Impact of Microemulsion Oil Components on Liquid–Liquid Phase Separation of a Supersaturated Drug Revealed by Cryo-TEM and 1H NMR Analysis

• DOI: 10.1021/acs.molpharmaceut.4c01257
• Publication Date: 2025-02-14T10:55:06Z
• Authors: Risa Edera; Keisuke Ueda; Saeko Tomita; Kenjirou Higashi; Kunikazu Moribe
• Keywords: Microemulsion; Supersaturation

Supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) has recently been utilized to enhance the oral absorption of poorly water-soluble drugs. S-SMEDDS forms drug-incorporated microemulsions (MEs) during aqueous dispersion with formation supersaturation in bulk water phase. However, liquid–liquid phase separation (LLPS) behavior supersaturated drugs within MEs not well studied. This study investigated impact components on LLPS and achievable level MEs. Fenofibrate (FFB)-loaded formulations composed different oils, Labrafil M 1944 CS (M1944) Labrafac PG (PG), were prepared dispersed into form (M1944 ME ME). Cryo-TEM measurements revealed coexistence swelling micelles nanosized FFB-rich droplets highly FFB-loaded MEs, indicating that FFB underwent even The droplet size was significantly reduced ME. NMR-based quantification solubilized phase-separated apparent amorphous solubility increased increasing M1944 while almost constant regardless contents. On other hand, largely partitioned phase, resulting reduction chemical potential maximum free concentration mixing would work maintain as a smaller size. Meanwhile, minimally distributed keeping FFB. highlights oil physicochemical properties drug-rich formed via should be considered when designing absorption.