Super-swelling hydrogel-forming microneedle based transdermal drug delivery: Mathematical modelling, simulation and experimental validation

• Published in: International journal of pharmaceutics Vol. 622; p. 121835
• Main Authors: Ranjan Yadav, Prateek, Iqbal Nasiri, Muhammad, Vora, Lalitkumar K., Larrañeta, Eneko, Donnelly, Ryan F., Pattanayek, Sudip K., Bhusan Das, Diganta
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25-06-2022
• Subjects: Drug retention; Hygroscopy; Mathematical modelling; Super-swelling; Transdermal drug delivery; Super-swelling; Transdermal drug delivery; Hygroscopy; Mathematical modelling; Drug retention
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.121835

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•Drug diffusion is coupled with matrix deformation to study effect of MN swelling and skin viscoelasticity.•The model incorporates drug solubility and drug binding with the matrix.•MN experiences upward force due to skin viscoelasticity that resists swelling.•Controlled release is achieved by tuning MN swelling and reservoir properties.
Super-swelling hydrogel-forming microneedles (HFMNs) based transdermal drug delivery (TDD) is gaining significant interest due to their non-invasiveness and ability to deliver a wide range of drugs. The HFMNs swell by imbibing interstitial skin fluid (ISF), and they facilitate drug transport from the reservoir attached at the base into the skin without polymer dissolution. To develop HFMNs for practical applications, a complete understanding of the drug transport mechanism is required, allowing for controlled TDD and geometrical optimisation. A three-phase system consisting of a reservoir, microneedle, and skin is considered. A mathematical model is developed to incorporate the drug binding within the matrix of the compartment, which was not considered earlier. Super-swelling nature of the HFMNs is incorporated through the swelling ratio obtained experimentally for a polymer. The results are validated with in vitro diffusion studies of ibuprofen sodium (IBU) across excised porcine skin, showing that around 20% of the loaded IBU in lyophilised wafer was delivered in 24 h. It was observed that increasing IBU solubility in reservoir can achieve high drug transport across the skin. The developed model is shown to be in good agreement with the experimental data. It is concluded that the proposed model can be considered a tool with predictive design and development of super-swelling HFMNs based TDD systems.