title: Production of dissolvable microneedles using an atomised spray process: effect of microneedle composition on skin penetration.
abstract: Dissolvable microneedles offer an attractive delivery system for transdermal drug and vaccine delivery. They are most commonly formed by filling a microneedle mold with liquid formulation using vacuum or centrifugation to overcome the constraints of surface tension and solution viscosity. Here, we demonstrate a novel microneedle fabrication method employing an atomised spray technique that minimises the effects of the liquid surface tension and viscosity when filling molds. This spray method was successfully used to fabricate dissolvable microneedles (DMN) from a wide range of sugars (trehalose, fructose and raffinose) and polymeric materials (polyvinyl alcohol, polyvinylpyrrolidone, carboxymethylcellulose, hydroxypropylmethylcellulose and sodium alginate). Fabrication by spraying produced microneedles with amorphous content using single sugar compositions. These microneedles displayed sharp tips and had complete fidelity to the master silicon template. Using a method to quantify the consistency of DMN penetration into different skin layers, we demonstrate that the material of construction significantly influenced the extent of skin penetration. We demonstrate that this spraying method can be adapted to produce novel laminate-layered as well as horizontally-layered DMN arrays. To our knowledge, this is the first report documenting the use of an atomising spray, at ambient, mild processing conditions, to create dissolvable microneedle arrays that can possess novel, laminate layering.
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland. Electronic address: marie_mc_grath@hotmail.com.
authors.forename: Marie G
authors.initials: MG
authors.lastname: McGrath
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland. Electronic address: svucen@ucc.ie.
authors.forename: Sonja
authors.initials: S
authors.lastname: Vucen
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland. Electronic address: avrdoljak@gmail.com.
authors.forename: Anto
authors.initials: A
authors.lastname: Vrdoljak
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland. Electronic address: 109427716@umail.ucc.ie.
authors.forename: Adam
authors.initials: A
authors.lastname: Kelly
authors.affiliation: Tyndall National Institute, University College Cork, Cork, Ireland. Electronic address: conor.omahony@tyndall.ie.
authors.forename: Conor
authors.initials: C
authors.lastname: O'Mahony
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
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland; Dept. of Pharmacology, University College Cork, Cork, Ireland. Electronic address: anne.moore@ucc.ie.
authors.forename: Anne
authors.initials: A
authors.lastname: Moore
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D004867:Equipment Design / Q000295:instrumentation / Q000379:methods; D008845:Microinjections / Q000295:instrumentation* / Q000379:methods*; D009330:Nebulizers and Vaporizers; D009339:Needles; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012996:Solutions / Q000737:chemistry; D013552:Swine; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
chemical_list: D011108:Polymers; D012996:Solutions; D011142:Polyvinyl Alcohol; D002266:Carboxymethylcellulose Sodium
keywords: Amorphous sugars; Atomising spray; Dissolving microneedles; Skin; Transdermal drug delivery