist of acetonitrile with water (0.5% Ortho Phosphoric acid, pH 4.6) in the ratio of 1:1 for 20 min. Injection volume was 10μl and column temperature 25 ℃. Isosbestic detection of both drugs was at 254 nm.

Results: The retention time of RSV and CCMN were at 8.15 min and 11.41 min respectively, completely distinguished sharp peak of CCMN and RSV developed with resolution 7.360±0.117, wide range of linearity with correlation coefficient value (R²) of CCMN and RSV were 0.99987 and 0.99992 respectively and recovery value of CCMN and RSV were 100.041±0.22 % and 100.041±0.21 % respectively. The RSD (relative standard deviation) for accuracy, precision and robustness of the method was found to be less than 2%.

Conclusion: The develop method for simultaneous estimation of conjugated CCMN and free form of RSV in the nano-micelle formulation was consider to be accurate, precise, robust and sensitive.

OSMOTIC DRUG DELIVERY SYSTEM OF NICORANDIL: DESIGN AND EVALUATION

SRILATHA CHOUDHARY — 2024-05-07

Objective: The purpose of the current research was to design a nicorandil formulation with controlled drug release using the principles of osmotic pump technology. Nicorandil is a biopharmaceutical classification system (BCS) class 3 drug, having a shorter plasma elimination half-life and bioavailability of 75 to 80%.

Methods: The elementary osmotic pump (EOP) was prepared by coating a cellulose acetate polymer on the prepared core tablet. A 2⁴-factorial design was applied to optimize the parameters for the osmotic tablet. A surface orifice was drilled.

Results: Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) results showed that there was no interaction between drugs and excipients. A 2⁴-factorial design was applied to optimize the parameters for the elementary osmotic pump. The optimized batch was characterized for in vitro drug release studies, and the effects of pH, osmotic pressure, and agitation intensity were analyzed. All the batches showed a drug release ranging from 90.48% to 98.78% after 12 hours. There was no change in the drug release pattern at different pHs and agitation intensities. The drug release was found to decrease with the increasing osmotic pressure of the dissolution medium. The results showed that the amounts of sodium chloride and mannitol were positively affecting the drug release, while the plasticizers PEG400 and DBP were not critical. Scanning electron microscopic studies (SEM) showed the integrity and surface morphology of the coating membrane before and after dissolution. The prepared EOP was found to deliver nicorandil at zero-order for up to 12 hours.

Conclusion: Nicorandil was developed successfully as a controlled drug delivery during a 12-hour period, with variables optimized by the use of a 2⁴-factorial design.

DEVELOPMENT AND OPTIMIZATION OF A DOLUTEGRAVIR NANOSUSPENSION USING BOX BEHNKEN DESIGN

LAKSHMI DEVI GOTTEMUKKULA — 2024-05-07

Objective: This study aimed to develop and optimize a nanosuspension of Dolutegravir, an integrase inhibitor with low aqueous solubility, using the sonoprecipitation technique. The objective was to enhance the drug's solubility and oral bioavailability by preparing nanosuspension.

Methods: A box-behnken design was employed to systematically investigate the impact of stabilizer concentration, sonication amplitude, and time on the particle size and polydispersibility of the nanosuspension formulations. Various stabilizers, including Soluplus®, Poloxamer 188, Poly Vinyl Pyrrolidone (PVP) K90, Hydroxy Propyl Methyl Cellulose (HPMC), and Tween 80, were evaluated. Fourier transform infrared spectroscopy confirmed drug-polymer interactions, while differential scanning calorimetry and X-ray diffraction revealed partial amorphization. Scanning electron microscopy confirmed nanoscale particle size and morphology.

Results: The optimized formulation (NS6) with 1% Soluplus®, 65 W amplitude, and 10 min sonication exhibited nanoparticles of 75.3 nm with low polydispersity. NS6 demonstrated enhanced drug release compared to the pure drug, attributed to particle size reduction and amorphization. In vitro tests indicated acceptable stability over time and temperature.

Conclusion: The application of Box-Behnken design resulted in an optimized nanosuspension formulation capable of improving the oral bioavailability of poorly soluble Dolutegravir. The formulation exhibited favorable characteristics, including reduced particle size, amorphization, and enhanced drug release, highlighting its potential as an effective delivery system for Dolutegravir in Human Immuno Deficiency Virus (HIV) treatment.

QUANTIFICATION AND QUALITY CONTROL OF TRIPLE-DRUG COMBINATION EMPLOYED FOR GASTRIC ULCER USING STABILITY-INDICATING SELECTIVE RP-HPLC TECHNIQUE

YADLA PAVANI — 2024-05-07

Objective: A seven-day regimen consisting of vonoprazan (VNP), amoxicillin (AXC) and clarithromycin (CRC), administered twice daily, has been permitted and reimbursed by health coverage as initial therapy. No technique has been implemented yet to determine the quantities of VNP, AXC, and CRC combination. This work effectively aimed at estimating these medications (VNP, AXC, and CRC) at the same time by developing an HPLC technique that saves money and time.

Methods: The VNP, AXC, and CRC were separated in a “Waters” column (C18 nature; 250 mm sized length; 4.6 mm sized internal diameter; 5 µm sized particle; 25 °C temperature). Phosphoric acid (0.1% in water; pH 4.2) and absolute methanol (50:50, v/v) comprise the mobile phase. The drug product, Voqueznatripak, was subjected to hydrolysis, oxidation, photolysis, and thermal stressors with the intent to cause enforced degradation. The suggested "HPLC conditions" were verified in compliance with ICH guidance.

Results: The measurements had a linear range of 10–20 µg/ml for VNP and 250–750 µg/ml for AXC and CRC. The AXC, CRC, and VNP had LOQ’s 5.302 µg/ml, 5.487 µg/ml and 0.523 µg/ml, respectively. Precision measurements were<0.2% RSD and accuracy ranges were 99.40% to 101.46%. The newly devised “HPLC conditions” specificity attribute and stability-indicating quality were also validated by forced degradation tests.

Conclusion: The newly devised “HPLC conditions” for analysing AXC, CRC, and VNP in formulation dosage form and stability samples might be adapted by quality control laboratories. The devised “HPLC conditions” is qualified and consistent to reveal and detect any probable change in the drug product assessments throughout stability experiments.

DESIGN, DEVELOPMENT AND IMPROVEMENT OF AN EMULGEL CONTAINING SILVER NANOPARTICLES AND VITAMIN D-3 FOR ITS POTENTIAL TO ACCELERATE THE HEALING OF WOUND

RISHU YADAV — 2024-05-07

Objective: The aim of this research work was to prepare a topical emulgel based dosage form incorporated with vitamin D-3 and silver nanoparticles to reduce the wound healing time in any kind of wound.

Methods: Central Composite Design (CCD) was applied for the optimization of emulgel by using Design expert software. Three responses (pH, viscosity, and in vitro drug release) and two factors (Carbopol concentration and stirring duration) were chosen, and Statistical Analysis of Variance (ANOVA) revealed that all the factors were significantly affecting the responses. Silver Nanoparticles (SNPs) was prepared with Green Tea Extract (GTE) and evaluated for particle size, Poly Dispersity Index (PDI), zeta potential and Fourier Transform Infra-red (FTIR) spectroscopy and revealed that SNPs of desired range and stability have been synthesized. Here excision wound model was used to evaluate the wound healing activity of formulation in vivo.

Results: Maximum in vitro release 88.2±2.1 has shown by the optimized formulation F13, pH and viscosity were also found in optimum range i.e., 6.2±0.4 and 1672±33 respectively, followed by Korsmeyer and Peppas model. Total eight groups were designed for animal study and silver sulphadiazine was used as marketed formulation. F13 formulation was further evaluated for in vivo data, it was revealed that emulgel loaded with high dose of vitamin D-3 along with silver nanoparticles has shown 100.5±1.7% wound contraction, while marketed formulation has shown 103.7±1.1% wound contraction, which was much similar with test formulation. Cytotoxic cell study was done using assay on chicken egg, formulation has not shown any cytotoxic behaviour like haemolysis and cell damage on chick embryo’s blood vessels. Accelerated stability study of the optimized formulation was also performed to check whether the formulation was stable or not and it was revealed that optimized formulation was found stable for the period of six months.

