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• W2044578448 startingPage "386" @default.
• W2044578448 abstract "The purpose of this paper was to study the solubility–permeability interplay in formulation development for oral administration of poor aqueous solubility drugs. The apparent solubility of the lipophilic drug carbamazepine was measured in systems containing various levels of the co-solvent PEG-400. The corresponding permeability was then measured in the PAMPA assay and in the rat jejunal perfusion model. Thermodynamic activity was maintained equivalent in all permeability studies (50% saturation). PEG-400 increased carbamazepine solubility in a concentration-dependent fashion. Decreased carbamazepine intestinal permeability with increased apparent solubility was observed in both PAMPA and rat perfusion models. Additionally, we have shown that the intestinal absorption of carbamazepine is membrane-controlled, with essentially no effective barrier function of the unstirred water layer. A mass transport analysis was employed to describe the solubility–permeability interplay. It was shown that the increased solubility in the aqueous GI milieu reduced the apparent membrane/aqueous partitioning, thereby reducing the driving force for membrane permeability. The model enabled excellent quantitative prediction of the effective permeability as a function of the solubility. In conclusion, a direct tradeoff between solubility increase and permeability decrease has been shown, which has to be accounted for when developing oral formulation for lipophilic drugs." @default.
• W2044578448 created "2016-06-24" @default.
• W2044578448 creator A5029193787 @default.
• W2044578448 creator A5046452207 @default.
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• W2044578448 date "2012-06-01" @default.
• W2044578448 modified "2023-10-01" @default.
• W2044578448 title "Accounting for the solubility–permeability interplay in oral formulation development for poor water solubility drugs: The effect of PEG-400 on carbamazepine absorption" @default.
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• W2044578448 doi "https://doi.org/10.1016/j.ejpb.2012.02.012" @default.
• W2044578448 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22387337" @default.
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