Evaluation of physico-mechanical properties of drug-excipients agglomerates obtained by crystallization.

Abstract

Spherical crystallization (SC) of carbamazepine (CBZ) was carried out for preparation of the agglomerates using the solvent change method. The potential of the intraagglomerate addition of sodium starch glycolate (SSG) as a disintegrant agent and povidone (PVP) as a hydrophilic polymer was also evaluated. The process of SC involved recrystallization of CBZ and its simultaneous agglomeration with additives. An ethanol:isopropyl acetate:water system was used where isopropyl acetate acted as a bridging liquid and ethanol and water as good and bad solvents, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and Scanning electron microscopy and were evaluated for yield, flowability, disintegration time and drug release. CBZ agglomerates exhibited significantly improved micromeritic properties as well as dissolution behavior in comparison to conventional drug crystals. The dissolution rate of drug from agglomerates was enhanced by inclusion of SSG, while addition of PVP to CBZ/SSG agglomerates led to reduction in the release rate of CBZ even below that of the conventional drug crystals. SC process can be considered as a suitable alternative to conventional granulation process to obtain agglomerates of CBZ with excipients with improved micromeritic properties and modified dissolution rate.