The solubility of non cross-linked chitosan in weak acid solutions restricts its utility in microspheres for drug delivery. The primary aim of this study was to produce pentasodium tripolyphosphate cross-linked chitosan microspheres with higher acid resistance for controlled release of ampicillin. The microspheres were prepared by two different microencapsulation procedures (by emulsification and by spray-drying) and characterized by their particle size, surface morphology, stability, drug entrapment efficiency and drug release. The size of the microspheres was <10 microm with a narrow size distribution. The entrapment of ampicillin in the microspheres was more than 80%. Stability of uncross-linked and cross-linked microspheres was affected by the pH of simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5). The inclusion of the enzymes pepsin and pancreatin did not affect the stability of the microspheres. The inclusion of lysozyme in phosphate buffer saline resulted in increased solubilization. The release of the drug was affected by cross-linking of microspheres with tripolyphosphate (TPP). The cross-linked microspheres were more stable in simulated gastric fluid and showed slower but sustained release of ampicillin. The antimicrobial activity of the released ampicillin was confirmed by Staphylococcus aureus bioassay.
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