Acta Pharm. 59 (2009) 187-197

full paper

Original research paper

Improvement of physicomechanical properties of carbamazepine by recrystallization at different pH values

YOUSEF JAVADZADEH, AMENEH MOHAMMADI, NAZANINOSSADAT SEYED KHOEI and ALI NOKHODCHI

javadzadehy@yahoo.com or javadzadehy@tbzmed.ac.ir

¹Faculty of Pharmacy and Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz 51664, Iran

²Medway School of Pharmacy, Central Ave., University of Kent and Greenwich, Chatham, Kent, ME4 4TB, England

Accepted March 25, 2009

The morphology of crystals has an appreciable impact on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviors of drugs. The objective of this study was to achieve improved physicomechanical properties of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressures and measuring their hardness. SEM studies showed that carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle-shaped. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature or pH of crystallization media. The crushing strength of tablets indicated that all the recrystallized carbamazepine samples had better compactibility than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate of carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.

Keywords: carbamazepine, crystalization, pH, polymorphism