Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase
Yanfei Miao,1 Shihua Zhao,1 Jian Zuo,1 Jiqin Sun,1 Jingnan Wang2 1College of Chemistry and Chemical Engineering, Taishan University, Tai’an, People’s Republic of China; 2School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, People’s Republic of ChinaCorrespondence...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-05-01
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| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/reduced-the-food-effect-and-enhanced-the-oral-bioavailability-of-ivaca-peer-reviewed-fulltext-article-DDDT |
| _version_ | 1811257281395818496 |
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| author | Miao Y Zhao S Zuo J Sun J Wang J |
| author_facet | Miao Y Zhao S Zuo J Sun J Wang J |
| author_sort | Miao Y |
| collection | DOAJ |
| description | Yanfei Miao,1 Shihua Zhao,1 Jian Zuo,1 Jiqin Sun,1 Jingnan Wang2 1College of Chemistry and Chemical Engineering, Taishan University, Tai’an, People’s Republic of China; 2School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, People’s Republic of ChinaCorrespondence: Yanfei Miao, College of Chemistry and Chemical Engineering, Taishan University, Tai’an 271000, People’s Republic of China, Tel/Fax +86-0538-6713958, Email ouyang_miaoyanfei@126.comPurpose: The purpose of this work was to develop an ivacaftor self-nanoemulsion drug delivery system (IVA-SNEDDS) using the newly developed double headed miscellaneous lipid (DHML) as oil phase to reduce the food effect and inter-individual absorption variability of IVA.Methods: The lipids with the greatest solubility to IVA were selected as the oil phase of IVA-SNEDDS by saturation solubility method. Then, among different surfactants and co-surfactants, those with good emulsifying ability for the selected oil phase were selected, and the proportion of surfactant and co-surfactant was further selected by pseudo-ternary phase diagram. The prepared IVA-SNEDDS were screened and evaluated in vitro and in beagle dogs.Results: The optimized IVA-SNEDDS formulation consisting of DHML, Tween 80, and Transcutol HP with the weight ratio of 2:2:1 was physically stable and it was easy to disperse in water, pH 1.2 hydrochloric acid and pH 6.8 phosphate buffer solution, and generated a fine homogeneous nanoemulsion, with mean globule size less than 75 nm regardless of dilution ratio. In vitro drug release studies showed that the drug in IVA-SNEDDS could be completely released in a short time, while the drug release in IVA-suspension was less than 1% at 60 min. In vivo, using IVA-suspension (Fed) as a reference, the relative oral bioavailability of IVA-suspension (Fasted), IVA-SNEDDS (Fasted), and IVA-SNEDDS (Fed) were 23.35%, 153.63%, and 149.89%, respectively. This showed that IVA-SNEDDS could eliminate the positive food effect, improve the oral bioavailability, and reduce the IVA absorption difference between individuals.Conclusion: As the oil phase of SNEDDS, DHML can significantly improve the drug solubility and drug loading of IVA-SNEDDS. Moreover, DHML was easily emulsified and can effectively form a nanoemulsion in vivo and in vitro. The prepared IVA-SNEDDS can reduce the inter-individual absorption variability of IVA, eliminate its food effect and improve its oral bioavailability.Keywords: ivacaftor, food effect, self-nanoemulsion drug delivery system (SNEDDS), oral bioavailability, oil phase |
| first_indexed | 2024-04-12T17:54:58Z |
| format | Article |
| id | doaj.art-aa4ffeb294ac4211800b5cd11330239b |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-12T17:54:58Z |
| publishDate | 2022-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-aa4ffeb294ac4211800b5cd11330239b2022-12-22T03:22:24ZengDove Medical PressDrug Design, Development and Therapy1177-88812022-05-01Volume 161531154675469Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil PhaseMiao YZhao SZuo JSun JWang JYanfei Miao,1 Shihua Zhao,1 Jian Zuo,1 Jiqin Sun,1 Jingnan Wang2 1College of Chemistry and Chemical Engineering, Taishan University, Tai’an, People’s Republic of China; 2School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, People’s Republic of ChinaCorrespondence: Yanfei Miao, College of Chemistry and Chemical Engineering, Taishan University, Tai’an 271000, People’s Republic of China, Tel/Fax +86-0538-6713958, Email ouyang_miaoyanfei@126.comPurpose: The purpose of this work was to develop an ivacaftor self-nanoemulsion drug delivery system (IVA-SNEDDS) using the newly developed double headed miscellaneous lipid (DHML) as oil phase to reduce the food effect and inter-individual absorption variability of IVA.Methods: The lipids with the greatest solubility to IVA were selected as the oil phase of IVA-SNEDDS by saturation solubility method. Then, among different surfactants and co-surfactants, those with good emulsifying ability for the selected oil phase were selected, and the proportion of surfactant and co-surfactant was further selected by pseudo-ternary phase diagram. The prepared IVA-SNEDDS were screened and evaluated in vitro and in beagle dogs.Results: The optimized IVA-SNEDDS formulation consisting of DHML, Tween 80, and Transcutol HP with the weight ratio of 2:2:1 was physically stable and it was easy to disperse in water, pH 1.2 hydrochloric acid and pH 6.8 phosphate buffer solution, and generated a fine homogeneous nanoemulsion, with mean globule size less than 75 nm regardless of dilution ratio. In vitro drug release studies showed that the drug in IVA-SNEDDS could be completely released in a short time, while the drug release in IVA-suspension was less than 1% at 60 min. In vivo, using IVA-suspension (Fed) as a reference, the relative oral bioavailability of IVA-suspension (Fasted), IVA-SNEDDS (Fasted), and IVA-SNEDDS (Fed) were 23.35%, 153.63%, and 149.89%, respectively. This showed that IVA-SNEDDS could eliminate the positive food effect, improve the oral bioavailability, and reduce the IVA absorption difference between individuals.Conclusion: As the oil phase of SNEDDS, DHML can significantly improve the drug solubility and drug loading of IVA-SNEDDS. Moreover, DHML was easily emulsified and can effectively form a nanoemulsion in vivo and in vitro. The prepared IVA-SNEDDS can reduce the inter-individual absorption variability of IVA, eliminate its food effect and improve its oral bioavailability.Keywords: ivacaftor, food effect, self-nanoemulsion drug delivery system (SNEDDS), oral bioavailability, oil phasehttps://www.dovepress.com/reduced-the-food-effect-and-enhanced-the-oral-bioavailability-of-ivaca-peer-reviewed-fulltext-article-DDDTivacaftorfood effectself-nanoemulsion drug delivery system (snedds)oral bioavailabilityoil phase. |
| spellingShingle | Miao Y Zhao S Zuo J Sun J Wang J Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase Drug Design, Development and Therapy ivacaftor food effect self-nanoemulsion drug delivery system (snedds) oral bioavailability oil phase. |
| title | Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase |
| title_full | Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase |
| title_fullStr | Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase |
| title_full_unstemmed | Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase |
| title_short | Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase |
| title_sort | reduced the food effect and enhanced the oral bioavailability of ivacaftor by self nanoemulsifying drug delivery system snedds using a new oil phase |
| topic | ivacaftor food effect self-nanoemulsion drug delivery system (snedds) oral bioavailability oil phase. |
| url | https://www.dovepress.com/reduced-the-food-effect-and-enhanced-the-oral-bioavailability-of-ivaca-peer-reviewed-fulltext-article-DDDT |
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