Improved micromeritics, packing properties and compressibility of high dose drug, Cycloserine, by spherical crystallization

Abstract

Cycloserine, a high dose anti-tuberculosis agent, possesses poor flow properties and compression behaviour. The present study was aimed at improving the flowability, packing properties and compressibility of Cycloserine by spherical crystallization. Cycloserine was dissolved in a water and crystallised by pouring into anti-solvent, 1-Butanol, in presence of ethyl acetate which acts as a bridging liquid for formation of agglomeration. Further, spherical agglomeration process for Cycloserine was statistically optimized using the central composite design, keeping the ‘rate of stirring’ and ‘amount of bridging liquid’ as an independent factors and average particle size as the response. Optimized batch of Cycloserine spherical agglomerates (Cyc-SA) was further evaluated for sieve analysis, solid state characterization studies and compaction behaviour (Kawakita analysis and Heckel study). The uniform spherical agglomerates were revealed in microphotographs of scanning electron microscopy while no chemical alteration in the Cycloserine was indicated by X-Ray powder diffraction, differential scanning calorimetry and Fourier-transform infrared spectroscopy during the crystallization. The excellent flow properties of Cyc-SA were demonstrated by Carr's index, Hausner ratio and Kawakita parameters as compare to plain drug. The enhanced particle size and uniform distribution of agglomerates have also contributed to improve flow properties of Cycloserine. Similarly, Heckel parameters like mean yield pressure and yield strength displayed superior compressibility of Cyc-SA. Thus, spherical crystallization would be interesting technique for improving processability of high dose drug like Cycloserine.