Development and optimization of ketoconazole oral strips by means of continuous hot-melt extrusion processing.

Abstract

The aim of this study was to develop mucoadhesive oral strips using hot-melt extrusion as a continuous manufacturing process. Powder blends of ketoconazole, a water-insoluble drug - either hydroxypropyl methylcellulose (HPMC) or soluplus (SOL), sorbitol (SRB) and magnesium aluminometasilicate (MAS) were extruded to manufacture thin strips with 0.5-mm thickness. The presence of the inorganic metasilicate facilitated smooth processing of the extruded strips as it worked as an absorbent directly impacting on the extensive mixing of the drug/excipients inside the extruder barrel. The use of MAS also favoured the rapid hydration, swelling and eventual disintegration of the strips. Differential scanning calorimetry and transmission X-ray diffraction analysis revealed the existence of the amorphous drug within the extruded strips. Scanning electron microscopy and energy dispersive X-ray undertaken on the formulations showed a homogeneous drug distribution within the extruded strips. The strips produced via continuous hot-melt extrusion processing showed significantly faster release of ketoconazole compared to the bulk drug substance.