Enhancement of Simvastatin ex vivo Permeation from Mucoadhesive Buccal Films Loaded with Dual Drug Release Carriers
Tarek A Ahmed,1,2 Alaa O Bawazir,1 Waleed S Alharbi,1 Martin K Safo3 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; 3Departmen...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2020
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| Acceso en línea: | https://doaj.org/article/4b08b87586664fbb85dbc1e4383f22ec |
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| Sumario: | Tarek A Ahmed,1,2 Alaa O Bawazir,1 Waleed S Alharbi,1 Martin K Safo3 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; 3Department of Medicinal Chemistry and the Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USACorrespondence: Tarek A AhmedDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi ArabiaTel +966 2 640 0000 Ext 22250Email tabdelnapy@kau.edu.saBackground: Simvastatin (SMV), a hypocholesterolemic agent, suffers from very low bioavailability due to its poor aqueous solubility and extensive first-pass metabolism.Methods: Two SMV carrier systems, namely, polymeric drug inclusion complex (IC) and mixed micelles (MM) nanoparticles, were developed and loaded into mucoadhesive buccal films to enhance SMV bioavailability. The two carrier systems were characterized and their permeation across human oral epithelial cells (OEC) was studied. The effect of IC to MM ratio (X1) and the mucoadhesive polymer concentration (X2) on the cumulative percent of drug released, elongation percent and the mucoadhesive strength, from the prepared mucoadhesive films, were optimized. Ex vivo permeation across bovine mucosal tissue was investigated. The permeation parameters for the in vitro and ex vivo release data were calculated.Results: Complexation of SMV with hydroxypropyl beta-cyclodextrin (HP β-CD) was superior to all other polymers as revealed by the equilibrium saturation solubility, stability constant, complexation efficiency and thermodynamic potential. SMV-HP β-CD IC was utilized to develop a saturated polymeric drug solution. Both carrier systems showed enhanced permeation across OEC when compared to pure drug. X1 and X2 were significantly affecting the characteristics of the prepared films. The optimized mucoadhesive buccal film formulation loaded with SMV IC and drug MM nanoparticles demonstrated superior ex vivo permeation when compared to the corresponding pure drug buccal film, and the calculated permeation parameters confirmed this finding.Conclusion: Mucoadhesive buccal films containing SMV IC and drug MM can be used to improve drug bioavailability; however, additional pharmacokinetic and pharmacodynamic studies are required.Keywords: simvastatin, inclusion complex, mixed micelles, optimization, buccal films |
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