Title:Improved Oral Bioavailability of Lacidipine Using Nanosuspension Technology: Inferior in vitro Dissolution and Superior in vivo Drug Absorption versus Lacipil®
VOLUME: 13 ISSUE: 5
Author(s):Juanhang Zhao, Lei Luo, Qiang Fu, Bei Guo, Yun Li, Yajie Geng, Junfeng Wang and Tianhong Zhang
Affiliation:Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Keywords:Bioavailability, Dissolution, In vitro, In vivo, Lacidipine, Nanosuspension.
Abstract:Improved dissolution is a better way of increasing the oral absorption of lacidipine (LCDP)
because it is a BCS II class drug. The purpose of this study is to improve the oral bioavailability of
LCDP by applying nanosuspension technology. LCDP nanosuspensions were prepared by a hybrid
method of microprecipitation and high pressure homogenization. The effects of the production parameters
(shearing rate and time, the stabilizers and their concentrations, homogenization pressure and
number of cycles) were investigated to optimize the preparation process. In vitro characterizations (X-ray powder diffraction,
differential scanning calorimetry, scanning electron microscopy and dissolution measurement) were carried out and
an oral pharmacokinetic study was performed in beagle dogs. LCDP was transformed into an amorphous state during the
preparation process, and the mean particle size was about 714.0 ± 12.7 nm. The dissolution rate of LCDP nanosuspensions
was faster than that of physical mixtures, but slower than that of Lacipil® (the commercial tablet). Regarding the in vivo
pharmacokinetics, the key pharmacokinetic parameters (Cmax and AUC0−∞) of the nanosuspensions were statistically significantly
higher than those of both the commercial tablet and physical mixtures. So, this is an efficient drug delivery
strategy to facilitate the oral administration of LCDP by using nanosuspension technology, and should be generally applicable
to many poorly water-soluble drugs with dissolution rate-limited absorption.
