Solid State Engineering of Anti gout Drugs Drug Drug Cocrystals and Coamorphous Systems

Abstract

The solid state engineering of a drug can be adapted to optimize its pharmaceutical properties. Selecting the suitable physical form of a drug provides a strategic avenue for optimizing physicochemical properties such as chemical and physical stability, solubility, dissolution rate, and bioavailability. The main objective of the present work was to develop and characterize novel solid forms of anti-gout drugs. Anti-gout drugs (febuxostat and benzbromarone) were selected as model drugs for the study. Experimental screening for drug-drug cocrystal formation of febuxostat with various NSAIDs was carried out using grinding and solvent evaporation techniques which resulted in the formation of two novel co crystal systems of febuxostat with piroxicam and meloxicam. DSC, PXRD and ATR-FTIR were used for characterization of all new systems. These novel cocrystals were evaluated for solubility, in vitro dissolution and anti-gout activity in animal model. The novel febuxostat-piroxicam cocrystals and febuxostat-meloxicam cocrystals were studied in potassium oxonate induced gout model for 8 days. The results of in vivo studies demonstrated significant decrease in uric acid level (Plt0.001) and reduction in inflammation of the joints on 8th day. In addition, these novel drug-drug cocrystals were found to demonstrate improved flow properties and compressibility as compared to plain drugs. Benzbromarone another anti-gout drug was formulated with amino acids in order to improve its solubility. Benzbromarone formed a coamorphous system with amino acid L-arginine which was characterized by DSC, PXRD and FTIR. The benzbromarone-L-arginine coamorphous system showed an improvement in solubility and intrinsic dissolution rate as compared to plain drug. All the solid forms of febuxostat and benzbromarone were found stable for 6 months at 40 and#8451; and 75% RH. In conclusion, the present research work has established the proof of concept that the solid state engineering of anti-gout molecules has resulted in improvement of their pharmaceutical