Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation
Ursodeoxycholate (UDCA) has low oral bioavailability and pH-dependent solubility and permeability. Thus, we developed a pH-modified extended-release formulation of UDCA using Na<sub>2</sub>CO<sub>3</sub> as the alkalizing agent and hydroxypropyl methylcellulose (HPMC) as the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/5/1037 |
| _version_ | 1797496665948553216 |
|---|---|
| author | Jaehyeok Lee Chul Haeng Lee Jong-Geon Lee So Yeon Jeon Min-Koo Choi Im-Sook Song |
| author_facet | Jaehyeok Lee Chul Haeng Lee Jong-Geon Lee So Yeon Jeon Min-Koo Choi Im-Sook Song |
| author_sort | Jaehyeok Lee |
| collection | DOAJ |
| description | Ursodeoxycholate (UDCA) has low oral bioavailability and pH-dependent solubility and permeability. Thus, we developed a pH-modified extended-release formulation of UDCA using Na<sub>2</sub>CO<sub>3</sub> 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:Na<sub>2</sub>CO<sub>3</sub> ratio of 200:600:150 (<i>w</i>/<i>w</i>/<i>w</i>), 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, Na<sub>2</sub>CO<sub>3</sub>, 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:Na<sub>2</sub>CO<sub>3</sub> ratio of 200:600:150 (<i>w</i>/<i>w</i>/<i>w</i>), which effectively increased the oral bioavailability of UDCA by 251% in rats. |
| first_indexed | 2024-03-10T03:06:52Z |
| format | Article |
| id | doaj.art-b70fa7f7453d4fe4b4eb0c44613ed8d7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:06:52Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b70fa7f7453d4fe4b4eb0c44613ed8d72023-11-23T12:38:33ZengMDPI AGPharmaceutics1999-49232022-05-01145103710.3390/pharmaceutics14051037Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release FormulationJaehyeok Lee0Chul Haeng Lee1Jong-Geon Lee2So Yeon Jeon3Min-Koo Choi4Im-Sook Song5BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Vessel-Organ Interaction Research Center (VOICE), Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Dankook University, Cheonan-si 31116, KoreaBK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Vessel-Organ Interaction Research Center (VOICE), Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Dankook University, Cheonan-si 31116, KoreaCollege of Pharmacy, Dankook University, Cheonan-si 31116, KoreaBK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Vessel-Organ Interaction Research Center (VOICE), Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, KoreaUrsodeoxycholate (UDCA) has low oral bioavailability and pH-dependent solubility and permeability. Thus, we developed a pH-modified extended-release formulation of UDCA using Na<sub>2</sub>CO<sub>3</sub> 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:Na<sub>2</sub>CO<sub>3</sub> ratio of 200:600:150 (<i>w</i>/<i>w</i>/<i>w</i>), 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, Na<sub>2</sub>CO<sub>3</sub>, 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:Na<sub>2</sub>CO<sub>3</sub> ratio of 200:600:150 (<i>w</i>/<i>w</i>/<i>w</i>), which effectively increased the oral bioavailability of UDCA by 251% in rats.https://www.mdpi.com/1999-4923/14/5/1037ursodeoxycholate (UDCA)oral bioavailabilitypH-modified extended release formulationspray-drying method |
| spellingShingle | Jaehyeok Lee Chul Haeng Lee Jong-Geon Lee So Yeon Jeon Min-Koo Choi Im-Sook Song Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation Pharmaceutics ursodeoxycholate (UDCA) oral bioavailability pH-modified extended release formulation spray-drying method |
| title | Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation |
| title_full | Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation |
| title_fullStr | Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation |
| title_full_unstemmed | Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation |
| title_short | Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation |
| title_sort | enhancing dissolution and oral bioavailability of ursodeoxycholic acid with a spray dried ph modified extended release formulation |
| topic | ursodeoxycholate (UDCA) oral bioavailability pH-modified extended release formulation spray-drying method |
| url | https://www.mdpi.com/1999-4923/14/5/1037 |
| work_keys_str_mv | AT jaehyeoklee enhancingdissolutionandoralbioavailabilityofursodeoxycholicacidwithaspraydriedphmodifiedextendedreleaseformulation AT chulhaenglee enhancingdissolutionandoralbioavailabilityofursodeoxycholicacidwithaspraydriedphmodifiedextendedreleaseformulation AT jonggeonlee enhancingdissolutionandoralbioavailabilityofursodeoxycholicacidwithaspraydriedphmodifiedextendedreleaseformulation AT soyeonjeon enhancingdissolutionandoralbioavailabilityofursodeoxycholicacidwithaspraydriedphmodifiedextendedreleaseformulation AT minkoochoi enhancingdissolutionandoralbioavailabilityofursodeoxycholicacidwithaspraydriedphmodifiedextendedreleaseformulation AT imsooksong enhancingdissolutionandoralbioavailabilityofursodeoxycholicacidwithaspraydriedphmodifiedextendedreleaseformulation |