European Journal of Molecular & Clinical Medicine

The aim of this study was to prepare and evaluate incorporating solid lipid nanoparticles (SLNs) of diclofenac sodium for systemic delivery of the active after ocular application. Diclofenac sodium loaded solid lipid nanoparticles (SLNs) have been successfully developed using a microemulsion technique. Three different formulations were prepared It was found that variation in the amount of ingredients had profound effects on the diclofenac sodium loading capacity, the mean particle size, and size distribution of charge, morphology, and drug-lipid compatibility. At optimized process conditions, diclofenac sodium loaded SLNs showed spherical particles with a mean particle size of 450 nm and 60% diclofenac sodium  incorporation efficacy was achieved. The SLNs were evaluated for in vitro drug release, ex-vivo permeation studies. The SLN sustained the drug release for 6 h in vitro. The results suggest enhancement in ocular delivery of diclofenac sodium with incorporating SLNs

Pyrazolopyrimidines and related fused heterocycles are of interest as potential bioactive molecules. The heterocyclic fusion of pyrimidine ring and pyrazole ring resulted in formation of pyrazolopyrimidines, the structural analogues of biogenic purine class, undoubtedly, has high significance in the field of pharmaceutical and biotechnological sciences with wide spectrum of biological activities and its several derivatives. Toxicity may be due to the accumulation in a specific organ/ tissue (e.g. bosentan), the co -administration of other drugs affecting ADMET (absorption, distribution, metabolism, elimination and toxicity) Cmax reaching off target IC50, or the high Cmax required for therapeutic effects. Assessing the relative drug efficacy and toxicity is important for medicinal chemists, pharmacologists, pharmacists, physicians. As multiple treatment options are available for many diseases, relative toxicity assessment is necessary. Difficulty in direct clinical trial comparisons forces network meta-analyses for estimating the relative toxicity. Therapeutic index (TI) assumes simplified linear relationships between receptor affinity, maximum unbound plasma drug concentration (Cmax) and toxicity. But high TI does not guarantee safety. For drugs metabolized by cytochrome P450 (CYP450),estimating TI based on target potencies alone is insufficient.