ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Enhancing the antidiabetic and antidyslipidemic activity of a 1,5-diarylpyrazole by solid dispersion pre-formulation

Eduardo Hernández-Vázquez, Samuel Estrada-Soto, Norma Lumbreras-Zavala, Martín Mundo-Campuzano, Fabiola Chávez-Silva, Rafael Villalobos-Molina, and Francisco Hernández-Luis

Departamento de Química Orgánica, Instituto de Química, Universidad Nacional Autónoma de México, Mexico, México

E-mail: ehervaz@iquimica.unam.mx

Received: 1 December 2021  Accepted: 26 April 2022

Abstract:

Three 1,5-diarylpyrazoles were synthesized and pre-formulated with polyvinylpyrrolidone to enhance the antidiabetic activity, evaluated on in vivo non-insulin dependent diabetes mellitus model. Additionally, an in vivo subacute test was conducted to quantify antidiabetic, lipidic profile and antidyslipidemic activity. Spectroscopic techniques together with microscopy confirmed drug-carrier interaction. Notably, the antidiabetic activity of a dehalogenated pyrazole was twofold enhanced with the pre-formulation. This treatment also displayed antihyperglycemic activity without producing hypoglycemia, while a sub-acute study demonstrated that the solid dispersion has benefits in improving dyslipidemia, specifically reducing triacylglycerols, an effect scarcely observed with the reference drug metformin. Therefore, solid dispersion pre-formulation offers a simple but effective approach for enhancing the peripheral action of cannabinoid receptor 1 antagonist, thus minimizing undesired effects while enhancing antidiabetic and related metabolic properties.

Keywords: Cannabinoid receptor 1 antagonist; Solid dispersions; Povidone; Antidiabetic activity; Antidyslipidemic

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02260-7

Chemical Papers 76 (9) 5551–5560 (2022)