Improved processability of ethambutol hydrochloride by spherical agglomeration

Abstract

Ethambutol hydrochloride (ETB), high dose anti-tubercular drug exhibits poor micromeritics and compressibility. The current study aimed to enhance flow, compressibility and packing characteristics, thereby improving processability of ETB by spherical agglomeration. Quasi emulsion solvent diffusion method was used for agglomeration process in which saturated aqueous ETB solution was prepared and the crystallization was carried out subsequently at different ratios of acetone and ethyl acetate which act as anti-solvent. Further the process was optimised statistically using 32 factorial design keeping ‘speed of stirring’ and ‘ratio acetone and ethyl acetate’ as independent variables and particle size as dependent variable. Optimised batch of ethambutol hydrochloride spherical agglomerates (ETB-SA) was characterised for sieve analysis, solid state characteristics and Kawakita analysis. The uniformity of ETB-SA was observed with SEM while XRPD studies revealed reduction in crystallinity for ETB-SA. DSC and FTIR indicated no polymeric or chemical alteration during crystallization process. The flow properties of ETB-SA were found superior and its Kawakita parameters indicated improved packability and flowability compared to ETB. ETB has high solubility in water therefore was no significant difference was observed in in vitro dissolution of ETB and ETB-SA. Thus spherical agglomeration, a revered particle engineering technique, continues to be a salient approach for enhancing processability of high-dose drugs like ETB.