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Characterisation of polylactide microspheres

Ikwueme, Stella Ngozichukwu; (2003) Characterisation of polylactide microspheres. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

This thesis describes the preparation of poly-d,l-lactide (PDLA) microspheres by the solvent evaporation method. Laser diffraction particle size analysis showed that the median diameter of the PDLA microspheres produced was relatively small (7-22 μm). The shape of the PDLA microspheres was observed by SEM to be spherical. Upon increasing the drug load within PDLA microspheres, drug particles appeared on the surface of the microspheres. The solvent evaporation process proved to be efficient, as the experimental drug loading was close to the theoretical drug loading, indicating little raw material was lost during microsphere preparation. The release profile of progesterone and estrone from the microspheres was characterised by two release phases; an initial quick burst of drug followed by a slower sustained release. In vitro release kinetics of progesterone and estrone loaded PDLA microspheres were identified as being dependent on the square root of time, indicating release was mainly diffusion controlled, although SEM revealed the release of the compounds from PDLA was also due to surface erosion. Progesterone plasticised PDLA at drug loads of 30% w/w and less, whilst estrone did not show any evidence of plasticisation. At 20% w/w progesterone loading, cold crystallisation of progesterone was observed indicating an amorphous form of the drug was present. Cold crystallisation was not observed for estrone, indicating only a crystalline form of drug was present. PDLA microspheres were evaluated for their in vitro degradation behaviour in ethanol phosphate and phosphate buffers (EPBS and PBS) using gel permeation chromatography (GPC). The mode of degradation of drug free PDLA microspheres incubated in PBS and EPBS were biphasic. GPC results suggest the rate of Mw change of progesterone and estrone PDLA microspheres incubated in EPBS were similar to each other. Therefore, it is deemed changing the drug from progesterone to estrone (and vice versa) had very little effect on the Mw change of PDLA during the 40 days of incubation in EPBS. Overall it was determined that PDLA degradation was homogeneous.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Characterisation of polylactide microspheres
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10106052
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