title: Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.
abstract: Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds.
authors.affiliation: School of Pharmacy, Queen's University, Belfast, BT9 7BL, UK.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Quinn
authors.affiliation: School of Pharmacy, Queen's University, Belfast, BT9 7BL, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Bonham
authors.affiliation: School of Pharmacy, Queen's University, Belfast, BT9 7BL, UK.
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Hughes
authors.affiliation: School of Pharmacy, Queen's University, Belfast, BT9 7BL, UK.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
mesh_terms: D000279:Administration, Cutaneous; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000069059:Atorvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D016503:Drug Delivery Systems; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D017706:Lisinopril / Q000008:administration & dosage / Q000493:pharmacokinetics; D008845:Microinjections; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D013552:Swine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D000069059:Atorvastatin; D017706:Lisinopril; D001241:Aspirin
keywords: HPLC; dissolution; formulation; mechanical properties; permeability; polymeric drug delivery systems; skin; transdermal drug delivery