Conclusion: It was revealed that emulgel loaded with high dose of vitamin D-3 and SNPs found suitable to accelerate wound healing and showed almost similar response in wound contraction on comparison with marketed formulation. This emulgel promised to controlled the delivery of the drug for the longer duration.

IBUPROFEN INJECTABLE MICROEMULSION PREPARATION COATED BY CHITOSAN: FORMULATION, CHARACTERIZATION, IN VITRO PERFORMANCE, ANTI-INFLAMMATION ACTIVITY, AND HEMATOLOGY ASSESSMENT

AULIA UL HAFIZAH — 2024-05-07

Objective: This study aimed to develop, characterize, and conduct stability evaluations to ensure compliance with intravenous administration for microemulsion ibuprofen injection. In addition, hematology assessment and profile of drug release kinetics were analyzed.

Methods: The formulation process commenced by introducing various chitosan concentrations into microemulsion ibuprofen injection, following a method established in a previous study. Formulation parameters studied include particle size, polydispersity index (PDI), zeta potential, kinetic of drug release, anti-inflammation activity using the 1% carrageenin induction method, and hematology assessment.

Results: The results showed that the addition of 1% chitosan solution allowed for the development of the ideal microemulsion formula, with droplet size, zeta potential, and PDI of 19.37±0.32 nm,-1.53±0.12 mV, and 0.38±0.02, respectively. Kinetics of chitosan-coated ibuprofen microemulsion (MK) were governed by the squared root of time paradigm, suggesting that drug release proceeded by diffusion and was influenced by the carrier. Compared to the other groups, the paw injected with MK indicated a strong anti-inflammatory effect and did not differ significantly from the control group (p>0.05). However, Hematology analysis showed no statistically significant variations in leukocyte and erythrocyte profiles between the treatment and control groups (p>0.05).

Conclusion: MK met the criteria as an intravenous preparation based on the characteristics and safety.

THE FORMULATION AND EVALUATION OF 6-THIOGUANINE AS A NANOSTRUCTURE LIPID CARRIER FOR THE TARGETED DELIVERY OF BREAST CANCER

ALAA A. HASHIM — 2024-05-07

Objective: The main goal was to avoid all the problems associated with usual breast cancer treatment by using 6-thioguanine as a nanostructure lipid carrier (TG-NLCS). This was accomplished by administering an effective and targeted dose of 6-thioguanine (TG) to the tumour site using a long-lasting and biodegradable delivery system.

Methods: A combination of heat homogenization and ultrasonication was used to implement the emulsification process. To obtain the optimal formulation, the prepared formulations were first assessed for particle size, Polydispersity Index (PDI), zeta potential, entrapment efficiency, and drug loading capacity. Additionally, a range of physicochemical characterization techniques were employed, including dissolution studies, melting point determination, Fourier-Transform Infrared (FTIR) spectroscopy, and Field Emission Scanning Electron Microscopy (FESEM), as well as cytotoxicity assessment of TG-NLCs in MCF-7 breast cancer cells.

Results: The selected formula, TG03, showed a zeta potential of-13.5±0.27 mV and a particle size of 149±0.55 nm. This was further examined using a FESEM. In the in vitro drug release study, the formula demonstrated better-controlled drug release for 48 h in comparison to other formulations. In addition, the significant anti-proliferation activity of TG-NLCs against the MCF-7 breast cancer cell line.

Conclusion: Nanostructured lipid carriers (NLCs) are one type of multifunctional nanoparticle that includes many combinations of lipids and medicines for various delivery routes.

SINUSOIDAL ELECTROMAGNETIC FIELD DECREASES OSTEOGENIC DIFFERENTIATION OF RAT BONE MARROW MESENCHYMAL STEM CELLS

DHIYA ALTEMEMY — 2024-05-07

Objective: The widespread use of household electrical appliances generating electric and magnetic fields was a significant focus of WHO attention because of its serious threat to human health, especially osteogenesis. This research investigated the effect of 50 Hz frequency (1 mT intensity) sinusoidal EMF (SEMF) on the osteogenic differentiation of rat bone marrow stem cells (rBMSCs) in vitro.

Methods: Experimental groups were: positive control (cells cultured in osteogenic medium supplemented with 7-10 M Dexamethasone, negative control (cells cultured in α-MEM/10% FBS, 10 mmol Beta-Glycerol-Phosphate, 15% FBS, 50 ug/ml Ascorbic Acid bi-Phosphate, 100 unit/ml Penicillin) and for the EMF group, cells exposed to SEMF (50 Hz, 1 mT, 30 min/day) for 14 and 21 d. Alizarin red staining, Alkaline phosphatase activity, and QRT-PCR were performed.

Results: The EMF group exhibited weaker positive stains for ALP and Alizarin red than the positive control group. The Runx2 and Ocn gene expression levels were significantly decreased compared to negative control at 14 and 21 d of EMF exposure, respectively. After 14 and 21 d of exposure, Runx2 and Ocn gene expression were much lower in the EMF group than in the positive control group.

Conclusion: SEMF (1 mT, 50 Hz, 30 min/day) could retarded osteogenesis and reduce the osteogenic differentiation of rBMSCs.

PREDICTION OF SULFAMETHOXAZOLE AND TRIMETHOPRIM PLASMA LEVELS FROM TABLETS AND DISSOLUTION MEDIA OF PHYSIOLOGICAL RELEVANCE

JOSE MANUEL RIOS-RODRIGUEZ — 2024-05-07

Objective: To estimate plasma concentrations-time profiles of Sulfamethoxazole (SMZ) and Trimethoprim (TMP) from fixed-dose combination formulations through in vitro data of dissolution media of physiological relevance and a convolution model.

Methods: Dissolution profiles of SMZ/TMP tablets (400/80 mg) were obtained with USP paddle apparatus at 100 rpm and 900 ml of 0.1 N HCl, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. The reference drug product and two generic formulations were tested. Drugs were quantified by a derivative method. Dissolution profiles were compared with model-dependent and independent methods. SMZ/TMP plasma levels were simulated with dissolution data and published in vivo information. Percent of prediction error (PE) for peak plasma concentration (C_max) and area under the curve from zero time to infinity (AUC_0-inf) at each condition were calculated.

Results: In all used conditions, similar dissolution profiles were found excepting for TMP at pH 1.2 (f₂<50). The in vitro release performance for reference and generic formulations was explained by the Weibull function only for SMZ at pH 6.8 and TMP at pH 4.5. Values of PE>19% for both generic formulations were found with TMP at pH 1.2.

Conclusion: Significant differences in TMP dissolution profiles of generic formulations at pH 1.2 reflect the subsequent differences found in predicted C_max and AUC_0-inf.

DEVELOPMENT, OPTIMIZATION AND IN VITRO CHARACTERIZATION OF HALOPERIDOL NANOCRYSTALS USING 32 FACTORIAL DESIGN

DAMINENI SARITHA — 2024-05-07

Objective: The main aim of the present study was to improve the dissolution rate of Haloperidol nanocrystals and thereby increase their bioavailability. Haloperidol is a typical antipsychotic drug and it is used to treat schizophrenia as well as acute mania and mixed states associated with bipolar disorder. Haloperidol falls into the Biopharmaceutics Classification System (BCS-II) class of drugs (poorly soluble aqueous and highly permeable) and has poor bioavailability.

Methods: The present study involves the preparation and optimization of Haloperidol nanocrystals by the anti-solvent precipitation method using Polaxomer407 and polyvinyl pyrrolidone K30 (PVP K30). The prepared nanocrystals were evaluated for various parameters like particle size, zeta potential, % drug content, % yield, surface morphology, drug-excipient compatibility studies (Fourier-transform infrared spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC)), and in vitro dissolution studies.

