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

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.