Mechanochemical synthesis of drug–drug and drug–nutraceutical multicomponent solids of olanzapine

Abstract

Drug–drug and drug–nutraceutical multicomponent solids of an antipsychotic drug olanzapine (OLN) are prepared using mechanochemistry. Drug molecules, viz., nateglinide (NAT) and pyrazinoic acid (PZO) as well as nutraceuticals, namely, 2,4,6-trihydroxybenzoic acid (246THBA), gallic acid (GA) and sinapic acid (SPA) are used as coformers in this study. After neat grinding (NG), incomplete conversion (partially amorphous) was observed, whereas liquid-assisted grinding (LAG) resulted in the formation of coamorphous OLN–NAT and crystalline salts/salt hydrates of OLN with rest of the coformers, which were characterized using a combination of techniques, including single crystal X-ray diffraction. The OLN–NAT coamorphous salt has a potential scope for development as a combination drug in order to suppress the increase in the blood sugar level, a common side-effect observed during the monotherapy of psychiatric patients using OLN. The equilibrium solubility study shows a substantial enhancement in the solubility of olanzapinium pyrazinoate compared to that of the pure base.