Revaprazan-loaded surface-modified solid dispersion: physicochemical characterization and in vivo evaluation

Abstract

The purpose of this research was to develop a novel revaprazan-loaded surface-modified solid dispersion (SMSD) with improved drug solubility and oral bioavailability. The impact of carriers on aqueous solubility of revaprazan was investigated. HPMC and Cremophor A25 were selected as an appropriate polymer and surfactant, respectively, due to their high drug solubility. Numerous SMSDs were prepared with various concentrations of carriers, using distilled water, and the drug solubility of each was assessed. Moreover, the physicochemical properties, dissolution and pharmacokinetics of selected SMSD in rats were assessed in comparison to revaprazan powder. Of the SMSDs assessed, the SMSD composed of revaprazan/HPMC/Cremophor A25 at the weight ratio of 1:0.28:1.12 had the most enhanced drug solubility (∼6000-fold). It was characterized by particles with a relatively rough surface, suggesting that the carriers were attached onto the surface of the unchanged crystalline revaprazan powder. It had a significantly higher dissolution rate, AUC and C_max, and a faster T_max value in comparison to revaprazan powder, with a 5.3-fold improvement in oral bioavailability of revaprazan. Therefore, from an environmental perspective, this SMSD system prepared with water, and without organic solvents, should be recommended as a revaprazan-loaded oral pharmaceutical alternative.

Keywords:

• Revaprazan
• surface-modified solid dispersion
• unchanged crystalline
• drug solubility
• oral bioavailability

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by National Research Foundation (NRF) of South Korea grants funded by the South Korea government (MEST) [no. 2018R1A2B2004668] and a grant [16173MFDS542] from the Ministry of Food and Drug Safety in 2016.