The present investigation evaluated the potential of coarse particle ethylcellulose (CPEC) and high molecular weight polyethylene oxide (PEO) in the production of beads by an extrusion-spheronization technique. CPEC was investigated as a diluent and PEO as an extrusion aid and a binder. Beads containing CPEC, PEO, and microcrystalline cellulose (MCC) with caffeine as a model drug were manufactured. To compare the effects of particle size of ethylcellulose on properties of the beads, CPEC was substituted with fine particle ethylcellulose (FPEC) in the formulation. Release studies were conducted, and the bead size, shape, yield, and friability were determined. The effects of formulation and process variables and their interactions were studied by a sequential experimental design based on a response surface method. In the initial stage, a two-level, half-fractional factorial design was employed as a screening design, which was subsequently augmented to a central composite design (CCD). Statistical analysis indicated that formulation variables including PEO, MCC, and water content, and two process variables, namely spheronizer speed and spheronization time, significantly affected the properties of the beads. Interactions between two factors have significant effects on several of the measured responses. Simultaneous optimization of the responses was conducted and validated by performing experiments at the optimal conditions. Use of either particle size resulted in beads with acceptable properties. However, CPEC formulations required less water to form a wetted mass suitable for extrusion and showed better tolerance to changes in the water content when compared to FPEC formulations. The friability of the beads produced was less than 2% in either case, although FPEC beads had slightly lower friability values when compared to CPEC beads. Alteration in the drug load from 10% to 70% in the formulation still yielded acceptable product, indicating the suitability of the formulation for a wide range of drug levels. Release profiles showed that there was immediate release of the drug from the beads.
Keywords. Ethylcellulose, polyethylene oxide, extrusion, spheronization, beads, factorial design, response surface method, central composite design, optimization.
|Advisor:||Neau, Steven H.|
|School:||University of the Sciences in Philadelphia|
|School Location:||United States -- Pennsylvania|
|Source:||DAI-B 70/03, Dissertation Abstracts International|
|Subjects:||Pharmacy sciences, Pharmacy sciences|
|Keywords:||Beads, Ethylcellulose, Extrusion-spheronization, Polyethylene oxide|
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