Alzheimer’s disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer’s properties. Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet’s test, p < 0.05 was considered to indicate the significance. The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Objectives: This study aimed at the methodical design and validation of a Reversed-Phase High-Performance Liquid Chromatographic method (RP-HPLC) for the estimation of Levosulpiride in bulk form using analytical quality by design approach. Methods: Using custom design, the Critical Method Parameters were methodically optimized. Peak area, retention time, and peak tailing were assessed for flow rate, buffer, and column length as the influencing elements for Critical Analytical Attributes and using an Agilent C8 column in isocratic elution mode with mobile phase NaH2PO4 buffer and methanol (50:50% v/v) and flow rate at 1ml/min. Findings: Chromatographic separation was accomplished on the Agilent C8 (150×4.6 mm, 5m) column. The optimized and predicted data from JMP PRO 14 software consisted of mobile phase NaH2PO4(50%): Methanol (50%), pumped at a flow rate of 1 ml/min which gave the higher desirability function of 77%. LOD and LOQ values were 0.06 g/ml and 0.20 g/ml respectively and models were found to be significant (p < 0.05). The validation parameter findings were within the permitted range. Forcefully testing the drug\'s stability under various stress situations revealed considerable degradation in the presence of heat. Novelty: The decrease in the retention and run time shows that the method is simple, accurate, precise and economical for the estimation of Levosulpiride that can be adopted in regular quality control tests in industries. Keywords: Analytical quality by design, Custom design, Desirability function, Levosulpiride, Reversed Phase Liquid Chromatography

The use of analytical quality by design (AQbD) process in the optimization of the high-performance liquid chromatography (RP-HPLC) method is a novel tool. The major stages of AQbD such as Risk assessment, Designing of Experiments (DOE) and Development of Method Operable Design Region (MODR) methodology are explained in detail. Factors like flow rate, column length and buffer and responses like retention time, tailing, peak area were selected to create a custom experiment design that was utilised for Epalrestat method analysis and optimisation. The optimized HPLC condition was found as NaH2PO4: Methanol (10: 90%v/v), flow rate (1.1ml/min), and UV wave length (240nm). It gives the retention time of 2.877 min with the linearity range of 50–150 μg/ml with a high regression value (r 2 = 1), and %recovery was found to be 100%. Sensitivity evaluation revealed limit of detection and limit of quantification were found to be 0.082 µg/ml and 0.2µg/ml respectively. The method was found to be precise and accurate with low % RSD of 0.2%, degradation studies were carried as per ICH Q2R1. Prediction profiler and contour plots by custom design which also confirms the robustness of the method.

Background Regulatory organizations have acknowledged the need for systematic rules for understanding development as a result of the large increase in concerns and criticism regarding the quality and pharmaceutical products. Bilastine is a second generation antihistamine medication. Generally, it is used for treatment of allergic rhino conjunctivitis and urticaria (hives). Objectives The current study outlines the methodical design and validation of a reversed-phase high-performance liquid chromatographic method for the estimation of Bilastine in bulk drugs using AQbD approach. Materials and Methods Using Box Behnken design, the critical method parameters were methodically optimized. Risk estimation matrix was performed and Critical Analytical Attributes, Critical Method Attributes were correlated to identify risk factors of method development. A reverse phase column in isocratic elution mode with mobile phase NaH2PO4 buffer and methanol of different ratio and flow rate 1 mL/min was set for RP-HPLC method development. Results Chromatographic separation was accomplished on INTERSIL C8 column. The optimized and predicted data from JMP PRO 14 software consist of mobile phase 0.1N NaH2PO4 (60%): Methanol (40%), pumped at a flow rate of 1 mL/min gave the higher desirability function of 77%. LOD and LOQ are, respectively, 0.005 mcg/mL and 0.016 mcg/ mL. The Rt of Bilastine was discovered to be 1.894 min. The created method was approved and validated in accordance with ICH Q2 (R1) recommendations. Conclusion The chosen models were determined to be significant with p <0.05. The validation parameter findings were within the permitted range. Forcefully testing the drug’s stability under various stress situations revealed considerable degradation in the presence of heat.

Hypertension affects a significant fraction of the global population and is widespread global health concern. Medical professionals frequently prescribe Calcium channel blockers as primary treatment for hypertension, due to its demonstrated efficacy and 1,4-dihydropyridine and it’s derivatives which are currently in use. The objective is to study antihypertensive effect of various analogues of 1,4-dihydropyridine derivatives with in-silico method of evaluation, synthesis and characterization. Ten derivatives were designed and docked on L-type calcium channel protein (PDB ID- 3LV3) using Autodock 1.5.7 and Biovia Discovery studio visualizer. The 5 derivatives of best binding energy were synthesized using Hantzsch method followed by characterization using IR, 1H NMR and MASS and assessments of antihypertensive activity pharmacologically by tail-cuff method using Nifedipine as standard drug. 1,4-dihydropyridine derivatives (DHP-01 to DHP-05) were synthesized and characterized. Nevertheless, a significant difference in lowering blood pressure was observed after comparing with standard nifedipine. The synthesized derivative DHP-02 was found to be effective as antihypertensive agent. Newly synthesized 1,4-dihydropyridine derivatives can be further studied for antihypertensive activity.