Membrane emulsification for particle production

• Main Author: Gasparini, Gilda
• Published: Loughborough University 2008
• Subjects: 615.19
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510297

The main aim of this research is to investigate a novel emulsification device and its application to the production of biodegradable particles for controlled release drug encapsulation. The emulsification method chosen was a non crossflow membrane technique. The membrane is a flat thin layer with very regular array of pores and it is treated to produce oil-in-water or water-in-oil emulsions. Initially, a range of tests were conducted in order to link the operating conditions with the droplet size and size distribution. For this part a simple system of sunflower oil in water was used. Applied shear, injection rate, pore size and pore distance all had an effect on the resulting droplets. Sometimes these factors are not independent from each other leading to different overall effects. A model based on the force balance was proposed. lt includes the Capillary force acting against the Drag Force and a novel Push-off force originated by the interaction of neighbouring droplets in the absence of coalescence. The knowledge of the system was then applied to particle production. There is the requirement of a production method for very uniform particles with a diameter ranging between 50 and 100 μm to be used for subcutaneous (under the skin) administrations. The main benefit of making uniform particles is that it enables the engineering (i.e. mixing) of the monosized particles to give the required size distribution hence the required release pattern. The particles were produced by membrane emulsification followed by solvent evaporation. lt was of interest to encapsulate a water soluble drug, as it is more challenging to maintain high encapsulation efficiency in this case. Hence a double emulsification, W/O/W was performed. lt is shown that by changing the operating conditions it is possible to vary the size and size distribution, while by controlling the solvent evaporation rate it is possible to optimize the encapsulation efficiency. Particles of exactly 50 and 100 μm in diameter were produced, with a best span of 0.29 and encapsulation efficiency as high as 100% when encapsulating a hydrophilic. The obtained particles were used to study the release of a model hydrophilic drug and the changes in size and size morphology were followed over time too. Previously, PLGA was believed to undergo bulk erosion due to hydrolysis once in body-like conditions. The data gathered regarding the changes in size suggests that together with bulk erosion, when a hydrophilic phase is present inside the particles, surface erosion takes place too. A model for the release has been proposed based on diffusion and considering the variation in size of the particles.