In vitro and in vivo studies on the complexes of vinpocetine with hydroxypropyl-beta-cyclodextrin.
The purpose of this study was to evaluate complexes of vinpocetine (VIN), a poorly water-soluble base type drug, with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in aqueous environment and in solid state, with or without citric acid (CA) as an acidifier of the complexation medium. The apparent stability constant (Kc) calculated by phase solubility was 282 M(-1) and the complexation in solution was structurally characterized by 1H-NMR which showed VIN was likely to fit into the cyclodextrin cavity with its phenyl ring and ethyl ester bond. Solid complexes of VIN and HP-beta-CD were prepared by kneading (KE), co-evaporating (CE) and freeze-drying (FD) methods. Physical mixtures were prepared for comparison. The study in the solid state included the differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and infrared absorption spectroscopy (IR). From these analyses, CE and FD products were found in amorphous state, allowing to the conclusion of strong evidences of inclusion complex formation. However, the dissolution test showed that only VIN/HP-beta-CD+CA complexes by CE and FD method could provide satisfying dissolution behavior (rapid, complete and lasting) when compared to that of VIN/HP-beta-CD complexes. Interestingly, the addition of CA in inclusion complexes could significantly decrease the amount of HP-beta-CD needed to solubilize the same amount of VIN and thereby reducing the formulation bulk. Furthermore, in-vivo study revealed that the bioavailability of VIN after oral administration to rabbits (n=6) was significantly improved by VIN/HP-beta-CD+CA inclusion complex.
Nie
Shufang
S
Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua RD NO 103, Shenyang, China. niesf77@163.com
Fan
Xiaowen
X
Peng
Ying
Y
Yang
Xingang
X
Wang
Chao
C
Pan
Weisan
W
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011817:Rabbits; D012995:Solubility; D013055:Spectrophotometry, Infrared; D014748:Vinca Alkaloids / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000959:Antihypertensive Agents; D005079:Excipients; D014748:Vinca Alkaloids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C013983:vinpocetine