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Title: Evaluation of calcium alginate beads as a prolonged release delivery system for an orally active iron chelator
Authors: Zastre, Jason A.
Issue Date: 1-Nov-1997
Abstract: Cooley's anemia or $\beta$-thalassemia major affects over 100,000 newborns yearly. Treatment involves blood transfusions every 2-4 weeks for the rest of their life. This therapy leads to extreme iron overload resulting. Current therapy for iron overload requires s.c. or i.v. infusions of an iron chelator for 8-12 h per day up to six times a week, causing many patients to be noncompliant. An orally active iron chelator 1,2-Dimethyl-3-Hydroxypyrid-4-one (DMHP) has been developed but the short half life means dosing several times per day. Encapsulation DMHP iron chelator utilizing calcium alginate beads to facilitate prolonged release was investigated. Beads were produced by dripping a sodium alginate solution containing 15 mg/mL DMHP into a curing solution of 4% CaCl$\sb2$, and curing. Beads were then tray dried for 24 h. Dissolution tests were done using the basket method over 6 h. in pH = 2.0 HCl-KCl buffer and pH = 7.4 phosphate buffer. Beads tested in pH = 2.0 buffer did not swell or rehydrate. Complete release of DMHP was obtained within 45-60 min facilitated by diffusion of DMHP through the pores and cracks of the bead structure. Release in pH = 7.4 media was prolonged due to swelling and slow erosion of the beads. An immediate release phase was evident within the first 15 min. followed by a sigmodial shaped phase. Additives such as PMC, propylene glycol, and pectin were included to control the rapid release in pH = 2.0 medium, but none delayed the release rate. In pH 7.4 buffer, calcium alginatepectin beads conformed to the zero order release model. Therefore the beads would have to be enteric coated to prevent quick release in the acidic environment of the stomach and to allow a prolonged release in the intestine. (Abstract shortened by UMI.)
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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