Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs

J Pharm Sci. 2015 Oct;104(10):3490-500. doi: 10.1002/jps.24563. Epub 2015 Jul 6.

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.

Keywords: HPLC; dissolution; formulation; mechanical properties; permeability; polymeric drug delivery systems; skin; transdermal drug delivery.

MeSH terms

  • Administration, Cutaneous*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
  • Animals
  • Animals, Newborn
  • Aspirin / administration & dosage
  • Aspirin / pharmacokinetics
  • Atorvastatin / administration & dosage
  • Atorvastatin / pharmacokinetics
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / pharmacokinetics
  • Chemistry, Pharmaceutical
  • Drug Combinations
  • Drug Delivery Systems
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • In Vitro Techniques
  • Lisinopril / administration & dosage
  • Lisinopril / pharmacokinetics
  • Microinjections
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Swine

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Drug Combinations
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors
  • Atorvastatin
  • Lisinopril
  • Aspirin