Journal
DRUG DEVELOPMENT RESEARCH
Volume 64, Issue 2, Pages 114-128Publisher
WILEY-LISS
DOI: 10.1002/ddr.10416
Keywords
chitosan microspheres; spray drying; tripolyphosphate; acetaminophen; swelling; controlled release; release kinetics
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The present study reports on the preparation of chitosan-tripolyphosphate (TPP) microspheres by the spray-drying method using acetaminophen as a model drug substance. Chitosan-TPP microspheres were spherical and had a smooth surface. Perfectly spherical chitosan-TPP microparticles loaded with acetaminophen were obtained in the size range of 3.1-10.1 mu m. Spray-dried chitosan-TPP microspheres were positively charged (zeta potential ranged from +18.4 to +31.8). The encapsulation efficiency of these microspheres was in the range of 48.9-99.5%. The swelling capacity of chitosan-TPP microspheres increased with increases in the molecular weight of chitosan and decreases with increasing volume of 1% wt/vol TPP solution used for the cross-linking reaction. The effect of chitosan concentration, drug loading, volume of TPP solution used for cross-linking, and chitosan molecular weight on surface morphology and drug release rate was extensively investigated. Microparticles with spherical shape and slower release rates were obtained from chitosan-TPP microspheres prepared using a higher concentration of chitosan, higher volume of TPP solution, a higher molecular weight chitosan and/or a higher drug loading. Most importantly, the drug release rate was mainly controlled by the chitosan-TPP matrix density and, thus, by the degree of swelling of the hydrogel matrix. Drug release from chitosan-TPP microspheres occurred via diffusion as the best fit for drug release was obtained using the Higuchi equation. (c) 2005 Wiley-Liss, Inc.
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