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
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.