The effect of co-crystallization and polymorphism on the physicochemical properties of amoxicillin tri-hydrate

Magister Pharmaceuticae - MPharmMany active pharmaceutical ingredients (APIs) have poor physicochemical properties such as solubility, dissolution and chemical stability. Several strategies are used to enhance and improve these properties of the API. Co-crystallization and polymorphism studies are possible strategy used in pre-formulation studies to optimize these properties of the drug without modifying its pharmacological effect. The purpose of this research was to investigate the polymorphism and co-crystallization effects of the penicillin-type antibiotic, amoxicillin tri-hydrate. Several techniques such as: slow evaporation, slow cooling, vapour diffusion, sublimation, grinding and solvent assisted grinding was employed. In producing co-crystals, the API was non-covalently bound to selected co-formers such as: saccharin, nicotinamide, salicylic acid, L-tartaric acid, D-tartaric acid, L-aspartic acid, stearic acid, benzoic anhydride, oxalic acid di-hydrate, cinnamic acid, succinic acid and citric acid monohydrate. Nine co-crystals of amoxicillin tri-hydrate had been formed. Differential scanning calorimetry (DSC), hot stage microscopy (HSM) and thermal gravimetric analysis (TGA) was conducted to analyse the thermal behaviour of the co-crystals. Powder X-ray diffraction (PXRD) and spectroscopic techniques [infra-red (FTIR) and H1-nuclear magnetic resonance (H1MNR)] were employed for screening of the co-crystal forms. Furthermore, dissolution testing was conducted to investigate the application of the newly derivatised forms