Results: Nine preparations were done and the best preparation amongst them was selected for further studies. F₇preparation containingpolaxomer407 and PVP K30 was selected as optimized preparation based on their evaluation parameters. 3² factorial design was used in the preparation. The particle size of the F₇ nanocrystals was 300.2±2.7 nm and the zeta potential-36.3±3.2 mV. The % yield was in the range of 63.62±0.3%-98.21±0.8 %. The drug content of various preparations was found to be in the range of 58.46±0.8%-93.54±0.5 %. In vitro dissolution studies showed the highest % drug release for F₇(91.54±0.03%) in 10 h.

Conclusion: F₇ preparation was found to be having acceptable characteristics and thus selected as optimized preparation.

DEVELOPMENT AND OPTIMIZATION OF SUPER SATURABLE SELF-NANO EMULSIFYING DRUG DELIVERY SYSTEM FOR DASATINIB BY DESIGN OF EXPERIMENT

C. RAJINIKANTH — 2024-05-07

Objective: In current research, Self-Nanoemulsifying Super Saturable Drug Delivery Systems S‑SNEDDS was formulated to attain superior drug dissolution and stability.

Methods: Using saturated solubility, capryol ® 90, cremophor®-EL, and transcutol HP were used to make S-SNEDDS. Its composition was optimized using the ternary phase diagram. Using the central composite design of Response Surface Methodology, dasatinib-SNEDDS developed responses for droplet size (Y1), polydispersity index (Y2), and % drug released in 15 min (Y3). Various Precipitation Inhibitors were added to optimize SNEDDS (S3) to make S-SNEDDS and evaluate.

Results: The optimum formulation was S3, with a particle size of 128 nm and zeta potential of-21 mV. Methylcellulose was shown better supersaturation than other inhibitors. The optimized formulation (F3) was more stable than ordinary SNEDDS due to its more significant zeta potential (-25 mV) and lower particle size (128 nm). Dasatinib was shown to be amorphous in S-SNEDDS using Differential Scanning Calorimetry and X-ray Powder Diffraction. F3 had a higher 90 min release rate (>99%) than pure drug dispersion (26%) and SNEDDS formulation (95%).

Conclusion: The results concluded that S-SNEDDS formulation successfully enhanced the dissolution and stability of dasatinib.

CHIRAL SWITCHING CONTROL OF PHARMACEUTICAL SUBSTANCES

OLGA V. LEVITSKAYA — 2024-05-07

Objective: The aim of this study was to demonstrate that chiral switching should be recognized as a widespread phenomenon that extends beyond the production of pure enantiomeric drugs.

Methods: To investigate the optical activity of substances from various chemical classes, enantiomers of chiral compounds (Sigma-Aldrich, USA) were chosen: valine and its racemic form (D-valine, L-valine, and racemic valine with optical purity ≥ 99%), L-ascorbic acid (content ≥ 99%), carbohydrates (D-glucose, D-galactose, L-galactose, contents ≥ 99.5%). Solutions were prepared using deuterium-depleted water (DDW–"light" water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), and heavy water (99.9% D₂O; Sigma-Aldrich). Optical activity was measured using the Atago POL-1/2 polarimeter.

Results: One of the components in the racemic medication mixture can act as an inert agent, exhibit toxicity, or undergo undesirable biotransformation mechanisms, resulting in the formation of products with unknown properties. It has been established that a change in the deuterium/protium (D/H) ratio in water leads to a change in the equilibrium and kinetic characteristics of optically active compounds across various chemical classes, such as amino acids, carboxylic acids, and carbohydrates. An inequality was observed in the absolute values of the optical rotation of the L-and D-isomers of valine and galactose, depending on the D/H isotope ratio. The impact of chiral water clusters on optical rotation accounts for the sudden shift in the specific rotation of dilute solutions (less than 0.5%) of L-ascorbic acid in water, based on the D/H ratio. The influence of the isotopic composition of water was confirmed by studying the temperature-dependent mutarotation kinetics of D-glucose and L-and D-galactose in Arrhenius coordinates.

The mutarotation process in natural high-resistivity water is characterized by an activation energy (E_a) of 40.8±1.4 kJ mol^-1, while in deuterium-depleted water, E_a = 63.6±3.5 kJ mol^-1. This results in a kinetic isotope effect for deuterium (KIED) of 1.6.

Conclusion: Methodological approaches have been developed to control chiral switching based on the isotopic composition of water in vivo and in vitro. The study of changes in the optical activity of hierarchical structures in the human body, the influence of solvent properties on the mechanisms of optical rotation, as well as the use of KIED values, can be utilized to monitor various chiral transitions in vitro and living organisms.

DEVELOPMENT AND VALIDATION OF A SIMPLE AND COST-EFFECTIVE UV SPECTROPHOTOMETRIC METHOD FOR QUANTIFYING LINEZOLID

ITI CHAUHAN — 2024-05-07

Objective: This study focuses on the development and validation of a sensitive, simple, accurate, precise and cost-effective Ultraviolet-Visible (UV) spectrophotometric method for the quantification of Linezolid, a widely used antibiotic in pharmaceutical formulations.

Methods: The analysis utilized a solvent system comprising 80% water and 20% methanol (v/v). The absorbance of standard solutions was measured and a calibration curve was constructed. Various analytical performance parameters, including linearity, range, precision, accuracy, Limit of Detection (LOD), Limit of Quantification (LOQ) and ruggedness, were determined following the International Conference on Harmonization (ICH) Q2 (R1) guidelines.

Results: The maximum absorption peak (λ_max) of Linezolid was determined to be 251 nm in the selected medium. Beer-Lambert’s law was valid in the concentration range of 0.5–9 μg/ml, with a high correlation coefficient (R²) of 0.9955. The proposed method exhibited a recovery ranging from 99.08 to 100.37% with % Relative Standard Deviation (RSD) value consistently below 2%.

Conclusion: The study findings confirm the accuracy, precision and reproducibility of the developed method. Additionally, it is characterized by its simplicity, affordability, and time efficiency. Thus, this method can be effectively employed for the quantification of Linezolid in lipid nanoparticles.

IN SILICO, PREPARATION AND IN VITRO STUDIES OF BENZYLIDENE-BASED HYDROXY BENZYL UREA DERIVATIVES AS FREE RADICAL SCAVENGERS IN PARKINSON’S DISEASE

JAGDISH CHAND — 2024-05-07

Objective: The study focuses on the benzylidene-based hydroxy benzyl urea derivative as free radical scavengers in PD.

Methods: The derivatives were designed, synthesized, and characterized using FTIR, ¹H, ¹³C-NMR, and Mass spectrometry. Further in vitro studies were performed on the SHSY-5Y cell lines. Molecular docking and molecular dynamic studies were performed at 100 ns to predict the binding affinity and stability of the ligand/protein complex.

Results: Among the nine derivatives, compounds HBU-2, and HBU-4were found to have the highest binding affinity-9.699 kcal/mol, and-9.020 kcal/mol with the amino acid interactions SER 149, PHE 157, ARG 158, SER 159, ILE 230, and ASP 231. Further, this HBU-1 to HBU-9 derivatives were produced using a synthesis route. The neurotoxicity studies were performed on the SHSY-5Y cells, where the % cell viability for the compound HBU-2, and HBU-4 was 91.22 %, and 90.42 %at a minimal concentration of 125 µg/ml with a p-value<0.011. Further, the cell counts and LDH assay for the compound HBU-2, and HBU-4 with MPP⁺treatment predicted 0.72-fold change and 0.66-fold change. The ROS % activity was also measured for compounds HBU-2 and HBU-4 in conjunction with the MPP⁺induction. In the SHSY-5Y cell line, compound HBU-2 downregulated the ROS level to 45%.

Conclusion: The synthesized compounds were found to have good free radical scavenging properties on SHSY-5Y neuroblastoma cell lines, considering these derivatives could be further assessed using appropriate PD models.

FORMULATION AND STABILITY EVALUATION OF ANTI-OBESITY NUTRACEUITCAL BLEND OF WHITE KIDNEY BEAN EXTRACT (PHASEOLUS VULGARIS L.), PROPOLIS ETHANOLIC EXTRACT AND CRPIC3

DOAA SALAH ELDIN ABDELFATTAH — 2024-05-07

Objective: This study aimed to formulate and evaluate the stability profile of an anti-obesity nutraceutical combination in different dosage forms.

