Studies on Influence of Polymers and Excipients on Crystallization Behavior of Metformin HCl to Improve the Manufacturability

Abstract

The aim of this work was to improve the mechanical properties of Metformin HCl by its recrystallization in the presence of different polymers and excipients using a wide range of polarity solvents. The recrystallized drug in the presence of lactose anhydrous (lactose) was further studied for its topographical, micromeritic, mechanical, compressional, solubility, and dissolution properties. Lactose-treated crystals were bigger in size with equidimentional shape. Crystals showed improvement in flow and packability with rich drug content (96.17%). Heckel parameters indicated greater plastic deformation (K = 0.474) and tensile strength compared to the pure drug (K = 0.137). Pellets prepared from crystals showed negligible elastic recovery (1.06%) compared to the pure drug (5.73%). Differential scanning calorimetry showed no degradation or polymorphic transformation of the drug even after stability studies (40°C, 75% RH). Fourier transform infrared spectroscopy proved hydrogen bond generation between the drug and lactose with a stable nature. The amount of directly compressible diluents could be minimized in tablet formulation, which ultimately reduced the overall tablet mass. The study highlights an influence of lactose on morphology, leading to a modified performance of recrystallized Metformin HCl.