Enhancement of ketoconazole dissolution rate by the liquisolid technique

Molaei, Mir-Ali and Osouli-Bostanabad, Karim and Adibkia, Khosro and Shokri, Javad and Asnaashari, Solmaz and Javadzadeh, Yousef (2018) Enhancement of ketoconazole dissolution rate by the liquisolid technique. Acta Pharmaceutica, 68 (3). 325–336. ISSN 1846-9558 (https://doi.org/10.2478/acph-2018-0025)

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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 em-ployed 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 scan-ning 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 sig-nificantly enhanced compared to directly compressed tab-lets 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 al-tered 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, com-pactible liquisolid powders of high-dose poorly-water soluble drugs with an enhanced dissolution rate.