title: An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres. III. The use of DSC and HSDSC as means of characterising the interaction of the microspheres with buffered media.
abstract: Stearic acid coated cefuroxime axetil (SACA) microspheres have been studied using differential scanning calorimetry (DSC) and high sensitivity DSC (HSDSC) in order to examine the interaction between the spheres and a range of buffer systems, with a view to further enhance the understanding of the mechanism of drug release developed in earlier studies [Robson et al., 1999, 2000]. DSC studies indicated that after immersion in Sorensens modified phosphate buffer (SMPB) pH 5.9 followed by washing and drying, no change in the thermal properties of the spheres was detected up to 60 min of immersion, with a single endotherm noted at circa 56 degrees C, that corresponded to the melting of the stearic acid used in this study; similar results were obtained for systems immersed in distilled water. After immersion in SMPB pH 7.0 and 8.0, however, a second peak was noted at approximately 67 degrees C that increased in magnitude relative to the lower temperature endotherm with increasing exposure time to the medium. Spheres that had not been previously washed prior to drying showed complete conversion to the higher temperature endotherm for these two buffers. Systems which had been exposed to a range of pH 7.0 buffers (citrate-phosphate buffer (CPB), phosphate buffer mixed (PBM), boric acid buffer (BAB)) were then examined. Only the CPB systems showed evidence for conversion to the higher melting form. PBM systems to which further sodium had been added were then examined. A maximum conversion was found at 0.05 M sodium, which was in agreement with the maximum in release rate found in a previous study [Robson et al., 2000]. HSDSC was then used to examine systems that were immersed in the buffer. For SMPB, pH 5.9 and distilled water, only the endotherm corresponding to the stearic acid melting was seen. However, for SMPB pH 7.0 and 8.0, three peaks were seen, two corresponding to those seen for the DSC studies and a further lower temperature peak at circa 44 degrees C. Studies on PBM systems to which additional sodium had been added showed small levels of conversion to the higher temperature form at higher sodium contents. The data was discussed in terms of the correlation with earlier dissolution studies on the same systems [Robson et al., 1999; 2000].
authors.affiliation: Centre for Materials Science, The School of Pharmacy, 29-39 Brunswick Square, WC1N 1AX, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Robson
authors.forename: D Q
authors.initials: DQ
authors.lastname: Craig
authors.forename: D
authors.initials: D
authors.lastname: Deutsch
mesh_terms: D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002444:Cefuroxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D002511:Cephalosporins / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013649:Taste; D013816:Thermodynamics
chemical_list: D002021:Buffers; D002511:Cephalosporins; D003692:Delayed-Action Preparations; D011355:Prodrugs; D013229:Stearic Acids; C031183:stearic acid; D002444:Cefuroxime; C040738:cefuroxime axetil