Abstract

Purpose:Felodipine is a calcium channel antagonist, which is water insoluble and only 15% bioavailable when administered orally. In this study softgels, with a solubilized-drug core, were used to improve the solubility and consequently the bioavailability of felodipine. Drug solutions were prepared using both cosolvency and micellar solubilization. Methods:The optimum dielectric constant (DEC) for maximum drug solubility was first determined and five cosolvent systems were constructed to fulfill this DEC. Micellar solubilization was achieved by incorporating surfactants of different types (anionic, cationic and non-ionic) in the solvent systems. Softgels were filled with the drug solutions and subjected to in vitro and in vivo studies. Results:Dissolution tests (under sink or non-sink conditions) revealed a correlation between the composition of the softgel core fill liquid and drug dissolution parameters. The incorporation of water in the fill formula as well as the use of ingredients with low hygroscopicity was found to be essential to minimize water migration to the fill liquid during storage. In vivo studies showed rapid and enhanced absorption of felodipine from solubilized core softgels compared with control drug powder filled in hard gelatin capsules. The total amount of drug absorbed over a 24-h period was markedly enhanced (1.6-fold) for softgels compared with control capsules. Conclusions:It was concluded that the formulation of felodipine in soubilized-core softgels enhanced the rate and extent of dissolution of this insoluble drug. In addition, the drug absorption was increased leading to improved bioavailability.


Keywords:  Felodipine   Softgels   Dielectric constant   Micellar solubilization   Bioavailability