Methods: Active and inactive ingredients were formulated into pharmaceutical dosage forms. The quality parameters of the dosage forms were determined, followed by accelerated stability testing (40±2 °C and 75±5% Relative Humidity (RH)) for 180 d was completed to evaluate their physical, chemical and microbiological attributes throughout the storage period.

Results: Pre-formulation parameters of the powder blend of active and inactive ingredients for each dosage form showed a satisfactory flowability with Hausner's ratio falling between 1.16 and 1.18, average angle of repose between 22.29° and 22.90° and acceptable compressibility with Carr’s index below 25%. Tablets assessments were acceptable with a mean friability value of 0.21±0.03%, hardness of 4.12±0.09 kg/cm². The average disintegration time of 5 min 10 sec for tablets and 4 min and 30 sec for capsules. The accelerated stability study revealed that tablet dosage forms are stable for longer period that can reach up to 180 d (24 mo real-time), while sachets and capsules are stable for a period of 135 d (18 mo real-time).

Conclusion: The anti-obesity blend of White Kidney Bean Extract (WKBE), Propolis Ethanolic Extract (PEE) and CrPic₃ can be successfully formulated in acceptable and convenient dosage forms that can be stable for 18-24 mo.

EFFECT OF POLYMER CONCENTRATION AND SURFACTANTS ON PHYSICAL CHARACTERISTICS, DRUG RELEASE AND ANTIOXIDANT ACTIVITY OF GLUTATHIONE-KAPPA CARRAGEENAN NANOSPHERES

YUYUN NAILUFA — 2024-05-07

Objective: Glutathione is one of the antioxidants widely used as an antiaging and skin lightener. Glutathione at a dose of 250 mg/d orally proved useful as an antiaging. At the same time, glutathione topical night cream is effective at a dose of 0.1% for the skin of Indonesian women. Glutathione is one of the antioxidants that has easily oxidized properties in storage. Research purpose to optimize the concentration of kappa carrageenan polymer and surfactan to obtain the optimal physical characteristics of nanosphere system analyzed based on size, PDI, yield, drug loading, entrapment efficiency, dissolution and antioxidant activity.

Methods: The most commonly used method of making nanospheres is ionotropic gelation because it has proven effective, easy, and easy to apply. Ionotropic gelation is depend on the tendency of polyelectrolytes to cross connect to develop hydrogel beads often called gelispheres in the existence of counter ions. Nanospheres were prepared by aerosolization ionotropic gelation technique followed by freeze-drying. This method uses carrageenan polymers of 0.5% and 1.0% with the addition of surfactant as a stabilizer. Evaluation parameters are particle size, entrapment efficiency, drug loading, drug release and antioxidant activity.

Results: The results of the nanospheres obtained were tested physically and drug activity. Nanospheres successfully formed, with size 382.67±52.24 nm, F2 325.20±4.62 nm, F3 495.39±30.61 nm, and F4 409.80±4.11 nm. The greater the polymer concentration, the greater the value of entrapment efficiency and drug content in the nanosphere. The morphology of the nanosphere is quite good, spherical, with a smooth surface. The release profile shows that glutathione release is quite good but takes a long time, namely F1 73.91±2.17%, F2 75.91±2.76%, F3 78.56±2.82%, and F4 79.56±1.34% in 480 min or 8 h. Antioxidant activity of glutathione-Kappa carrageenan nanospheres with the DPPH method showed that nanospheres have medium or medium category antioxidant activity.

Conclusion: The most optimal formula is F4 with 1% kappa-carrageenan concentration and 0.6% KCl.

A NEW RP-UPLC METHOD FOR THE SEPARATION AND SIMULTANEOUS QUANTIFICATION OF DORZOLAMIDE HCl AND TIMOLOL MALEATE

ASHA ELURU — 2024-05-07

Objective: This investigation demonstrates a stability-indicating and reliable “reverse-phase ultra-performance liquid chromatography” method to simultaneously quantify timolol maleate and dorzolamide HCl in the pharmaceutical dosage form.

Methods: Successful separation was accomplished using Phenyl column (100 mm x 2.1 mm, 1.7μm) with isocratic type of elution using mobile phase containing Acetonitrile+Ammonium Formate buffer (30:70), respectively with 0.2 ml/min flow rate. The wavelength sensor was attuned at 266 nm to quantify timolol maleate and dorzolamide HCl.

Results: Dorzolamide HCl and timolol maleate peaks were eluted with fine resolution at retention times 0.7 min and 1.5 min, respectively. In the 55.75-334.5 μg/ml and 6.25-37.5 μg/ml concentration ranges for dorzolamide HCl and timolol maleate, the calibration graphs were linear, with regression coefficients of 0.99997 and 0.99991, respectively. The suggested ultra-performance liquid chromatography approach has been shown as sensitive, precise, robust, accurate, specific and stability, indicating through the resolution of dorzolamide HCl and timolol maleate from its degradation-based compounds.

Conclusion: The established ultra-performance liquid chromatography technique was effectively extended to the evaluation of dorzolamide HCl and timolol Maleate in the pharmaceutical dosage form and the test results appeared satisfactory.

FORMULATION AND EVALUATION OF RED GINGER RHIZOME EXTRACT SOAP AS AN ANTIBACTERIAL

NOVI NURLENI — 2024-05-07

Objective: Current research work aimed to develop a formulation of red ginger into a stable soap preparation, effective as an antibacterial and safe for long-term use.

Methods: The maceration method was used to extract red ginger rhizome. In the formulation, there are variations in the concentration of the extract, where Formulation I (FI) 3%, Formulation II (FII) 5%, Formulation III (FIII) 7%, and Formulation IV (FIV) 0%. The evaluation of the preparation includes tests such as sensory evaluation, homogeneity, pH, viscosity and flow properties, density, foam height, and stability, as well as antibacterial activity using the agar diffusion method against Staphylococcus aureus ATCC 25932 and Escherichia coli ATCC 25922.

Results: The percentage of extract yield obtained was 2.38%. All three formulations of soap have shown good stability during the 28-day evaluation (significant>0.05), indicating no significant changes during storage, and the inhibitory power of Staphylococcus aureus ATCC 25923 bacteria in the three successive formulations was 9.03±0.4; 12.21±0.3; 15.26±0.4 (mm) respectively, while that of Escherichia coli ATCC 25922 was 6.01±0.6; 10.32±0.4; 12.58±0.6 (mm).

Conclusion: The evaluation results, all formulations have good stability during storage. The variation in concentration of red ginger extract will affect the inhibitory power against test bacteria. F III, with an extract content of 7% has better antibacterial activity compared to other formulations.

DEVELOPMENT OF MYCROCRYSTALLINE CELLULOSE ORIGINATE FROM SAGO (METROXYLON SAGU) STEM BARK BY HYDROLISIS METHODE USING NITRIC ACID

NUR ILLIYYIN AKIB — 2024-05-07

Objective: Microcrystalline cellulose (MCC) is an essential excipient in tablet formulation. Mostly MCC was obtained from wooden conifer stem fiber, therefore environment issues had been came up. Alternative sources for MCC which offer friendly conifer wood need to be explored. This study aimed to isolate and determine the characteristics of MCC originated from Sago (Metroxylon sago Rottb.) stem fibers as an promising alternative of MCC.

Methods: MCC was prepared through pre-hydrolysis using an acetic acid solution, alkali heating using NaOH solution, and acid hydrolysis using nitric acid 0.3 N using three variations of heating temperature, namely 90, 95 and 100 °C. The characterization carried out were pharmaceutical grade, powder properties, FTIR analysis and powder morphology by SEM.

Results: The yields obtained were 66.02; 65.53 and 65.08%, respectively. The characteristics of the MCC sample based on pharmaceutical grade quality were white to yellowish white powder, odorless, tasteless, insoluble in: ether, 96% alcohol, HCl 2N and NaOH 1N. The pH of the MCC suspension were 5.07-5.12, while moisture content were 3.67-4.17%, with loss on drying value as much as 0.37-0.4%, and ash content 1-2.17%. The value of permanganate number were 0.09-0.11, Hausner factor was between 1.05-1.25, and angle of repose were between 11.4-24.8°.

