C Ramkissoon-Ganorkar1, A Gutowska, F Liu, M Baudys, S W Kim. 1. Department of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City 84112, USA.
Abstract
PURPOSE: To study the physical and release properties of different molecular weight (MW) pH- and temperature-responsive statistical terpolymers and beads of N-isopropylacrylamide (NIPAAm), butylmethacrylate (BMA) and acrylic acid (AA). METHODS: Random terpolymers of varying MW were synthesized with NIPAAm/BMA/AA of feed mol ratio 85/5/10. Polymeric beads were formed by dropping a polymer solution into an oil bath kept at a temperature above the lower critical solution temperature (LCST) of the polymer. The release profile of cytochrome c was investigated as a function of the polymer MW and pH of the release medium at 37 degrees C. RESULTS: The weight average MW ranged between 49,000 and 3 million. The LCST at pH 2.0 and pH 7.4 was 22 degrees C and 60 degrees C respectively. SEM studies showed that the size of the pores decreased as the MW increased. Irrespective of MW, the polymeric beads did not swell or dissolve at pH 2.0 and 37 degrees C and showed minimal drug release. At pH 7.4 and 37 degrees C, the rate of bead dissolution/swelling decreased as the MW of the polymer increased. CONCLUSIONS: By modulating polymer MW, it was possible to vary the physical properties of beads. Dissolution/swelling characteristics were dependent on the MW of the polymer. Such unique dissolution/swelling properties are useful for delivering drugs to different sites in the intestine.
PURPOSE: To study the physical and release properties of different molecular weight (MW) pH- and temperature-responsive statistical terpolymers and beads of N-isopropylacrylamide (NIPAAm), butylmethacrylate (BMA) and acrylic acid (AA). METHODS: Random terpolymers of varying MW were synthesized with NIPAAm/BMA/AA of feed mol ratio 85/5/10. Polymeric beads were formed by dropping a polymer solution into an oil bath kept at a temperature above the lower critical solution temperature (LCST) of the polymer. The release profile of cytochrome c was investigated as a function of the polymer MW and pH of the release medium at 37 degrees C. RESULTS: The weight average MW ranged between 49,000 and 3 million. The LCST at pH 2.0 and pH 7.4 was 22 degrees C and 60 degrees C respectively. SEM studies showed that the size of the pores decreased as the MW increased. Irrespective of MW, the polymeric beads did not swell or dissolve at pH 2.0 and 37 degrees C and showed minimal drug release. At pH 7.4 and 37 degrees C, the rate of bead dissolution/swelling decreased as the MW of the polymer increased. CONCLUSIONS: By modulating polymer MW, it was possible to vary the physical properties of beads. Dissolution/swelling characteristics were dependent on the MW of the polymer. Such unique dissolution/swelling properties are useful for delivering drugs to different sites in the intestine.