Acta Pharm. 68 (2018) 325-336

 

full paper

Original research paper

 

Dissolution rate enhancement of ketoconazole by liquisolid technique

MIR-ALI MOLAEI, KARIM OSOULI-BOSTANABAD, KHOSRO ADIBKIA, JAVAD SHOKRI, SOLMAZ ASNAASHARI and YOUSEF JAVADZADEH

javadzadehy@yahoo.com; javadzadehy@tbzmed.ac.ir

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 51664, Iran

2 Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz 51664, Iran

3 Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

4 Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664, Iran

5 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz 51664, Iran

Accepted March 15, 2018

Published online April 27, 2018

 

The study was conducted to enhance the dissolution rate of ketoconazole (KCZ) (a poorly water-soluble drug) using the liquisolid technique. Microcrystalline cellulose, colloidal silica, PEG400 and polyvinyl pyrrolidone (PVP) were employed as a carrier, coating substance, nonvolatile solvent and additive in the KCZ liquisolid compact formulation, respectively. The drug-to-PEG400 and carrier-to-coating ratio variations, PVP concentration and aging effects on the in vitro release behavior were assessed. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) data revealed no alterations in the crystalline form of the drug and the KCZ-excipient interactions within the process. The load factor and the drug release rate were significantly enhanced compared to directly compressed tablets in the presence of the additive. Increasing the PEG400-to-drug ratio in liquid medications enhanced the dissolution rate remarkably. The dissolution profile and hardness of liquisolid compacts were not significantly altered by keeping the tablets at 40 C and relative humidity of 75 % for 6 months. With the proposed modification of the liquisolid process, it is possible to obtain flowable, compactible liquisolid powders of high-dose poorly-water soluble drugs with an enhanced dissolution rate.

 

Keywords: ketoconazole, liquisolid, dissolution rate, Avicel, polymorphic changes