The ability of chitosan and tripolyphosphate to form an ionic crosslinked material and its effectiveness in sustained release formulations has been reported. However, key issues commonly observed with these formulations include inefficiencies and inaccuracies in the drug loading as well as an inability to achieve complete release of drug. Acetaminophen, as a model drug, was added to various chitosan-tripolyphosphate crosslinked powders to assess the sustained release characteristics when drug is added extragranularly as opposed to during the crosslinking process, which is the most common procedure for drug addition in prior literature. The influence of various process and formulation variables including chitosan concentration, chitosan:tripolyphosphate ratio, temperature, ionic strength, and pH was assessed. Design of experiments allowed the identification of factors and two factor interactions that have significant effects on particle size and size distribution, yield, zeta potential, true density, and drug release. Statistical model equations were successfully used to manufacture optimized chitosan-tripolyphosphate crosslinked powders with various properties for further evaluation. Analysis of the compressibility of the optimized powders revealed that the crosslinked powders had enhanced compression properties when compared to chitosan powder. Environmental scanning electron microscopy revealed a correlation between the rigidity and density of the powders and corresponding capabilities for enhanced sustained release. Analysis of the moisture sorption and desorption isotherms from dynamic vapor sorption analysis revealed various types and levels of water present and a correlation between the quantity of water internally absorbed during sorption and desorption and sustained release capability. Chitosan-tripolyphosphate crosslinked powder can be manufactured with optimized properties that allow desired sustained drug release profiles while simultaneously serving as the primary diluent for solid oral dosage forms.
|Advisor:||Neau, Steven H.|
|Commitee:||Gupta, Pardeep K., Howard, Matthew A., Schaefer, Frederick T.|
|School:||University of the Sciences in Philadelphia|
|School Location:||United States -- Pennsylvania|
|Source:||DAI-B 79/04(E), Dissertation Abstracts International|
|Keywords:||Chitosan tripolyphosphate, Compression, Design of experiments, Dissolution, Dynamic vapor sorption analysis, Ionic crosslinking, Sustained-release, Tablets|
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