Improving Biopharmaceutical Properties of Vinpocetine Through Cocrystallization

Abstract

Vinpocetine is a poorly water soluble weakly basic drug (pK = 7.1) used for the treatment of several cerebrovascular and cognitive disorders. Because existing formulations exhibit poor bioavailability and scarce absorption, a dosage form with improved pharmacokinetic properties is highly desirable. Cocrystallization represents a promising approach to generate diverse novel crystal forms and to improve the aqueous solubility and in turn the oral bioavailability. In this article, a novel ionic cocrystal of vinpocetine is described, using boric acid as a coformer, and fully characterized (by means of differential scanning calorimetry, solid-state nuclear magnetic resonance, powder and single-crystal X-ray diffraction, and powder dissolution test). Pharmacokinetic performance was also tested in a human pilot study. This pharmaceutical ionic cocrystal exhibits superior solubilization kinetics and modulates important pharmacokinetic values such as maximum concentration in plasma (C), time to maximum concentration (t), and area under the plasma concentration-time curve (AUC) of the poorly soluble vinpocetine and it therefore offers an innovative approach to improve its bioavailability.

Halogen and Hydrogen Bonding in Multicomponent Crystals of Tetrabromo-1H-Benzotriazole

“…In this context, we have recently shown that the formation of halogen-bonded API-CCF cocrystals is a further opportunity offered by this interaction in biopharmacology [29,30]. The relevance of this opportunity is confirmed by the numerous halogen-bonded cocrystals of pharmaceutical interest reported after our papers [31][32][33][34][35][36].…”

Recent advances in improving oral drug bioavailability by cocrystals

“…As another example of studies on the bioavailability of cocrystals in human, Golob and coworkers 128 reported vinpocetine-boric acid ionic cocrystal which remarkably improved in vitro powder dissolution in comparison to pure vinpocetine. The authors conducted the in vivo oral absorption studies in healthy human subjects.…”

The crystal structure of 6-methyl-3,20-dioxo-19-norpregna-4,6-dien-17-yl acetate–2,4-dihydroxybenzoic acid (1/1), C30H36O8

“…Therefore, it is important to establish effective methods for enhancing the dissolution and bioavailability of NOMAC. It is agreed that co-crystals form a vital part of the solidstate toolbox for improving the properties of older medicines [7][8][9][10]. To date, researchers have obtained many co-crystals of the steroids to improve their dissolution compared with the pure counterpart [11,12].…”