Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules

Mary-Carmel Kearney, Peter E. McKenna, Helen L. Quinn, Aaron J. Courtenay, Eneko Larraneta, Ryan F. Donnelly

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Abstract

The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P > 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% ± 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds.
Original languageEnglish
JournalPharmaceutics
Volume11
Issue number605
DOIs
Publication statusPublished - 13 Nov 2019

Keywords

  • poorly soluble
  • hydrophobic
  • microneedles
  • transdermal
  • Nile red
  • atorvastatin
  • olanzapine
  • Franz cell

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