title: Dissolvable microneedle fabrication using piezoelectric dispensing technology.
abstract: 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.
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Evin A
authors.initials: EA
authors.lastname: Allen
authors.affiliation: Tyndall National Institute, Lee Maltings, University College Cork, Cork, Ireland.
authors.forename: Conor
authors.initials: C
authors.lastname: O'Mahony
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Cronin
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Mahony
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland; Dept. of Pharmacology, University College Cork, Cork, Ireland.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland. Electronic address: a.crean@ucc.ie.
authors.forename: Abina M
authors.initials: AM
authors.lastname: Crean
mesh_terms: D016503:Drug Delivery Systems; D004867:Equipment Design; D007252:Influenza Vaccines; D009339:Needles; D012995:Solubility; D013678:Technology, Pharmaceutical
chemical_list: D007252:Influenza Vaccines
keywords: Bilayer; Influenza vaccine; Microneedle; Ohnesorge number; Piezoelectric dispensing; Vaccine delivery