Conclusion: Based on the results, it can be concluded that Sago is potent natural resource for MCC. The resulting MCC revealed physicochemical and characteristic of MCC, which almost similar to Avicel PH 102 as standard.

DESIGN AND OPTIMIZATION OF ESCITALOPRAM OXALATE ORAL DISSOLVING FILMS BY RESPONSE SURFACE METHODOLOGY

CHENNUPATI VENU BABU — 2024-05-07

Objective: To develop and optimise the oral dissolving films of escitalopram oxalate by response surface methodology.

Methods: Oral dissolving film compositions were optimized by central composite design. The films are prepared by solvent casting method. Initially, different polymers were screened and based on the results polyvinyl alcohol was selected as polymer, propylene glycol was selected as plasticizer. Concentration of polymer and concentration of plasticizer were fixed as independent variables; tensile strength, percent elongation, elastic modulus and amount dissolved up to 5 min (%D_{5 min}) were taken as responses.

Results: The prepared films exhibited good surface characteristics. The thickness, uniformity of weight, surface pH and drug content are within acceptable range. The mechanical properties like tensile strength, folding endurance, percent elongation and elastic modulus were determined. The statistical analysis showed that polymer concentration has a positive effect on disintegration time and the plasticizer concentration has a significant effect on folding endurance. The prepared film relesases nearly 95% at the end of 5 min. The design space was used to optimize the quantities of polymer and plasticizer. The comparison of checkpoint experiment batch responses are corelating with the predicted responses.

Conclusion: Escitalopram oxalate oral dissolving films was successfully designed and optimized by response surface method. It was concluded that the prepared films exhibit good mechanical properties and maximum release within 10 min.

FORMULATION DEVELOPMENT AND IN VITRO PENETRATION TEST OF ETHOSOME OF CHROMOLAENA ODORATA LEAVES EXTRACT

SOFIA RAHMI — 2024-05-07

Objective: This study aimed to develop and assess ethosome preparation using extracts derived from the leaves of Chromolaena odorata.

Methods: The study started by obtaining Chromolaena odorata leaf extracts. Furthermore, Ethosome formulations were produced using a thermal technique. Ethosome variants were created, each with distinct compositions: Formulation F1, containing 10 ml of ethanol without the extract; Formulation F2, consisting of 0.5 grams of the extract mixed with 10 ml of ethanol; Formulation F3, combining 1 gram of the extract with 20 ml of ethanol; and Formulation F4, incorporating 1.5 grams of the extract with 30 ml of ethanol. The ethosomal systems were thoroughly characterized using various analytical techniques, such as organoleptic analysis, quantification of particle dimensions, zeta potential evaluation, pH metric analysis, transmission electron microscopy (TEM) imaging, and in vitro permeability assessment using the Franz Diffusion Cell apparatus.

Results: The findings indicated that the optimized F4 formulation showed 161.2±32.0 nm particle size measurement and a+34.33±0.58 mV zeta potential. All formula possess a pH range of 4.5-6.5, within which the skin can acclimate to preparations. It is evident from all formulations that the pH decreased after the addition of the extract at an acidic pH of 4.11. Following the 12-week storage period, the pH of all treatments exhibited a modest reduction; however, it remained within the acceptable range for skin pH. Furthermore, the F4 formula also had a higher level of penetration activity.

Conclusion: The optimized ethosomal formulations of Chromolaena odorata have promising applications in enhancing the permeability and efficacy of plant-derived therapeutic agents.

ACUTE ORAL TOXICITY OF TOFACITINIB CITRATE IN WISTAR RATS: IMPLICATIONS FOR NOVEL MOUTH DISSOLVING FORMULATIONS

MEGHANA RAYKAR — 2024-05-07

Objective: Tofacitinib citrate is a commonly used therapeutic agent for various diseases. Mouth-dissolving formulations provide potential benefits for patient compliance. This study aims to evaluate the acute oral toxicity of tofacitinib citrate in these formulations to ensure their safety and efficacy.

Methods: This study aimed to assess the acute oral toxicity of tofacitinib citrate in mouth-dissolving formulations and evaluate its effects on food and water consumption, hematological and biochemical parameters, and organ histopathology. Male and female Wistar rats were divided into four groups. The control group received distilled water, while the treated groups were orally administered tofacitinib citrate at 5 mg/kg, 100 mg/kg, and 300 mg/kg. Observations were made over 14 d, assessing general appearance, behavior, food and water consumption, and mortality. Hematological and biochemical analyses and histopathological examinations were conducted on vital organs.

Results: In acute toxicity studies, Wistar rats showed no toxicity at up to 300 mg/kg tofacitinib citrate. Compared to controls, food/water intake and hematological, biochemical, and histopathological parameters of major organs remained unchanged, indicating no systemic effects and affirming the compound's safety in mouth-dissolving formulations.

Conclusion: Tofacitinib citrate in mouth-dissolving formulations demonstrated a favorable safety profile with no acute oral toxicity. Normal consumption, unchanged parameters, and no organ abnormalities support its safety. Further investigation is required to assess chronic toxicity and long-term safety.

FORMULATION OF NANOPARTICLE CONTAINING KENIKIR LEAF ETHANOL EXTRACTS (COSMOS CAUDATUS KUNTH.) AND ANTIDIABETIC ACTIVITY IN RATS

DINA PERMATA WIJAYA — 2024-05-07

Objective: This study aimed to formulate the ethanol extract of kenikir leaf into nanoparticles. The ethanol extract of kenikir leaves loading into nanoparticles can enhanced the stability and effectiveness of antidiabetic activity.

Methods: The nanoparticles were prepared using the ionic gelation method with chitosan and variation in sodium tripolyphosphate. The nanoparticle formula was characterized by efficiency encapsulation using spectrophotometry methods and particle size, zeta potential, and polydispersity index using dynamic light scattering (DLS). An antidiabetic activity test was initiated by inducing a high-fat and fructose diet. The parameters tested were decreasing blood glucose levels in rats.

Results: The result of the characterization of the nanoparticle was the percent of efficiency encapsulation, particle size, PDI, zeta potential, and pH were carried out to get the best formula. The best formula obtained was the percent of efficiency encapsulation of 96.20±0.0278%, the particle size of 144.6±7.800 nm, zeta potential of+15.32±0.9550 mEv, PDI of 0.48±0.070, and pH of 4.255±0.0035. The decrease in blood glucose levels in the nanoparticles of kenikir leaves extract was not significantly (p>0.05) different from the positive group (metformin) compared to the kenikir leaves extract, which decreased not really significantly.

Conclusion: Nanoparticle containing kenikir leaf ethanol extract successfully prepared into nanoparticles and the potential to increase antidiabetic activity.

MOLECULAR DOCKING DYNAMICS OF SELECTED BENZYLIDENE AMINO PHENYL ACETAMIDES AS TMK INHIBITORS USING HIGH THROUGHPUT VIRTUAL SCREENING (HTVS)

KOPPULA JAYANTHI — 2024-05-07

Objective: Thymidylate kinase (TMK) plays a crucial role in bacterial DNA synthesis by catalyzing the phosphorylation of deoxythymidine monophosphate (dTMP) to form deoxythymidine diphosphate (dTDP). Consequently, this enzyme emerges as a promising target for developing novel antibacterial drugs. However, no antibiotics were reported for this target, especially active against Staphylococcus aureus thymidylate kinase.

Methods: Benzylidene acetamide-based ligands were examined for their potency using the in silico method. These novel ligand structures were built using ChemDraw software. The protein was retrieved from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) website. The molecular docking and binding free energy calculation by prime Molecular Mechanics in Generalized Bond Surface Area (MM-GBSA) was performed for selected ligands. A 100 ns molecular dynamic simulation was also performed to assess the stability of the potential ligand as TMK inhibitors.

