A Tablet as an Environment for Investigation of the Reactions in the Solid States

Objective In this study, a tablet’s matrix was considered a solid environment to investigate the reactions in the solid states. The tendency of molecules to each other and their interaction in the solid state was studied through the advent of impurities in the tablet caused by the interaction of the active pharmaceutical ingredient with an excipient. Significance Investigation of solid-state reactions and their prediction in the matrix of tablets will reveal the possible appearance of impurities in pharmaceutical dosage forms and help formulators prevent impurities in drug products. Methods Principal Component Analysis (PCA) was used to predict the interaction between Gliclazide as a secondary amine and Lactose in the manufactured powders. The infrared spectra of binary mixtures of Gliclazide with Lactose at different weight ratios were recorded and the obtained data matrix was analyzed with PCA. High-performance Liquid Chromatography (HPLC) was used for the identification and quantification of the impurity. Results The incompatibility was seen theoretically by PCA and also experimentally by HPLC. A kinetic model was proposed for this solid-state reaction in the tablets. The presence of some excipients was investigated on the appearance of the impurity and also on the kinetics of the reaction. This reaction was faster when Hydroxypropylmethylcellulose (HPMC) was present in the tablet formulation. Conclusion The chemical reaction in a tablet could be considered as a solid-state reaction. This reaction was predicted and modeled and the effect of the matrix of the tablet was investigated on the reaction.