Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation

被引：6

作者：

Lee, Jaehyeok ^{[1
]}

Lee, Chul Haeng ^{[2
]}

Lee, Jong-Geon ^{[1
]}

Jeon, So Yeon ^{[2
]}

Choi, Min-Koo ^{[2
]}

Song, Im-Sook ^{[1
]}

机构：

[1] Kyungpook Natl Univ, BK21 FOUR Community Based Intelligent Novel Drug, Vessel Organ Interact Res Ctr VOICE, Res Inst Pharmaceut Sci,Coll Pharm, Daegu 41566, South Korea

[2] Dankook Univ, Coll Pharm, Cheonan Si 31116, South Korea

来源：

PHARMACEUTICS | 2022年 / 14卷 / 05期

基金：

新加坡国家研究基金会;

关键词：

ursodeoxycholate (UDCA); oral bioavailability; pH-modified extended release formulation; spray-drying method; BILE-ACIDS; INTESTINAL-ABSORPTION; PHOSPHOLIPID COMPLEX; IN-VITRO; LIVER; IMPROVEMENT; SOLUBILITY; DRUG; HEPATOCYTES; CHOLESTASIS;

D O I：

10.3390/pharmaceutics14051037

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：18

共 44 条

[41]

Yue PF, 2008, DRUG DEV IND PHARM, V34, P708, DOI [10.1080/03639040701842477, 10.1080/03639040701842477 ]

[42] Process optimization, characterization and pharmacokinetic evaluation in rats of ursodeoxycholic acid-phospholipid complex [J].