Results: All ten molecules have shown good glide scores and hydrophobic and hydrogen hydrophobic hydrogen bonding interactions with Arg48, Arg36, and π-π stacking Phe66 in the TMK enzyme (PDB: 4HLC). Among them, N-(2-ethylphenyl)-2-(4-((4-nitrobenzylidene) amino) phenoxy) acetamide molecule had high XP-docking scores of-3.27 kcal/mol based on extra-precision data. Prime Molecular Mechanics in Generalized Bond Surface Area study (MM-GBSA) studies also showed promising binding affinities that are Δ_Bind (-65.80), Δ_Lipo (-28.55), and Δ_VdW (-55.10). Phe66 amino acid residue maintained continuous connections with the ligand during MD simulation. This ligand showed promising binding affinity with the SaTMK target.

Conclusion: The N-(2-ethylphenyl)-2-(4-((4-nitrobenzylidene) amino) phenoxy) acetamide ligand at the position of the benzene ring displayed nitrogen and oxygen group, thus indicating good potential activity as the inhibitor of TMK to treat antibacterial agents.

STUDY OF THE INHIBITORY EFFECTS OF VITAMIN E DERIVATIVES ON MITOCHONDRIAL COMPLEX II SUBUNIT USING MOLECULAR DOCKING

IRMA RATNA KARTIKA — 2024-05-07

Objective: The goal of this study was to create vitamin E derivatives and explore their potential anticancer properties using a computational approach.

Methods: The Steglich method was used for the synthesis of the vitamin E-fatty acid (pentanoic acid, heptanoic acid, and octanoic acid) derivatives, with N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as the catalysts. The structure of the synthesized products was determined by ultraviolet-visible (UV-Vis) spectroscopy, fourier transform infrared (FTIR) spectroscopy, and liquid chromatography-mass spectrometry (LC-MS). Molecular docking was carried out on the succinate dehydrogenase (SDH) enzyme using AutoDockTools.

Results: α–Tocopherol pentanoate (α–TP), α–tocopherol heptanoate (α–TH), and α–tocopherol octanoate (α–TO) were the three vitamin E derivatives synthesized in this study. Based on the results of molecular docking, the novel compounds (α–TP, α–TH, and α–TO) generated bond energies of-10.57,-9.61, and-9.20 kcal/mol, respectively.

Conclusion: All newly synthesized compounds exhibited lower binding affinity values than α–tocopherol (α–T). This confirms that these compounds might not provide greater advantages than α-tocopherol in terms of inhibitory effects on mitochondrial complex II (CII).

UTILIZATION RED DRAGON FRUIT PEEL (HYLOCEREUS POLYRHIZUS) ETHANOL EXTRACT IN ORAL THIN FILM STRIP AS A MOUTH FRESHENER

NABILA APRILIANI — 2024-05-07

Objective: The aim of this study was to formulate an oral thin film strip (OTFS) contained the red dragon fruit peel (RDFP) ethanol extract (Hylocereus polyrhizus) and evaluate the characteristic, stability and antibacterial activity against Streptococcus mutans (S. mutans).

Methods: The film was made using the solvent casting method by adding a variety of concentration ethanol extract of red dragon fruit peel (5%, 10%, and 15%). The films were evaluated in organoleptic test, weight, thickness, pH, disintegration time, folding endurance, stability test and antibacterial activity.

Results: The results showed that the film provided a distinctive color, aroma, and taste of the extract. The result of film evaluation had weight between 0.07-0.21 g, thickness between 0.10-0.20 mm, pH between 5.70-5.99, disintegration time between 34.99-49.13 s, and folding endurance between 321.00-812.83 times. The films were stable for 2 mo at a variety storage temperature (4±2 ℃, 28±2 ℃, and 40±2 ℃). The films showed antibacterial activity for 5%, 10% and 15% with the diameter of inhibition 8.5 mm, 10.8 mm, and 12.9 mm, respectively.

Conclusion: Ethanol extract of RDFP can be utilized as a mouth freshener film that is stable for 2 mo and has antibacterial activity against S. mutans.

DESIGN FOR THE COLON CANCER INHIBITORS TARGETING THYMIDYLATE KINASE BY USING INSILICO STUDIES

MOHD ABDUL BAQI — 2024-05-07

Objective: Thymidylate Kinase (TMK) plays a crucial role in bacterial DNA synthesis by catalyzing the phosphorylation of Deoxythymidine Monophosphate (dTMP) to form Deoxythymidine Diphosphate (dTDP). Consequently, this enzyme emerges as a promising target for developing novel anti-cancer drugs. However, no anti-cancer drugs have been reported for this target until now.

Methods: Ligands obtained from Benzylidene derivatives were examined for their potency by using molecular docking by glide module, Qikprop screening of Absorption, Distribution, Metabolism, and Excretion (ADME) study, and prime Molecular Mechanics in Generalized Bond Surface Area study (MM-GBSA) by binding free energy. Hereafter, a Molecular Dynamic (MD) simulation was performed at 100 ns to assess the stability of the potential ligand as a Human TMK (HaTMK) inhibitor.

Results: These ten molecules showed good binding affinity and hydrogen and hydrophobic bond interactions with Arg150, Phe42, and Phe72 in the HaTMK enzyme (PDB id: 1E2D). Among them, trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol molecule had a high XP-docking score of (−7.87 kcal/mol), based on extra-precision data. Prime MM-GBSA studies also showed promising binding affinities i.e., ΔBind (-34.59 kcal/mol), ΔLipo (-13.92 kcal/mol), and ΔVdW (-34.42 kcal/mol). Arg76 and Phe72 residues maintained constant interactions with the ligand during Molecular Dynamics (MD) simulation. This ligand showed a potential binding affinity for the TMK target.

Conclusion: The trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol ligand has active sites, namely benzene ring, benzylidene, and oxygen group, which actively participate in interaction with the protein of HaTMK, thus indicating good potential activity as the inhibitor of HaTMK to treat colon cancer.

QUANTITATIVE DETERMINATION OF SOME NON-STEROIDAL ANTI-INFLAMMATORY DRUGSAND THEIR ACID DISSOCIATION CONSTANTS BY DIRECT POTENTIOMETRY

VANIA MASLARSKA — 2024-05-07

Objective: A potentiometric titration method was applied to determine non-steroidal anti-inflammatory drugs. The quantitative analysis and the treatment of the primary data are based on a nonlinear regression procedure using commercial software. A general formula valid for every type of acid-base titration, derived before is used as a direct input.

Methods: Potentiometric titration of ibuprofen, flurbiprofen, and ketoprofen with sodium hydroxide solution (0.1 mol/l). The solutions of ibuprofen, flurbiprofen, and ketoprofen were prepared in solvent CH₃OH: H₂O (40:60%). The determination was carried out using a 713 Metrohm pH meter, equipped with Metrohm combined electrode ref. 6.0228.000 Pt1000 with temperature sensor and auto burette. The analysis was performed at ionic strength (I=0.2 mol/l KCl) and t = 25±0.2 °C.

Results: The discussed substances were analyzed using potentiometric titration with a standard sodium hydroxide solution (0.1 mol/l). The experimental data V, ml/E, mV and the conditions of these titrations were used as input in the Data Fit program fixing the following parameters Vo =100.0 ml; Ct (NaOH) = 0.1000 mol/l; S = 59.16 mV (corresponding to 25 °C theoretical value) and Kw = 1.2 10^-14 (ionic strength 0.2 mol/l). The analytical results for ibuprofen, flurbiprofen and ketoprofen were determined with good accuracy (error+0.4 % foribuprofen+0.2 % for flurbiprofen and+0.2 % for ketoprofen) and precision (1 % for the three). The quantity and acid-base constants of ibuprofen, flurbiprofen, and ketoprofen were determined alone and in tablets. The validation of the method showed very good accuracy and precision.

Conclusion: The present approach can be successfully used in routine analysis of the study drugs in quality control laboratories.

IDENTIFICATION, SEPARATION, AND CHARACTERIZATION OF DEGRADATION PRODUCTS OF TRIAMCINOLONE HEXACETONIDE USING LC AND LC-MS/MS

BHAVNA SUNIL MAHAJAN — 2024-05-07

Objective: The study aimed to separate the forced degradation products of Triamcinolone hexacetonide using HPLC and characterize the degradation product by LC-MS/MS fragmentation pattern.

