Development of a self-microemulsifying drug delivery system using a Dunnione to enhance bioavailability

• Published in: Journal of pharmaceutical investigation 2024, 54(5), , pp.605-615
• Main Authors: Hwang, Se Jung, Lee, Jeong Hyeon, Choi, Ji Hoon, Oh, Gi-Su, So, Hong-Seob, Park, Jun-Bom, Weon, Kwon Yeon
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Original Article; 약학
• ISSN: 2093-5552; 2093-6214
• DOI: 10.1007/s40005-024-00672-z

Purpose The purpose of this study was to enhance the solubility and oral bioavailability of Dunnione (DUN) using a self-microemulsifying drug delivery system (SMEDDS). Methods To determine the optimal formulation of the Dunnione-SMEDDS (DUN-SME), we assessed the solubility and compatibility of various oil and surfactant candidates. Subsequently, we employed the design of experiments (DoE) to optimize the formulation, considering the particle size distribution in water and the SMEDDS composition. The characteristics of the optimized DUN-SME were confirmed based on the particle size, zeta potential, and drug release profiles. Subsequently, we assessed the bioavailability of DUN-SME in Beagles conducting a pharmacokinetic study. Results Based on the results of the solubility study, the optimal formulation of DUN-SME comprised Capryol® 90, Tween 20, and Transcutol® P. In the compatibility test, all tested surfactants exhibited the characteristics necessary for organizing DUN-SME into self-emulsions and the formation of fine emulsions. Subsequently, we predicted a particle size of 29.3 nm for DUN-SME based on the simplex lattice design. The measured particle size was 13.7 nm, and the zeta potential was − 6.87 mV. We also confirmed enhanced drug dissolution within 60 min, which was approximately 2-fold higher than that of DUN alone. Furthermore, the bioavailability of DUN was 3.66-fold higher than that of DUN alone in Beagles. Conclusion The optimized DoE-based DUN-SME formulation showed improved solubility and oral bioavailability. Therefore, this strategy may offer a promising solution for developing oral dosage forms of DUN with poor solubility and bioavailability.