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Mechanochemical Synthesis of Drug-Drug and Drug-Nutraceutical Multicomponent Solids of Olanzapine

Abstract

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

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Article information


Submitted
23 Sep 2019
Accepted
31 Dec 2019
First published
08 Jan 2020

CrystEngComm, 2020, Accepted Manuscript
Article type
Paper

Mechanochemical Synthesis of Drug-Drug and Drug-Nutraceutical Multicomponent Solids of Olanzapine

K. K. Sarmah, N. Nath, D. R. Rao and R. Thakuria, CrystEngComm, 2020, Accepted Manuscript , DOI: 10.1039/C9CE01504C

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