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An investigation into the mechanisms of drug release from stearic acid coated cefuroxime axetil (SACA)

Robson, Hazel Jane; (1998) An investigation into the mechanisms of drug release from stearic acid coated cefuroxime axetil (SACA). Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Stearic acid coated cefuroxime axetil (SACA) is an intermediate product in the production of cefuroxime axetil for oral suspension (CAOS). The inclusion of stearic acid within the formulation provides a means of successfully masking the bitter taste of the drug. This is an extremely important issue as the formulation is intended for administration to young children. This study has been performed in order to gain an insight into the mechanism by which cefuroxime axetil is released from SACA. As the manufacturing process is relatively simplistic a long term aim is the application of this technology to taste mask other unpleasant tasting compounds. Initial dissolution studies were carried out to investigate the effect of pH and buffer composition on the overall level of drug release. Optimal drug levels were obtained using a phosphate buffer (Sorensens modified phosphate buffer) made up to a pH of 7.0. The addition of sodium, in the form of sodium chloride, also had a profound effect on the level of drug release obtained. Increasing the sodium levels of a second phosphate buffer (phosphate mixed, (Na+, 0.007M), dramatically increased the level of drug release up to a molarity of 0.05 after which a steady decrease was observed. Following on from the dissolution studies scanning electron microscopy (SEM) was used to investigate the surface morphology of the material during dissolution in a range of media. A method was developed in which SACA was removed at particular time points and dried. Changes were seen to have taken place on the surface of spheres after dissolution in particular buffers, notably the ones which produced the higher levels of drug release. These changes were seen to be time dependent and were exaggerated when the material was suspended in the media during the drying process. Thermal studies were carried out using differential scanning calorimetry (DSC) and high sensitivity differential scanning calorimetry (HSDSC). DSC examination of dried material, which had undergone dissolution in buffers which had produced optimal levels of drug release, showed a second peak to be present indicating that a second component with a different melting point to that of SACA was present. For examination by HSDSC dry SACA was heated in a range of buffers. Multiple peaks were observed in media which were known to produce optimal drug release, but not in media which resulted in sub-optimal drug release, confirming that an interaction did indeed occur between SACA and certain buffers. Flame photometry, X-ray diffraction and gas chromatography were used as supportive techniques and confirmed the generation of a novel species after exposure to media in which drug release was maximised. With regards to the mechanism of drug release these results have indicated that it is a complex process comprising of more than one mechanism.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: An investigation into the mechanisms of drug release from stearic acid coated cefuroxime axetil (SACA)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Oral suspensions
URI: https://discovery.ucl.ac.uk/id/eprint/10105047
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