Studies into solid core drug delivery system using haemoglobin as a model drug and supercritical fluid processing for encapsulation

摘要

The aim of this project was to formulate a solid core drug delivery system for oral delivery of proteins using silica as core material, haemoglobin as model drug and supercritical fluid processing as encapsulation technique. Silica particles of different morphology were used as a carrier material for protein immobilisation and fatty acids coating was performed using supercritical carbon dioxide (CO2) as a processing media.ududThe melting behaviour of saturated fatty acids (lauric, myristic, palmitic and stearic acid) and pluronics (F-38, F-68, F-77, F-127 and F-108) were studied under pressurised CO2 to identify the coating parameters. These excipients showed a melting point depression in the range of 10 to 20 °C in pressurised CO2. In the case of fatty acids the decrease in melting point was inversely proportional to the carbon chain length and directly related to the polarity of carbonyl group. Whereas, melting point depression for all pluronics was similar and was attributed to the high cohesive energy density of these polymers. This phenomenon was used to encapsulate the thermolabile protein molecules in pressurised CO2 at low temperatures.ududThe stability of bovine haemoglobin (bHb) was studied by ultraviolet-visible and circular dichroism spectroscopy. Thermal, storage and agitation stability were studied to identify the processing parameters for the storage, adsorption and desorption processes. ududThree morphologically different silica particles were studied as potential inorganic carrier for the protein. The particles were characterised by nitrogen adsorption and scanning electron microscopy and the maximum protein adsorption and kinetics was determined at pH 6. The bHb adsorption on silica was found to be irreversible, hence application of pluronics as a displacer was also studied.ududFinally, the bHb adsorbed particles were coated with fatty acids by supercritical fluid processing and solvent evaporation methods. The highest bHb release was obtained from SFP (Syloid FP-244) silica in comparison to other silica particles in pH 6.8 phosphate buffer. SFP based formulation also showed a trend in the protein release which was dependent on the solubility of fatty acids in the release media. The highest release was obtained from myristic acid coated solid core drug delivery system (SCDDS) followed by palmitic and stearic acid. Lauric acid coated SFP formulations led to changes in protein conformations, hence omitted from these studies. The release studies of myristic acid based SCDDS in simulated gastric and intestinal fluids showed that fatty acid coating provided enteric properties to the formulation. It can be concluded from these studies that SCDDS prepared using mesoporous silica as core and fatty acids as coating material can be an effective drug delivery system for the oral delivery of biomolecules.