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An investigation into the use of lipid matrices for the controlled release of therapeutic agents

Khan, Nurzalina Abdul Karim; (2000) An investigation into the use of lipid matrices for the controlled release of therapeutic agents. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The variety of components within Gelucires® can result in complex carrier characteristics ranging from polymorphic changes to the interaction of added drugs with the carrier components. Paracetamol, a weakly acidic drug with a pKa of 9.5 and a 1 in 70 solubility in water together with caffeine, a weakly basic drug with a pKa of 13.9 and a 1 in 60 solubility in water, were incorporated into Gelucire 50/13. The effects of the different drugs and their loadings at 5, 10, 20 and 30% w/w were established. Hot-Stage Microscopy (HSM) coupled with a Differential Interference Contrast (DIC) facility and Differential Scanning Calorimetry (DSC) showed that the addition of paracetamol caused a marked change to the matrix by stabilising the lowest melting form of the gelucire whereas caffeine did not significantly affect it. Dissolution studies together with erosion and water uptake studies were performed in distilled water at 37°C. A difference in the contributions of erosion and diffusion as mechanisms of drug release arose due to the different drugs added and mathematical fittings of the results correlated well with physical measurements. The loadings of drug did not greatly affect the parameters studied. The effects of ageing the matrices at 20°C and 37°C after 7, 30, 90 and 180 days storage were also investigated. Storage at the higher temperature tempered the matrices to a more stable form and the drug incorporated also influenced the extent of the ageing effect. Ageing resulted in a lowering of the matrix tensile strength as time progressed and higher drug release rates were obtained during dissolution due to a greater contribution of erosion as the release mechanism. Scanning Electron Microscopy (SEM) studies revealed that the addition of a sterically compatible emulsifier such as sorbitan monostearate inhibited the blooming of stable crystals on the surfaces of the matrices.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: An investigation into the use of lipid matrices for the controlled release of therapeutic agents
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; Lipid; Matrices; Release; Therapeutic
URI: https://discovery.ucl.ac.uk/id/eprint/10105418
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