Characterisation of polylactide microspheres.

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 pm). 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. Abbreviations ACL Op Op’ Op” D(v, 0.1) D (V, 0.5) D (V, 0.9) Da DSC e EPBS FTIR GA GPC h I lo lA IV IM K Kda In M M Mi MMD MTDSC Mr, Anterior cruciate ligament Heat capacity In phase component Out phase component Diameter below which 10% of the volume of particles lie Volume median diameter Diameter below which 90% of the volume of particles lie Daltons Differential scanning calorimetry Extinction Coefficient Ethanol: phosphate buffered solution Fourier transform infrared spectroscopy Glycolic acid Gel permeation chromatography Planck’s constant Intensity transmitted Intensity Incident Intraarterial Intravenous Intramuscular Rate Kilo Daltons Natural logarithm Mass Unreleased entrapped drug Molecular weight Metastable molecular dispersion Modulated temperature differential scanning calorimetry Number average molecular weight Mv Mw n Hi [n] p PBS PD PDA PDLA PGA PLA PLGA PLLA PLLALL PVA 80 SD SEM SS t Tg Tgi Tg2 TG TGA TgD TgH THF Tm uv Viscosity average molecular weight Weight average molecular weight Mean Number of moles Intrinsic viscosity Momentum Phosphate buffered solution Polydispersity Poly d, lactide Poly d, I -lactide Poly glycolic acid Polylactide Polylactide co glycolide Poly l-lactide Poly I lactic acid co I lysine Poly vinyl alcohol Subcutaneous Standard deviation Scanning electron microscopy Solid solution Time Glass transition temperature Glass transition temperature of fast cooled system Glass transition temperature of slow cooled system Thermogravimetry Thermogravimetric analysis Dehydrated glass transition temperature Hydrated glass transition temperature Tetrahydrafuran Melt transition temperature Ultraviolet V Volts VMD Volume median diameter X Wavelength Wj Weight of the î ̂monomer unit XRD X-ray diffraction XRPD X ray powder diffraction