Dissertation/Thesis Abstract

Development and Characterization of Chitosan Crosslinked with Tripolyphosphate as a Sustained Release Agent in Tablets
by Pinto, Colin Andrew, Ph.D., University of the Sciences in Philadelphia, 2017, 239; 10692987
Abstract (Summary)

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.

Indexing (document details)
Advisor: Neau, Steven H.
Commitee: Gupta, Pardeep K., Howard, Matthew A., Schaefer, Frederick T.
School: University of the Sciences in Philadelphia
Department: Pharmaceutics
School Location: United States -- Pennsylvania
Source: DAI-B 79/04(E), Dissertation Abstracts International
Subjects: Pharmaceutical sciences
Keywords: Chitosan tripolyphosphate, Compression, Design of experiments, Dissolution, Dynamic vapor sorption analysis, Ionic crosslinking, Sustained-release, Tablets
Publication Number: 10692987
ISBN: 978-0-355-41471-4
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