Composition and Technology Development for Obtaining Amorphous Solid Dispersion of Ebastine by Hot Melt Extrusion to Increase Dissolution Rate

Abstract

Introduction. Ebastine is a second-generation antihistamine drug available in the form of orally disintegrating tablets and film-coated tablets. Ebastine substance exhibits high bioavailability, but low solubility in water and gastrointestinal tract media. The technology of solid dispersions based on polymer carriers by hot melt extrusion is proposed to solve the problem of ebastine low solubility.Aim. Composition development of extrudate and its production technology to create an amorphous solid dispersion of ebastine in oder to increase the recovery rate and bioavailability.Materials and methods. Ebastin micronized (JSC "Active Component", Russia); ebastin crystalline (Arevipharma GmbH, Germany); VIVAPHARM® PVP/VA 64 (JRS Pharma GMbH & Co. KG, Germany). Extrudates were obtained on a HAAKE™ miniCTW co-rotating twin-screw laboratory extruder (Thermo Fisher Scientific, Germany). Extrudates were studied by differential scanning calorimetry, synchronous thermal analysis, powder X-ray diffraction and FTIR-spectroscopy. The quantitative content of the active ingredient was determined by spectrophotometry. The content of related impurities in the amorphous solid dispersion of ebastine was determined by HPLC.Results and discussion. The technology of amorphous solid dispersion of ebastine by hot melt extrusion was developed. The pharmacokinetic properties of ebastine were significantly improved. The process of obtaining solid dispersion with 20 % of ebastine was optimized in order to reduce the content of impurities in the extrudate.Conclusion. The maximum concentration of ebastine for proper quality amorphous solid dispersion based on PVP/VA64 amounted to 20 %. Obtaining a solid dispersion by hot melt extrusion with ebastine content in PVP/VA64 higher than 30 % is impossible because the melt does not possess the glass transition property.