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Buffer controlled release of indomethacin from ethylcellulose microcapsules
Affiliation:1. Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, 4th Floor, Columbus, OH 43210 (M.S.M., J.B., A.R.);2. Department of Radiation Oncology, The Ohio State University Medical Center, Columbus, Ohio (E.D.M., D.A.D.);1. Div. of Pharmaceutical Technology, Dept. of Chemistry, University of Hamburg, Bundesstraße 45, 20146 Hamburg, Germany;2. Dept. of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100, Denmark
Abstract:The rate of release of indomethacin from ethylcellulose microcapsules prepared by coacervation was studied using internal buffer, dibasic sodium phosphate (DSP), to increase the solubility of the core. The dissolution rate of the drug was determined in phosphate buffer solutions of varying pH and concentration. The role of the stagnant diffusion layer at the microcapsule surface was also evaluated by changing the mixing in the dissolution test. Indomethacin release was accelerated considerably with increasing amounts of DSP in the core. DSP increases the pH inside the microcapsules, thus enhancing the release of the acidic drug. Increasing bulk solution pH increased the release rate of indomethacin, the enhancing effect being more pronounced with buffered microcapsules. Neither increasing phosphate concentration of the bulk solution nor increasing mixing of the microcapsules influenced the rate of release of indomethacin from unbuffered capsules. With buffered capsules the increase in phosphate concentration of bulk solution prevented leaching out of internal phosphate increasing the release rate of indomethacin. The release of indomethacin also accelerated slightly with increasing mixing.
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