Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability
(1) Background: Solid dispersion (SD) can help increase the bioavailability of poorly water-soluble drugs. Meanwhile, apixaban (APX)—a new anticoagulation drug—has low water solubility (0.028 mg/mL) and low intestinal permeability (0.9 × 10<sup>−6</sup> cm/s across Caco-2 colonic cells),...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/3/907 |
| _version_ | 1797609489915969536 |
|---|---|
| author | Juseung Lee Jong-Ju Lee Seungyeol Lee Linh Dinh Hangyu Oh Sharif Md Abuzar Jun-Hyun Ahn Sung-Joo Hwang |
| author_facet | Juseung Lee Jong-Ju Lee Seungyeol Lee Linh Dinh Hangyu Oh Sharif Md Abuzar Jun-Hyun Ahn Sung-Joo Hwang |
| author_sort | Juseung Lee |
| collection | DOAJ |
| description | (1) Background: Solid dispersion (SD) can help increase the bioavailability of poorly water-soluble drugs. Meanwhile, apixaban (APX)—a new anticoagulation drug—has low water solubility (0.028 mg/mL) and low intestinal permeability (0.9 × 10<sup>−6</sup> cm/s across Caco-2 colonic cells), thus resulting in a low oral bioavailability of <50%; (2) Methods: To solve the drawbacks of conventional APX products, a novel SD of APX in Soluplus<sup>®</sup> was prepared, characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopy techniques and evaluated for its solubility, intestinal permeability and pharmacokinetic performance. (3) Results: The crystallinity of the prepared APX SD was confirmed. The saturation solubility and apparent permeability coefficient increased 5.9 and 2.54 times compared to that of raw APX, respectively. After oral administration to the rats, the bioavailability of APX SD was improved by 2.31-fold compared to that of APX suspension (4) Conclusions: The present study introduced a new APX SD that potentially exhibits better solubility and permeability, thus increasing APX’s bioavailability. |
| first_indexed | 2024-03-11T06:02:04Z |
| format | Article |
| id | doaj.art-4d28c721ec6142538b0d4055b7afa1b8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:02:04Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4d28c721ec6142538b0d4055b7afa1b82023-11-17T13:16:03ZengMDPI AGPharmaceutics1999-49232023-03-0115390710.3390/pharmaceutics15030907Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and PermeabilityJuseung Lee0Jong-Ju Lee1Seungyeol Lee2Linh Dinh3Hangyu Oh4Sharif Md Abuzar5Jun-Hyun Ahn6Sung-Joo Hwang7College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea(1) Background: Solid dispersion (SD) can help increase the bioavailability of poorly water-soluble drugs. Meanwhile, apixaban (APX)—a new anticoagulation drug—has low water solubility (0.028 mg/mL) and low intestinal permeability (0.9 × 10<sup>−6</sup> cm/s across Caco-2 colonic cells), thus resulting in a low oral bioavailability of <50%; (2) Methods: To solve the drawbacks of conventional APX products, a novel SD of APX in Soluplus<sup>®</sup> was prepared, characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopy techniques and evaluated for its solubility, intestinal permeability and pharmacokinetic performance. (3) Results: The crystallinity of the prepared APX SD was confirmed. The saturation solubility and apparent permeability coefficient increased 5.9 and 2.54 times compared to that of raw APX, respectively. After oral administration to the rats, the bioavailability of APX SD was improved by 2.31-fold compared to that of APX suspension (4) Conclusions: The present study introduced a new APX SD that potentially exhibits better solubility and permeability, thus increasing APX’s bioavailability.https://www.mdpi.com/1999-4923/15/3/907apixabananticoagulationsolid dispersionsolubility enhancementbioavailability enhancement |
| spellingShingle | Juseung Lee Jong-Ju Lee Seungyeol Lee Linh Dinh Hangyu Oh Sharif Md Abuzar Jun-Hyun Ahn Sung-Joo Hwang Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability Pharmaceutics apixaban anticoagulation solid dispersion solubility enhancement bioavailability enhancement |
| title | Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability |
| title_full | Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability |
| title_fullStr | Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability |
| title_full_unstemmed | Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability |
| title_short | Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability |
| title_sort | preparation of apixaban solid dispersion for the enhancement of apixaban solubility and permeability |
| topic | apixaban anticoagulation solid dispersion solubility enhancement bioavailability enhancement |
| url | https://www.mdpi.com/1999-4923/15/3/907 |
| work_keys_str_mv | AT juseunglee preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability AT jongjulee preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability AT seungyeollee preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability AT linhdinh preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability AT hangyuoh preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability AT sharifmdabuzar preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability AT junhyunahn preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability AT sungjoohwang preparationofapixabansoliddispersionfortheenhancementofapixabansolubilityandpermeability |