| Summary: | 碩士 === 臺北醫學大學 === 藥學系 === 94 === The objective of this study was to develop a drug delivery system by in-situ formation of orifice via osmotic pressure activated swelling. This system consisted of a controlling membrane coated tablets containing osmogent and swellable agents. Doxazosin mesylate selected as a model drug were prepared by direct compression with anhydrous lactose and different viscosity grades of hydroxypropyl methylcellulose. Ethylcellulose plasticized by Pharmacoat 606 were applied as the semi-permeable outer coat. Drug release behaviors were investigated by dissolution test using the CHPⅤ apparatusⅡ at rotation speed of 75, 100, and 150rpm in four media of pH 1.2, pH 6.8 buffer, distilled water and NaCl solution. Pilot studies of in vivo pharmacokinetic were conducted as well for comparison with in vitro results. Water uptake was measured to further elucidate the mechanism of drug release. Mechanical properties and construction of films with varying compositions were observed by dynamic mechanical analyzer and scanning electron microscopy.
The results showed that controlling membrane was ruptured by osmotic pressure to activate drug release with a delay time. The lag time was not influenced by pH value of release medium and rotation speeds. The lag time increased with a higher coating level, but decreased with the addition of hydrophilic pore former, Pharmacoat 606, and water amount in coating solution. The lag time also increased with the higher concentration of NaCl in the medium. The results of dissolution study under higher rotation speeds and NaCl solution were found to correlate well with in vivo performance revealed by those in vivo pilot studies. The rates of water uptake increased with higher water amount in coating solution and would be affected by the characteristics of hydroxypropyl methylcellulose in the core tablets. Addition of Pharmacoat 606 and water amount to the coating solution reduced the mechanical properties of films and increased the porosity in membranes.
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