Ajiboye, Adejumoke Lara (2018) Studies investigating the preparation of solid core drug delivery systems for oral delivery of y-globulin via supercritical fluid processing technology. PhD thesis, University of Greenwich.

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Abstract

The rising interest in protein therapeutics has led to the growing research in the development of novel carrier systems particularly for oral delivery. However, several physicochemical and biological barriers pose as a challenge for the use of biomolecules as oral drug therapies. Solid core drug delivery systems (SCDDS) allow for immobilization of these molecules on a solid surface to improve and maintain their stability, followed by the enteric coating to achieve targeted/sustained release. Furthermore, supercritical fluid technology (SCFT) as a processing technique may be explored to ensure that the integrity of immobilized molecules is not compromised during the formulation process. The aim of this research was to develop a SCDDS for the oral delivery of peptide/protein-based drugs, using inorganic/organic particles as core, gamma globulin (γ-globulin) as a model drug, fatty acid (FA) as a shell material and SCFT as the processing method.

The adsorption of y-globulin was successfully evaluated with experiments involving particles formulated using polycaprolactone (PCL) and Eudragit® S100 (ES100), and commercially obtained silica known as MSU-H, Syloid AL-1 FP (SAL), Syloid XDP-3150 (SXDP), and Syloid 244 FP (SFP). For silica particles, protein adsorption followed the descending trend of SFP > SXDP > MSU-H >SAL. The variations in adsorbed y-globulin between these particles were largely related to their differences in surface porosity and pore sizes, with minimal effect from a change in pH. On the other hand, electrostatic interactions between the adsorbent surface and the adsorbing molecules were suggested to largely influence y-globulin immobilization on PCL-ES100 systems. SCDDS was successfully formulated by FA coating of protein-adsorbed SFP and SXDP particles (2:1 silica: FA ratio), and MSU-H (1:1 ratio) via melt deposition technique by supercritical carbon-dioxide (scCO2) processing. A pH-induced release of y-globulin was observed with the SCDDS formulations where protein release was not obtained in simulated gastric fluid but achieved in alkaline media.

Item Type:	Thesis (PhD)
Uncontrolled Keywords:	Drug delivery systems; supercritical fluid technology (SCFT);
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science
Last Modified:	08 May 2020 01:38
URI:	http://gala.gre.ac.uk/id/eprint/24775

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