Methods: Triamcinolone hexacetonide (THA) and its primary degradation products were identified using a liquid chromatography-mass spectrometry/Mass spectrometry (LC-MS/MS) approach. The degradation study was based on in-depth stress testing with acid, base, peroxide, heat, and light. A Zorbax SB C18 column and a greener mobile phase composed of methanol and 10 mmol ammonium acetate buffer in water at pH 3 were employed to accomplish separation and quantitation at a flow rate of 0.7 ml/min in an isocratic mode with a 239 nm detection wavelength.

Results: A major degradation product of the drug was obtained in acidic and alkaline stress conditions. The drug was found to be stable for all other stress conditions. The LC-MS/MS analysis results of the active pharmaceutical ingredient and resulting product after degradation were interpreted to identify the novel degradation product and fragments. The developed method was validated as per International Council for Harmonization (ICH) guidelines. The square root of the correlation coefficients, which indicated linearity for THA in 50 to 150 % of the workload, was 0.99. Method Precision assay was performed on six different preparations, percentage relative standard deviation (% RSD) of assay value is 0.17 % and system precision is 0.30 %. In accuracy, overall % RSD of 50 %, 100 %, and 150 % in triplicate is 0.95.

Conclusion: It is concluded that the drug is stable to all other stress conditions except for acidic and alkaline stress conditions and generates a novel degradation product. The developed LC (Liquid chromatography) method separates and identifies the degradation product.

DEVELOPMENT AND OPTIMIZATION OF RABEPRAZOLE CHRONO-MODULATED DRUG DELIVERY SYSTEMS

PHANEENDRA KURAPATI — 2024-05-07

Objective: Development and optimization of chrono-modulated pulsatile drug delivery systems (CPDDS) loaded with Rabeprazole for treating nocturnal acid breakthrough in ulcer patients was set as the major objective of this work.

Methods: CPDDS were developed to provide drug release as two pulses with predetermined gap. Separate microparticles for delayed instant release (DIR) and delayed extended-release (DER) were formulated. Through the optimization of several formulation and process parameters, ER microparticles were created as matrix microspheres. Central composite design was used to understand how the factors affected the responses. The optimized ER microspheres and plain drug were separately subjected to enteric coating to obtain DER and DIR portion microparticles, respectively.

Results: With the exception of stirring speed's impact on drug release, every other factor was found to have a significant influence (p<0.05) on every response. The mechanism underlying the Rabeprazole's delayed prolonged release was explained by the SEM images. The microspheres made with Eudragit RSPO at 0.72 g and polyethylene oxide at 0.5 g for 1 g of Rabeprazole at 400 rpm were shown to be the optimal formulation based on the graphical optimization results. After being coated with a terminal enteric coating, this formulation showed delayed release for a duration of 6 h.

Conclusion: After oral administration of equal doses of DIR microcapsules along with the optimized DER microspheres could release Rabeprazole effectively as two different pulses at the desired time intervals.

PREPARATION AND EVALUATION OF LAFUTIDINE NANOEMULSION AS ORAL DELIVERY SYSTEM

KARRAR T. KHUDHAIR ALBO HAMRAH — 2024-05-07

Objective: Lafutidine is a histamine (H2) receptor antagonist utilized for the treatment of gastric ulcer. Its oral bioavailability is low due to poor water solubility and an extensive first-pass hepatic. So, the present work aims to formulate and characterize of an oil in water (o/w) nanoemulsion of lafutidine as oral liquid dosage form and this could enhance drug solubility and improve its bioavailability.

Methods: The pseudo-ternary phase diagrams were constructed via titration method. The diagram plots derived from oil, various ratios of surfactant and co-surfactant (S mix), and double distilled water. The selected optimized lafutidine nanoemulsions formula was determined via a variety of investigational studies like particle size, polydispersity index (PDI), zeta potential, pH, drug content and an in vitro drug release.

Results: Characterization studies revealed that the optimum formula of nanoemulsions was (NE5), which consist of 0.2% of lafutidine, 30 % of surfactant and co-surfactant (S mix) (3:1), which mean (22.5%of tween 20:7.5% of polyethylene glycol 200 (PEG 200), 10% of peppermint oil and 59.4% of double distilled water. The optimized formula exhibited droplets size (62.56-96.2 nm), PDI (0.11), good pH value (7.1), zeta potential (-32.2 mV), high drug content (99.2%), in vitro release of lafutidine was significantly higher (P<0.05) for NE5. Scanning probe microscopy (SPM) revealed that the droplets size of NE5 was in nano-scale.

Conclusion: It is possible to conclude that the optimized formula (NE5) was promised formula of nanoemulsion for increasing the orally delivered lafutidine bioavailability.

PARTITIONING BASED PHYSICOCHEMICAL MODELS FOR ASSESSING INTESTINAL PERMEABILITY AND ABSORPTION OF DRUGS

AHMED ELGENDY — 2024-05-07

Oral administration of drugs is highly preferred for almost all human beings than any other route of drug delivery except during some health challenges. Therefore, permeability assessment of drugs across intestinal membrane is essential in the early stages of drug discovery for time and cost reasons. Animals, including humans, have been used for decades as in vivo models for determining intestinal drug permeability and absorption. However, in vivo models are very invasive, time-consuming, and not cost-effective methods. Numerous in vitro models have been used to screen drug permeability and absorption through intestinal membranes. In this article partitioning based physicochemical models that can predict a compound/drug permeability potential across intestinal membrane will be elaborated upon.

ANALYTICAL TECHNIQUES FOR DETERMINATION OF MIRABEGRON FROM BULK, PHARMACEUTICAL FORMULATION, AND BIOLOGICAL MATRICES: A CRITICAL REVIEW

SANJAY DINKAR SAWANT — 2024-05-07

Mirabegron is a beta-3 adrenergic receptor agonist and is specified for the treatment of overactive Bladder. This review covers analytical methods aimed at the identification and quantification of mirabegron in bulk, commercial dosage forms, and Biological fluids. Using various techniques such as UV-spectroscopy, spectro-fluorimetry, planer chromatography, High Performance-Thin Layer Chromatography (HPTLC), HPLC, High-Performance Liquid Chromatography-MS/MS (HPLC-MS/MS), Ultra-Pressure Liquid Chromatography-MS/MS (UPLC-MS/MS), and capillary electrophoresis. HPLC is the most used analytical technique for the identification and quantification of mirabegron in bulk and commercial dosage forms.

AUTOMATION IN ANALYTICAL CHEMISTRY: THE ROLE OF AI IN CHROMATOGRAPHY

DIVEKAR KALPANA — 2024-05-07

Artificial Intelligence (AI) has facilitated significant breakthroughs in drug discovery, the design of materials, and organic synthesis. The advancements in the latter group are especially remarkable due to the abilities of the latest computational methods (molecular design algorithms) that enable the exploration of extensive chemical spaces and enhance research in fields such as predicting molecule properties, designing molecules, retrosynthesis, predicting reaction conditions, and predicting reaction outcomes. A literary review was conducted following PRISMA guidelines. This study aimed to review existing data on the application of AI in separation chromatography. The evolution and utilization of AI in the pharmaceutical industry and its future aspects were articulated in this study. The utilization of AI can completely transform the field of chromatography analysis by facilitating expedited, more precise, and more effective data processing. By automating chromatography analysis, AI can enhance efficiency and minimize the potential for human mistakes. This advancement enables scientists to dedicate their efforts towards addressing intricate and demanding analytical issues. With the evolution of technology and the increasing adoption, we can anticipate more progress in chromatography analysis and analytical chemistry.

