Search

The present study was aimed to develop the Glimepiride (GLM) loaded nanosuspension by different methods for increasing the solubility of GLM. Twelve formulations were prepared by combination method (FG), which included antisolvent precipitation method followed by sonication (Method 1) selecting drug and polymer in ratio of 1:10, 1:20 and 1:30. Further 6 formulations were prepared by nanoprecipitation method (Fg) (Method 2) selecting drug and polymer in ratio of 1:10, 1:20 by using different polymers like polyvinyl pyrolidone (PVP K30), and poly(ethylene glycol) (PEG) such as PEG 6000 and PEG 400. The GLM nanosuspensions prepared by different techniques were evaluated by optical microscopy, percent entrapment efficiency (%EE), particle size analysis, zeta potential, transmission electron microscopy (TEM) and in vitro dissolution. FG1 formulation was found to be better formulation showing 82.04% EE, 129–180 nm particle size range, 30.16 mV zeta potential, 0.253 polydispersity index (PDI) and 86.76% drug release as compared to Fgii formulation having %EE, average particle size, zeta potential, PDI value and drug release as 80.03%, 72–383 nm, -22.19 mV, 0.358 and 74.77%, respectively. On the basis of results obtained from different studies, it can be concluded that GLM nanosuspension prepared by combination technique (FG) shows good solubility and dissolution than those prepared by nanoprecipitation technique (Fg), hence the combination technique is found to be a preferred technique to prepare GLM nanosuspension over nanoprecipitation technique.

Inspired by the reported antiviral activity of pyrimidines and triazolopyrimidines, two series of 2-anilinopyrimidines (5a-e) and 1-aryl-[1,2,4]triazolo[4,3-a]pyrimidines (14a-k) were designed and synthesized as potential antiviral agents. X-ray crystallographic study of compounds (14d) and (14k) confirmed the structure of the desired isomer and revealed the coplanarity of the fused [1,2,4]triazolo[4,3-a]pyrimidine rings with the aryl side group. DFT studies revealed insights into the mechanism of the micro-reversible cyclisation step using DFT [B3LYP-D3(BJ)/6-31++G(d,p)]. The pharmacokinetic properties and calculation of drug likeness scores (DLS) of (5a-e) and (14a-k) suggested good traditional drug-like properties and led to the synthesis of derivatives (14a-k) which were evaluated for their anti-viral activity with the most potent derivatives subjected to cytotoxicity screening. Compounds (14a), (14c), (14e), (14f) and (14k) showed moderate to strong antiviral activity with EC50 values 38 - 186 μM. Compound (14e) (DLS = 0.29) showed the best anti-CHIKV activity (EC50 = 38 μM) and lowest cytotoxicity (CC50 > 300 μg/ml) against against breast cancer cell lines, MCF-7 and MD-AMB-231 and normal cell line EA.hy926. Simplification of [1,2,4]triazolo[4,3-a]pyrimidine ring, led to series (5a-e) (DLS = 0.03 - 0.77). Derivatives (5a-d) showed fair anti-CHIKV activity (EC50 > 200 μM), while (5e) emerged as the most active antiviral agent, however the most cytotoxic.