Certain issues with the use of particles of chitosan (Ch) crosslinked with tripolyphosphate (TPP) in sustained release formulations include inefficient drug loading, burst drug release, and incomplete drug release. Acetaminophen was added to Ch:TPP particles to test for advantages to drug addition extragranularly over during crosslinking. The influences of chitosan concentration, Ch:TPP ratio, temperature, ionic strength, and pH were assessed. Design of experiments allowed identification of factors and two factor interactions that have significant effects on average particle size and size distribution, yield, zeta potential, and true density of the particles, as well as drug release from the directly compressed tablets.

 

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