Stability assessment of chitosan-sodium hexametaphosphate capsules.
The assessment of the stability of capsules based on chitosan-sodium hexametaphosphate complex formation has been carried out using two independent methods--compression and osmotic swelling, and the influence of the preparation variables was evaluated. The formulation containing 1.5% core polymer (chitosan) and 1.5% oligophosphate, in the absence of salt or at low ionic strength (0.15% NaCl) was found to provide the best membrane resistance. A higher concentration of cross-linker (2.25%) produced stable capsules only in absence of electrolyte. Mannitol, a porogen added to the preparation solutions, did not affect the stability of the obtained membranes. At elevated polyol (1%) and cross-linker levels (2.25%), and at 0% salt, membranes with decreased elasticity were obtained, having lower compression and osmotic bursting values and lower deformation at the breaking points. A significant influence of salt amount on the capsule stability was also found. This was attributed to changes in the membrane formation process resulting in membranes with different thickness and structure. Membrane compression stability was found to be dependent on the pH of both oligophosphate and chitosan solutions, as well as on the reaction time. The bursting force values decreased for capsule diameters below 1.6 mm. The increased membrane/capsule volume ratio for the small capsules decreased the capsule deformation freedom and caused capsule rupture at low force values. The capsules made at low salt amounts showed very good storage stability over time and at elevated temperatures. The results demonstrated that the capsules could be formulated with controlled properties for various biomedical applications.
Angelova
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Department of Chemistry, Swiss Federal Institute of Technology. nela.anguelova@epfl.ch
Hunkeler
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D002214:Capsules; D002462:Cell Membrane / Q000378:metabolism; D002686:Chitin / Q000031:analogs & derivatives / Q000737:chemistry*; D048271:Chitosan; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008353:Mannitol / Q000737:chemistry* / Q000494:pharmacology; D010710:Phosphates / Q000737:chemistry*; D012492:Salts / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors; D014867:Water / Q000378:metabolism
D002214:Capsules; D003432:Cross-Linking Reagents; D015226:Dinucleoside Phosphates; D004573:Electrolytes; D010710:Phosphates; D012492:Salts; D014867:Water; D002686:Chitin; D008353:Mannitol; D012965:Sodium Chloride; D048271:Chitosan; C009285:sodium polymetaphosphate