Abstract
The effects of polymorphic forms of bulk powder on the pharmaceutical properties of carbamazepine (CBZ)granules were investigated by using X-ray diffraction analysis, thermal analysis and Brunauer-Emmett-Teller surface area measurement. A mixture consisting of 50% CBZ forms I, II, III or IV (dehydrate) as a bulk powder, 35% crystalline α-lactose monohydrate and 15% corn starch was used as a pharmaceutical powder, with binder aqueous solutions containing 5% hydroxypropylcellulose (HPC). After kneading with the binder solution, granules were obtained using an extruding granulator. After granulation forms I, II and III were 2.5, 80.3 and 35.2%transformed into dihydrate, respectively. Next, the wet granules were dried at 60°C for 24 h, and the transformed dihydrates were dehydrated into fine particles containing form III. The yield of granules obtained from forms I, II, III and IV was 73.8, 0.0, 0.0 and 76.3%, respectively. The lower granule yields of forms II and III appeared to be due to a lack of kneading water due to absorption of CBZ as crystalline water. Therefore, to the granules of forms II and III was added extra water (60 and 30 ml/kg) to the mixture, respectively, which improved yield markedly, (to 65.1 and 69.2%), indicating the decrease in granule yield was caused by the absorption of water on transformation of dihydrate. The specific surface area (Sw) results suggested that the granules obtained from form II bulk powder had the largest Sw, and those from form I the lowest. In the order of Sw and tablet hardness of the granules, the powders ranked form II>III>IV>I. This indicated that the mechanical strength of the tablet was proportional to the Sw of the particles. The dissolution profiles of the CBZ tablets were investigated in JP XIII, 1st fluid (ph 1.2, 37±0.5°C), and the time required for 50% dissolution (T50) was measured. In the order of T50 ranking was IV≤I<III<II. These results suggested that the polymorphic transformation during the granulation and drying processes induced a change in pharmaceutical properties.
