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Improved Oral Bioavalability of Mebudipine Upon Administration in PhytoSolve and Phosal-Based Formulation (PBF)

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Abstract

The aim of this investigation was to examine the efficacy of PhytoSolve and Phosal-based formulation (PBF) to enhance the oral bioavailability of mebudipine, which is a poorly water-soluble calcium channel blocker. The solubility of mebudipine in various oils was determined. PhytoSolve was prepared with a medium-chain triglyceride (MCT) oil (20%), soybean phospholipids (5%), and a 70% fructose solution (75%). The influence of the weight ratio of Phosal 50PG to glycerol in PBF on the mean globule size was studied with dynamic light scattering. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, and zeta potential. The in vivo oral absorption of different mebudipine formulations (PhytoSolve, PBF, oily solution, and suspension) were evaluated in rats. The optimized PBF contained Phosal 50PG/glycerol in a 6:4 ratio (w/w). The PBF and PhytoSolve formulations were miscible with water in any ratio and did not demonstrate any phase separation or drug precipitation over 1 month of storage. The mean particle size of PhytoSolve and PBF were 138.5 ± 9.0 and 74.4 ± 2.5 nm, respectively. The in vivo study demonstrated that the oral bioavailability of PhytoSolve and PBF in rats was significantly higher than that of the other formulations. The PhytoSolve and PBF formulations of mebudipine are found to be more bioavailable compared with suspension and oily solutions during an in vivo study in rats. These formulations might be new alternative carriers that increase the oral bioavailability of poorly water-soluble molecules, such as mebudipine.

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ACKNOWLEDGMENTS

This study was a portion of Dr. Samira Khani's Ph.D. thesis, which was supported by the Tehran University of Medical Sciences and fully funded by the Phospholipid Research Center (PRC), Heidelberg. The authors gratefully acknowledge the support received from the PRC throughout the project. The authors are also thankful to Lipoid GmbH supplying key materials.

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  1. Pharmacology Department, Tehran University of Medical Sciences, Hemmat Pardis, Tehran, Iran

    Samira Khani & Fariborz Keyhanfar

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  1. Samira Khani
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  2. Fariborz Keyhanfar
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Correspondence to Fariborz Keyhanfar.

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Khani, S., Keyhanfar, F. Improved Oral Bioavalability of Mebudipine Upon Administration in PhytoSolve and Phosal-Based Formulation (PBF). AAPS PharmSciTech 15, 96–102 (2014). https://doi.org/10.1208/s12249-013-0039-x

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  • DOI: https://doi.org/10.1208/s12249-013-0039-x

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