Stabilization of supersaturation for enhanced oral absorption of a BCS II drug efonidipine hydrochloride: Eudragit® L100-55-based amorphous solid dispersions

Abstract

Supersaturation is a widely employed strategy to improve the oral bioavailability of poorly soluble drugs, but its application is usually limited by rapid recrystallization. This study aimed to investigate the solubilization and crystallization-inhibitory effects of various polymers, including HPMCAS-LG, HPC-SL, HP-55, PVP K30, HPMC, and Eudragit® L100-55, on the BCS II drug efonidipine hydrochloride (EFH).

Eudragit® L100-55 demonstrated the most effective ability to generate and maintain supersaturation of EFH in pH 6.8 phosphate buffered saline. An organic solvent-free aqueous processing strategy was successfully employed to prepare amorphous solid dispersions (ASDs) of EFH. In vitro solubility studies showed that the Eudragit® L100-55 ASDs achieved significantly higher maximum drug concentrations than crude EFH and maintained supersaturation for a prolonged duration. Consequently, in vitro studies using everted gut sacs showed that the optimized ASD enhanced the apparent permeability of EFH by nearly threefold compared to the crude drug, while the apparent permeability was comparable to that of Landel®. Pharmacokinetic studies in beagle dogs confirmed a significant improvement in oral absorption.

The relative bioavailability of the optimized Eudragit® L100-55 ASD was approximately 1.5-fold higher than that of Landel®, although slightly lower C_max and delayed t_max values were observed, indicating a slower but more sustained absorption process. The prolonged MRT further supported extended systemic exposure. the relative bioavailability of the optimized Eudragit® L100-55 ASD were 1.5 times higher than that of Landel®. The prolonged t_max and MRT suggest modified drug release characteristics.

The findings demonstrate that Eudragit® L100-55-based ASDs prepared via aqueous processing represent a promising strategy for enhancing the intestinal absorption and oral bioavailability of EFH by effectively generating and stabilizing its supersaturated state. The enhancement is primarily attributed to sustained supersaturation, which maintains a higher concentration gradient and promotes absorptive flux across the intestinal membrane.

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Materials

EFH and efonidipine were supplied by Yonezawa Hamari Chemicals Co., Ltd. (Tokyo, Japan). Polyvinylpyrrolidone (PVP K30) was obtained from Ashland Specialty Ingredients (Wilmington, USA). Hydroxypropyl methylcellulose (HPMC SH90 4000SR), hydroxypropyl methylcellulose phthalate (HP-55) and hydroxypropyl methylcellulose acetate succinate (HPMCAS LG) were supplied by Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan). Eudragit® L100-55 was obtained from Evonik Operations GmbH (Darmstadt, Germany).

Song Huang, Yiqi Tian, Jiaxin Gao, Yuchen Zhang, Gang Cheng, Meijuan Zou, Hongyu Piao, Stabilization of supersaturation for enhanced oral absorption of a BCS II drug efonidipine hydrochloride: Eudragit® L100-55-based amorphous solid dispersions, Journal of Pharmaceutical Sciences, 2026, 104239, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2026.104239.