Effect of binders on polymorphic transformation kinetics of carbamazepine in aqueous solution

Abstract

The effects of binders on the polymorphic transformation kinetics of carbamazepine (CBZ) were investigated by thermal analysis and X-ray diffraction analysis. The binders used were hydroxypropylcellulose (HPC) (HPC-SL, molecular weight 30 000–50 000; HPC-M, molecular weight 50 000–70 000; HPC-L, molecular weight 110 000–150 000). CBZ anhydrate form I and various concentrations of binder solutions were mixed at 1000 rpm and 25°C. The amount of dihydrate transformed was evaluated based on the latent heat due to dehydration on DSC curves. Since the first-order plots for transformation process of CBZ showed a straight line, the transformation rate constant, k and induction period, IP were estimated based on first-order kinetics by the least-squares method. The k of CBZ decreased with increase of HPC-L concentration, but the IP increased. In contrast, the k of phase transformation on addition of crystal seeds was almost the same as that without seeds, but the IP significantly decreased on seed addition. The result suggested that IP was a nucleus formation process, but the seed addition did not affect the crystal growth process. The molecular weight effect of HPC on the transformation suggested that the k of HPC-SL was the largest, with the rank order being HPC-SL>HPC-M>HPC-L. The order for IP was HPC-L>HPC-SL>HPC-M. The relation between IP and kinematic viscosity had a straight line, but the k decreased with increase of kinematic viscosity. The increase of IP on addition of HPC might be induced by inhibition of the formation of nuclei by the steric intermolecular effect of HPC and decrease of Δ μ. Therefore, HPC strongly inhibited nucleus formation in the crystallization of CBZ.