AN UPDATED REVIEW OF STEALTH LIPOSOMES AND ITS ABILITY TO EVADE THE IMMUNE SYSTEM: A NEW FRONTIER IN CANCER CHEMOTHERAPY

DURGARAMANI SIVADASAN — 2024-05-07

Liposomes have been the delivery of choice for the cancer targeting therapy for the last few decades. Since the 1990s, the development of sterically stabilized (stealth) liposomes has garnered interest for their long circulating half-life. PEGylated (Polyethylene Glycol) liposomes are most extensively studied for delivering cancer therapeutics in a sustained manner. Stealth liposomes are having a less intrinsic toxicity with higher efficacy in cancer treatment. There are numerous clinical trials on the liposomes in tackling cancer is evident for the better outcome of the delivery system. Stealth liposomes are extensively studied for their improved circulation time and better pharmacokinetic profile in cancer treatment. The steric hindrance of the stealth liposomes bypasses the reticuloendothelial system clearance. Further the ligands conjugation in the surface of the liposomes able to achieve better target to the cancer cells. The vascularization nature of the cancerous cells is readily making the liposomal delivery of the cancer drugs accumulate in the cancerous cells rather than healthy cells. There is an utmost need to understand the possible mechanism of stealth liposomes and the basic science behind the development of liposomal delivery system in advancing the cancer treatment with less toxicity. The present review addresses the various modalities of the liposomal development, liposome characterization, mechanism of PEGylated liposomes, the advancements and results of the liposomes in the treatment of various diseases, and the clinical trials and regulatory considerations of liposomal drug delivery system.

THE APPLICATION OF BIOANALYTICAL METHOD OF TAMOXIFEN AND ITS ACTIVE METABOLITES FOR THERAPEUTIC DRUG MONITORING IN BREAST CANCER PATIENTS: A REVIEW

MUHAMMAD IKHSAN — 2024-05-07

Breast cancer is the most common cancer around the world and in Indonesia. The most widely used agent for breast cancer treatment is tamoxifen, with a fixed dose of 20 mg per day. Tamoxifen is metabolized by cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) to endoxifen and 4-hydroxytamoxifen, which have 30-to 100-fold more potent antiestrogenic activity than tamoxifen. High variations of CYP3A4 and CYP2D6 genes can lead to interpatient variability in its metabolites concentration. The dose can be increased to 40 or 60 mg per day based on individual needs. Therapeutic drug monitoring (TDM) is required to measure the concentration of tamoxifen and its metabolites to decide the individualized dose. The measurement of drug levels should use a sensitive, selective, accurate, precise, and reliable bioanalytical method. Various bioanalytical methods have been developed in several matrices: urine, scalp hair, serum, plasma, dried blood spot (DBS), and volumetric absorptive microsampling (VAMS) samples, with different sample preparations, and frequently using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The bioanalytical method of tamoxifen and its metabolites in the DBS sample was more suitable in the TDM application due to the low invasive sampling technique, more stable sample, and rapid sample preparation. Therefore, it is more time-and cost-efficient than the other methods.

A REVIEW OF NANOPARTICLE INNOVATIONS IN CANCER THERAPY: IMPLICATIONS, TARGETING MECHANISMS AND CLINICAL PROSPECTS

LOKESHVAR R. — 2024-05-07

The main reason for morbidity and death globally is cancer, which has a complex pathophysiology. There are several traditional treatments for cancer, including chemotherapy, radiation therapy, targeted therapies, and immunotherapies. Multiple drug resistance, cytotoxicity, and lack of specificity pose significant challenges to cancer treatments. Molecular diagnostics and cancer treatment have been transformed by nanotechnology. For cancer treatment, nanoparticles (1–100 nm) are ideal because they are biocompatible, have low toxicity, excellent stability, high permeability, are precise and stable, and can deliver clear and accurate results. There are several main categories of nanoparticles. When it comes to the delivery of nanoparticle drugs, tumour characteristics and the tumour environment are considered. As well as providing advantages over conventional cancer treatments, nanoparticles prevent multidrug resistance, further overcoming their limitations. As new mechanisms are unravelled in studying multidrug resistance, nanoparticles are becoming more critical. Nano formulations have gained a new perspective on cancer treatment due to their many therapeutic applications. The number of approved nanodrugs has not increased significantly despite most research being conducted in vivo and in vitro. A review of nanoparticle oncological implications, targeting mechanisms, and approved nanotherapeutics is presented here. A current perspective on clinical translation is also provided, highlighting its advantages and challenges.

REVITALIZING THERAPEUTICS: DRUG REPURPOSING AS A COST-EFFECTIVE STRATEGY FOR DRUG DEVELOPMENT

SHIVANI MAKHIJANI — 2024-05-07

The process of developing new drugs is known for being drawn-out, expensive, risky, and having a high attrition rate. Drug repurposing has grown in favor recently as a practical way to speed up the development of new medicines while reducing the costs and time constraints associated with traditional drug research. The description of this study's pharmacological repurposing highlights its promise as a practical method to fill gaps in the market and revitalize treatment options. This review provides a full analysis of the ground-breaking tactic of repurposing medications, supported by numerous cases that demonstrate its revolutionary potential. We examine instances of repurposed drugs, such as thalidomide, sildenafil, and metformin, that have performed astoundingly well in a range of therapeutic settings despite being used outside of their original scope.

Overall, the paper's main goal-to study pharmacological repurposing as a potentially successful strategy for revitalizing treatments-is, succinctly summarized in this abstract. It highlights the potential benefits of this approach and how it might be used in the pharmaceutical industry's ongoing quest for more inexpensive and effective medicine development.

BIOLOGICAL REACTIONS OF MACROPHAGES TO METAL OXIDE NANOPARTICLES

MOHAMMED ZORAH — 2024-05-07

In our daily lives, nanomaterials are utilized extensively in paints, textiles, food goods, cosmetics, and medicine. Several investigations aim to deter investigations of the physiological effects in various cell types. The innate immune system's macrophages regulate a wide range of biological functions. Depending on the stimulus, macrophages can be activated toward pro- or anti-inflammatory (M1) phenotypes; however, polarization may change in conditions including cancer, autoimmune illnesses, and bacterial and viral infections. Metal oxide nanoparticles have recently gained significant interest due to their diverse range of unique features with applications in research and industry. The production and usage of nanomaterials will rise significantly as the nanotechnology business grows. As a result, testing the consequences of nanomaterial exposure in biological systems is critical. A comparative analysis is conducted on the toxicities of several metal oxide nanoparticles. The significance of biogenically generated metal oxide nanoparticles has been growing in recent years. However, more research is needed to thoroughly characterize the potential toxicity of these nanoparticles to ensure nanosafety and consider environmental views. To that end, nanotoxicology seeks to assess the toxicity of nanomaterials to physicochemical factors such as size and form. In this review, we focus on the biological reactions of macrophages to metal oxide nanoparticles. Because macrophages are the first cells to engage with nanoparticles when they enter the body, they can absorb them through various processes.

COMPLEX GENERICS AS A TREND OF MODERN PHARMACEUTICAL DEVELOPMENT

DEMINA N. B. — 2024-05-07

In the perspective of the pharmaceutical industry development, manufacturers expand their product portfolios by updating generic drugs. Complex Generics (CG) or Nonbiological Generic Drugs (NBGD) contain known pharmaceutical substances are out of patent protection and are made by using new technologies, excipients, nanocarriers, dosage form modernization, etc. These drugs are developed in the patients’ interests to improve their life quality and increase drugs’ efficacy and safety.

The article discusses the categories and characteristics of CG, shows examples available on the pharmaceutical market, API and dosage forms. This article discusses approaches to quality control that pose challenges for developers and regulators. The fundamental importance of the innovative drugs manufacturing process and the ingredients standardization in the dosage forms formulations to create the standard product are indicated. First, a comprehensive control of polymers is required as an important tool to make the necessary pharmacokinetics. The influence degree on the API release and the effectiveness of dosage form (DF) depends on the polymer’s physicochemical characteristics. In this regard, it is important to create databases of these excipients accessible to developers containing information about properties, use, dosages and safety.

In view of the complexity structure and manufacturing processes of the NBGD and insufficiency of pharmacopeial requirements for standard approaches for resolving issues of comparability and bioequivalence the current regulatory documents should be expanded and revise for a correct quality assessment. There is a need to create new scientific and regulatory roadmaps for the development and approval of complex generic drugs.