Needle-free drug and vaccine delivery devices have been developed by the Department of Engineering Science at The University of Oxford in collaboration with PowderJect Pharmaceuticals plc. In them, micro-particles of pharmaceuticai agent are accelerated, by a supersonic flow of gas in a nozzle, to velocities sufficient for them to penetrate the outer layers of the skin. If the gas flow is over-expanded relative to the atmosphere to which it discharges, shock waves form inside the nozzle, which cause the flow to separate from the wall. The resulting gas-particle flow field is highly non-uniform, leading to suboptimal drug or vaccine delivery and even damage to the target skin.

Vaccination remains the most important approach to offering protection from infectious diseases. However, using needles and syringes for vaccine administration continues to be a matter of concern, especially in developing countries. Re-use of needles, needle stick injuries and improper disposal of needles in these regions of the world increase the risk of spreading blood-borne pathogens among health care workers, patients and the wider community. The concerns about the safe vaccination practice have led to an intensive effort to develop safe delivery methods for vaccines and replace hypodermic injections. The opportunity to develop a safe and effective method of vaccination using a minimally invasive method is becoming real. The most promising approaches is microneedle (MN) array which has proven to be a safe and cost effective method for vaccination. The current thesis was focus on dissolvable MNs fabricated from 20%w/w poly(methyl vinyl ether/maleic acid) loaded with a model antigen, ovalbumin (OVA). Various experiments were carried out during this thesis to investigate the feasibility and efficacy of using MNs for vaccine delivery. The in vitro studies showed that MNs loaded with OVA were strong enough to avoid breaking under high compression force. The integrity of the primary and secondary structure of OVA loaded into MN arrays successfully ensured. Further, MNs enhanced the release of OVA into the skin compared to passive permeation. In in vivo studies, the OVA released from the MNs' matrix upon insertion into mouse skin targeted dendrite cells (DCs). This thesis showed that av A was engulfed by DCs, processed and migrated to the lymph nodes. Consequently, the processed antigen encountered naive T cells, which led to initiation of robust humoral and cellular immune responses indicated by production of IgG, IgG 1, IgG2a, IFN-γ and IL-4. Interestingly, the PMVE/MA copolymer used to fabricate MNs seems to have adjuvant effects, indicated by the higher IgG level of mice immunized using MNs fabricated from PMVE/MA loaded with OVA compared with MNs fabricated from PMVE/MA and loaded with OVA plus adjuvant imiquimod.

The research resulted in the development of wax matrix pellet systems using a direct warm spheronisation method for use as sustained release devices in oral drug delivery. The effect of altering process parameters on resultant pellet morphology, size distribution and in vitro dissolution performance was evaluated. Changes in the physicochemical and morphological properties of glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) used in pellet formulations following ageing were monitored by use of FT-IR spectrophotometry, differential scanning calorimetry, hot stage microscopy, X-ray powder diffraction, texture analyses, polarised light microscopy, scanning electron microscopy and dissolution testing. Use of the direct warm spheronisation process resulted in the production of the unstable α-form of GMS that slowly reverted to the stable β-polymorph upon storage at 25°C but GPS exhibited changes in crystallinity upon storage. Thermal annealing of GMS and GPS formulations at 46°C resulted in the melt-solidified GMS (α-form) more rapidly transforming to the stable β-form whereas melt-solidified GPS crystallised faster when compared to 25°C. The thermal annealing cycle at 46°C caused divergent effects in GMS and GPS pellet formulation dissolution performance with decreased drug release rates observed for GMS pellet formulations and increased drug release rates observed for GPS pellet formulations. Moreover, dissolution performance of pellet formulations after annealing was dependent on both wax and drug composition. The inclusions of excipients that stabilised the thermal properties of wax were only effective in preventing modification in pellet dissolution performance for short periods (2 weeks) post-annealing. The combined use of excipients and thermal annealing to stabilise the properties of waxes and provide consistent performance of the delivery device requires further optimisation before it can be a truly useful application for the industrial manufacture of pharmaceutical wax-based oral delivery devices.

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Poorly water-soluble drugs with limited absorption in the gastrointestinal tract commonly show increased bioavailability when drug dissolution is improved by conversion to the amorphous form or a reduction in particle size. In this study, different polymer matrices were employed to convert model drugs into the amorphous state.

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