Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate
Jae Hong Seo, Jung Bae Park, Woong-Kee Choi, Sunhwa Park, Yun Jin Sung, Euichaul Oh, Soo Kyung Bae College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea Objective: Cilostazol is a Biopharmaceutical Classification Sy...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015-07-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/improved-oral-absorption-of-cilostazol-via-sulfonate-salt-formation-wi-peer-reviewed-article-DDDT |
| _version_ | 1819055966341038080 |
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| author | Seo JH Park JB Choi WK Park S Sung YJ Oh E Bae SK |
| author_facet | Seo JH Park JB Choi WK Park S Sung YJ Oh E Bae SK |
| author_sort | Seo JH |
| collection | DOAJ |
| description | Jae Hong Seo, Jung Bae Park, Woong-Kee Choi, Sunhwa Park, Yun Jin Sung, Euichaul Oh, Soo Kyung Bae College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea Objective: Cilostazol is a Biopharmaceutical Classification System class II drug with low solubility and high permeability, so its oral absorption is variable and incomplete. The aim of this study was to prepare two sulfonate salts of cilostazol to increase the dissolution and hence the oral bioavailability of cilostazol.Methods: Cilostazol mesylate and cilostazol besylate were synthesized from cilostazol by acid addition reaction with methane sulfonic acid and benzene sulfonic acid, respectively. The salt preparations were characterized by nuclear magnetic resonance spectroscopy. The water contents, hygroscopicity, stress stability, and photostability of the two cilostazol salts were also determined. The dissolution profiles in various pH conditions and pharmacokinetic studies in rats were compared with those of cilostazol-free base.Results: The two cilostazol salts exhibited good physicochemical properties, such as nonhygroscopicity, stress stability, and photostability, which make it suitable for the preparation of pharmaceutical formulations. Both cilostazol mesylate and cilostazol besylate showed significantly improved dissolution rate and extent of drug release in the pH range 1.2–6.8 compared to the cilostazol-free base. In addition, after oral administration to rats, cilostazol mesylate and cilostazol besylate showed increases in Cmax and AUCt of approximately 3.65- and 2.87-fold and 3.88- and 2.94-fold, respectively, compared to cilostazol-free base.Conclusion: This study showed that two novel salts of cilostazol, such as cilostazol mesylate and cilostazol besylate, could be used to enhance its oral absorption. The findings warrant further preclinical and clinical studies on cilostazol mesylate and cilostazol besylate at doses lower than the usually recommended dosage, so that it can be established as an alternative to the marketed cilostazol tablet. Keywords: BCS class II, cilostazol, besylate, mesylate, acid addition reaction, dissolution |
| first_indexed | 2024-12-21T13:15:55Z |
| format | Article |
| id | doaj.art-36eddd4ee266438c86847cd4a6373ef1 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-21T13:15:55Z |
| publishDate | 2015-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-36eddd4ee266438c86847cd4a6373ef12022-12-21T19:02:43ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-07-012015default3961396822875Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylateSeo JHPark JBChoi WKPark SSung YJOh EBae SKJae Hong Seo, Jung Bae Park, Woong-Kee Choi, Sunhwa Park, Yun Jin Sung, Euichaul Oh, Soo Kyung Bae College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea Objective: Cilostazol is a Biopharmaceutical Classification System class II drug with low solubility and high permeability, so its oral absorption is variable and incomplete. The aim of this study was to prepare two sulfonate salts of cilostazol to increase the dissolution and hence the oral bioavailability of cilostazol.Methods: Cilostazol mesylate and cilostazol besylate were synthesized from cilostazol by acid addition reaction with methane sulfonic acid and benzene sulfonic acid, respectively. The salt preparations were characterized by nuclear magnetic resonance spectroscopy. The water contents, hygroscopicity, stress stability, and photostability of the two cilostazol salts were also determined. The dissolution profiles in various pH conditions and pharmacokinetic studies in rats were compared with those of cilostazol-free base.Results: The two cilostazol salts exhibited good physicochemical properties, such as nonhygroscopicity, stress stability, and photostability, which make it suitable for the preparation of pharmaceutical formulations. Both cilostazol mesylate and cilostazol besylate showed significantly improved dissolution rate and extent of drug release in the pH range 1.2–6.8 compared to the cilostazol-free base. In addition, after oral administration to rats, cilostazol mesylate and cilostazol besylate showed increases in Cmax and AUCt of approximately 3.65- and 2.87-fold and 3.88- and 2.94-fold, respectively, compared to cilostazol-free base.Conclusion: This study showed that two novel salts of cilostazol, such as cilostazol mesylate and cilostazol besylate, could be used to enhance its oral absorption. The findings warrant further preclinical and clinical studies on cilostazol mesylate and cilostazol besylate at doses lower than the usually recommended dosage, so that it can be established as an alternative to the marketed cilostazol tablet. Keywords: BCS class II, cilostazol, besylate, mesylate, acid addition reaction, dissolutionhttp://www.dovepress.com/improved-oral-absorption-of-cilostazol-via-sulfonate-salt-formation-wi-peer-reviewed-article-DDDT |
| spellingShingle | Seo JH Park JB Choi WK Park S Sung YJ Oh E Bae SK Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate Drug Design, Development and Therapy |
| title | Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate |
| title_full | Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate |
| title_fullStr | Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate |
| title_full_unstemmed | Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate |
| title_short | Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate |
| title_sort | improved oral absorption of cilostazol via sulfonate salt formation with mesylate and nbsp besylate |
| url | http://www.dovepress.com/improved-oral-absorption-of-cilostazol-via-sulfonate-salt-formation-wi-peer-reviewed-article-DDDT |
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