1. Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation
- Author
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Jaehyeok Lee, Chul Haeng Lee, Jong-Geon Lee, So Yeon Jeon, Min-Koo Choi, and Im-Sook Song
- Subjects
ursodeoxycholate (UDCA) ,oral bioavailability ,pH-modified extended release formulation ,spray-drying method ,Pharmacy and materia medica ,RS1-441 - Abstract
Ursodeoxycholate (UDCA) has low oral bioavailability and pH-dependent solubility and permeability. Thus, we developed a pH-modified extended-release formulation of UDCA using Na2CO3 as the alkalizing agent and hydroxypropyl methylcellulose (HPMC) as the release-modifying agent. The optimized pH-modified controlled-release UDCA formulation, with the UDCA:HPMC:Na2CO3 ratio of 200:600:150 (w/w/w), was prepared using a spray-drying method. Then, the formulation’s solubility, dissolution, and pharmacokinetic properties were characterized. In a pH-modified extended-release formulation of UDCA, the solubility of UDCA was increased to 8 mg/mL with a sustained dissolution for 12 h. Additionally, the spray-dried formulation exhibited amorphous states without molecular interaction among UDCA, Na2CO3, and HPMC. Moreover, the plasma UDCA concentration of the formulation maintained a higher UDCA concentration for up to 48 h than that of UDCA itself or the non-extended-release UDCA formulation. Consequently, the formulation significantly increased the AUC compared to UDCA or the non-extended-release UDCA formulation in rats. In conclusion, we have improved UDCA’s solubility and dissolution profile by preparing a pH-modified extended-release formulation with the UDCA:HPMC:Na2CO3 ratio of 200:600:150 (w/w/w), which effectively increased the oral bioavailability of UDCA by 251% in rats.
- Published
- 2022
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