Acta Pharm. 68 (2018) 325-336
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