title: Improving Biopharmaceutical Properties of Vinpocetine Through Cocrystallization.
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.
authors: Department of Chemical and Pharmaceutical Sciences, University of Trieste, Italy.
authors: Samuel
authors: S
authors: Golob
authors: Department of Chemical & Environmental Sciences, University of Limerick, Limerick, Republic of Ireland.
authors: Miranda
authors: M
authors: Perry
authors: Department of Chemical & Environmental Sciences, University of Limerick, Limerick, Republic of Ireland.
authors: Matteo
authors: M
authors: Lusi
authors: Department of Chemistry and NIS Centre, University of Torino, Torino, Italy.
authors: Michele R
authors: MR
authors: Chierotti
authors: The Chair of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia.
authors: Iztok
authors: I
authors: Grabnar
authors: Department of Chemical and Pharmaceutical Sciences, University of Trieste, Italy.
authors: Lucia
authors: L
authors: Lassiani
authors: Department of Chemical and Pharmaceutical Sciences, University of Trieste, Italy. Electronic address: vojnovic@units.it.
authors: Dario
authors: D
authors: Voinovich
authors: Department of Chemical & Environmental Sciences, University of Limerick, Limerick, Republic of Ireland. Electronic address: xtal@ul.ie.
authors: Michael J
authors: MJ
authors: Zaworotko
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001702:Biopharmaceutics; D001888:Boric Acids / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization; D006801:Humans; D008297:Male; D008875:Middle Aged; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D001888:Boric Acids; D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C013983:vinpocetine; C032688:boric acid
keywords: bioavailability; boric acid; ionic cocrystal; pharmacokinetics; vinpocetine