Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan
Telmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispe...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/1/73 |
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| author | Bhupendra Raj Giri Jaewook Kwon Anh Q. Vo Ajinkya M. Bhagurkar Suresh Bandari Dong Wuk Kim |
| author_facet | Bhupendra Raj Giri Jaewook Kwon Anh Q. Vo Ajinkya M. Bhagurkar Suresh Bandari Dong Wuk Kim |
| author_sort | Bhupendra Raj Giri |
| collection | DOAJ |
| description | Telmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispersion (TEL pH<sub>M</sub>-SD) using hot-melt extrusion (HME) technology. We prepared different TEL pH<sub>M</sub>-SD formulations by varying the ratio of the drug (TEL, 10–60% <i>w</i>/<i>w</i>), the hydrophilic polymer (Soluplus<sup>®</sup>, 30–90% <i>w/w</i>), and pH-modifier (sodium carbonate, 0–10% <i>w</i>/<i>w</i>). More so, the tablets prepared from an optimized formulation (F8) showed a strikingly improved in vitro dissolution profile (~30-fold) compared to the free drug tablets. The conversion of crystalline TEL to its amorphous state is observed through solid-state characterizations. During the stability study, F8 tablets had a better stability profile compared to the commercial product with F8, showing higher drug content, low moisture content, and negligible physical changes. Moreover, compared to the TEL powder, in vivo pharmacokinetic studies in rats showed superior pharmacokinetic parameters, with maximum serum concentration (C<sub>max</sub>) and area under the drug concentration–time curve (AUC<sub>0</sub>–<sub>∞</sub>) of the TEL pH<sub>M</sub>-SD formulation increasing by 6.61- and 5.37-fold, respectively. Collectively, the results from the current study showed that the inclusion of a hydrophilic polymer, pH modulator, and the amorphization of crystalline drugs in solid dispersion prepared by HME can be an effective strategy to improve the solubility and bioavailability of hydrophobic drugs without compromising the drug’s physical stability. |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T04:27:11Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-cb7abd78f9974b5795e451f6b9c6ac4c2023-12-03T13:39:51ZengMDPI AGPharmaceuticals1424-82472021-01-011417310.3390/ph14010073Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of TelmisartanBhupendra Raj Giri0Jaewook Kwon1Anh Q. Vo2Ajinkya M. Bhagurkar3Suresh Bandari4Dong Wuk Kim5College of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Kyungpook National University, Daegu 41566, KoreaDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USADepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USADepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USACollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Kyungpook National University, Daegu 41566, KoreaTelmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispersion (TEL pH<sub>M</sub>-SD) using hot-melt extrusion (HME) technology. We prepared different TEL pH<sub>M</sub>-SD formulations by varying the ratio of the drug (TEL, 10–60% <i>w</i>/<i>w</i>), the hydrophilic polymer (Soluplus<sup>®</sup>, 30–90% <i>w/w</i>), and pH-modifier (sodium carbonate, 0–10% <i>w</i>/<i>w</i>). More so, the tablets prepared from an optimized formulation (F8) showed a strikingly improved in vitro dissolution profile (~30-fold) compared to the free drug tablets. The conversion of crystalline TEL to its amorphous state is observed through solid-state characterizations. During the stability study, F8 tablets had a better stability profile compared to the commercial product with F8, showing higher drug content, low moisture content, and negligible physical changes. Moreover, compared to the TEL powder, in vivo pharmacokinetic studies in rats showed superior pharmacokinetic parameters, with maximum serum concentration (C<sub>max</sub>) and area under the drug concentration–time curve (AUC<sub>0</sub>–<sub>∞</sub>) of the TEL pH<sub>M</sub>-SD formulation increasing by 6.61- and 5.37-fold, respectively. Collectively, the results from the current study showed that the inclusion of a hydrophilic polymer, pH modulator, and the amorphization of crystalline drugs in solid dispersion prepared by HME can be an effective strategy to improve the solubility and bioavailability of hydrophobic drugs without compromising the drug’s physical stability.https://www.mdpi.com/1424-8247/14/1/73telmisartanpH-modifiersolid dispersionhot-melt extrusion (HME)solubilitybioavailability |
| spellingShingle | Bhupendra Raj Giri Jaewook Kwon Anh Q. Vo Ajinkya M. Bhagurkar Suresh Bandari Dong Wuk Kim Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan Pharmaceuticals telmisartan pH-modifier solid dispersion hot-melt extrusion (HME) solubility bioavailability |
| title | Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan |
| title_full | Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan |
| title_fullStr | Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan |
| title_full_unstemmed | Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan |
| title_short | Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan |
| title_sort | hot melt extruded amorphous solid dispersion for solubility stability and bioavailability enhancement of telmisartan |
| topic | telmisartan pH-modifier solid dispersion hot-melt extrusion (HME) solubility bioavailability |
| url | https://www.mdpi.com/1424-8247/14/1/73 |
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