Dissolvable microneedle fabrication using piezoelectric dispensing technology.

Dissolvable microneedle (DMN) patches are novel dosage forms for the percutaneous delivery of vaccines. DMN are routinely fabricated by dispensing liquid formulations into microneedle-shaped moulds. The liquid formulation within the mould is then dried to create dissolvable vaccine-loaded microneedles. The precision of the dispensing process is critical to the control of formulation volume loaded into each dissolvable microneedle structure. The dispensing process employed must maintain vaccine integrity. Wetting of mould surfaces by the dispensed formulation is also an important consideration for the fabrication of sharp-tipped DMN. Sharp-tipped DMN are essential for ease of percutaneous administration. In this paper, we demonstrate the ability of a piezoelectric dispensing system to dispense picolitre formulation volumes into PDMS moulds enabling the fabrication of bilayer DMN. The influence of formulation components (trehalose and polyvinyl alcohol (PVA) content) and piezoelectric actuation parameters (voltage, frequency and back pressure) on drop formation is described. The biological integrity of a seasonal influenza vaccine following dispensing was investigated and maintained voltage settings of 30 V but undermined at higher settings, 50 and 80 V. The results demonstrate the capability of piezoelectric dispensing technology to precisely fabricate bilayer DMN. They also highlight the importance of identifying formulation and actuation parameters to ensure controlled droplet formulation and vaccine stabilisation.

Alkylthiol gold nanoparticles in open-tubular capillary electrochromatography.

Open-tubular columns for capillary electrochromatography (CEC) were formed by immobilising dodecanethiol gold nanoparticles on prederivatised 3-aminopropyl-trimethoxysilane (APTMS) or 3-mercaptopropyl-trimethoxysilane (MPTMS) fused-silica capillaries. The initial stage of this research involved the synthesis and characterisation of dodecanethiol gold nanoparticles, with tunnelling electron microscopy analysis of the dispersed phase of the gold nanoparticles dispersion in CHCl3, revealing spherical particles. The surface features of an Au-MPTMS coated capillary column were determined using scanning electron microscopy. The electroosmotic flow characteristics of Au-APTMS and Au-MPTMS capillary columns were then determined, by varying the pH and the voltage. The electrochromatographic properties of the gold nanoparticles CEC capillaries were investigated using a "reversed-phase" test mixture of thiourea, benzophenone and biphenyl and selected pyrethroid pesticides. Efficient separations of benzophenone and biphenyl solutes on Au-MPTMS and Au-APTMS capillary columns were obtained, as were linear plots of logarithm capacity factor versus % MeOH. A study of the reproducibility of retention for these solutes on Au-APTMS, Au-MPTMS and on a loosely coated capillary demonstrated the necessity of a coupling agent to prevent the gold nanoparticles from washing-off. These dodecanethiol gold capillary columns are easier to produce and operate than packed capillary columns. The research work confirms the use of gold nanoparticles as a novel phase for open-tubular CEC, demonstrating reproducible retention and characteristic reversed-phase behaviour.