Improving Biopharmaceutical Properties of Vinpocetine Through Cocrystallization

J Pharm Sci. 2016 Dec;105(12):3626-3633. doi: 10.1016/j.xphs.2016.09.017. Epub 2016 Oct 24.

Abstract

Vinpocetine is a poorly water soluble weakly basic drug (pKa = 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 (Cmax), time to maximum concentration (tmax), 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.

Keywords: bioavailability; boric acid; ionic cocrystal; pharmacokinetics; vinpocetine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Biopharmaceutics
  • Boric Acids / administration & dosage
  • Boric Acids / blood*
  • Boric Acids / chemistry*
  • Calorimetry, Differential Scanning / methods
  • Crystallization
  • Humans
  • Male
  • Middle Aged
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / blood
  • Vasodilator Agents / chemistry
  • Vinca Alkaloids / administration & dosage
  • Vinca Alkaloids / blood*
  • Vinca Alkaloids / chemistry*
  • X-Ray Diffraction / methods

Substances

  • Boric Acids
  • Vasodilator Agents
  • Vinca Alkaloids
  • vinpocetine
  • boric acid