Formulation Optimization and Pharmacokinetics of Tinidazole Crystallo-Co-Agglomerates

Abstract

The purpose of this research was to obtain directly compressible agglomerates of Tinidazole using a crystallo–co–agglomeration technique and determine its in–vivo performance in rats. Crystallo–co–agglomeration is an extension of the spherical crystallization technique, which enables simultaneous crystallization and agglomeration of 2 or more drugs or crystallization of a drug and its simultaneous agglomeration with another drug or excipient. Tinidazole agglomerates were prepared from Acetone–water–DCM system containing hydroxypropyl methylcellulose (HPMC). Acetone acted as a good solvent for tinidazole, water acted as bad solvent and dichloromethane acted as bridging liquid for agglomeration. The agglomerates were characterized by powder x–ray diffraction (PXRD) which showed that there is decrease in crystallinity or partial amorphization of the drug in its agglomerated form, FTIR which showed that there is no interaction between drug and polymer and were evaluated for tabletting properties. Micromeritic and compressional properties of the agglomerates were affected by incorporated polymer. 23 factorial design was used for optimization wherein the factors were stirring speed, polymer: drug ratio and amount of bridging liquid. The responses evaluated were dissolution, MYP and Carr index. Dissolution of agglomerates increased as compared to pure drug. Also there was an increase in flow property which was indicated by Carr index of drug (40.81) and optimized batch of agglomerates (4.18). In vivo pharmacokinetic studies of tinidazole on rats demonstrated increases in Cmax and AUC of tinidazole crystallo–co–agglomerates as compared to that of standard tinidazole and marketed formulation. But there is no significant increase in Tmax may be due to same rate of release