Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management

Rand Ghanma, Yara Naser, Qonita Kurnia Anjani, Akmal Hidayat Bin Sabri, Aaron R.J. Hutton, Lalitkumar K. Vora, Achmad Himawan, Natalia Moreno-Castellanos, Brett Greer, Helen O. McCarthy, Alejandro J. Paredes, Ryan F. Donnelly

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Abstract

Schizophrenia is a psychiatric disorder that results from abnormal levels of neurotransmitters in the brain. Risperidone (RIS) is a common drug prescribed for the treatment of schizophrenia. RIS is a hydrophobic drug that is typically administered orally or intramuscularly. Transdermal drug delivery (TDD) could potentially improve the delivery of RIS. This study focused on the development of RIS nanocrystals (NCs), for the first time, which were incorporated into dissolving microneedle array patches (DMAPs) to facilitate the drug delivery of RIS. RIS NCs were formulated via wet-media milling technique using poly(vinylalcohol) (PVA) as a stabiliser. NCs with particle size of 300 nm were produced and showed an enhanced release profile up to 80 % over 28 days. Ex vivo results showed that 1.16 ± 0.04 mg of RIS was delivered to both the receiver compartment and full-thickness skin from NCs loaded DMAPs compared to 0.75 ± 0.07 mg from bulk RIS DMAPs. In an in vivo study conducted using female Sprague Dawley rats, both RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) were detected in plasma samples for 5 days. In comparison with the oral group, DMAPs improved the overall pharmacokinetic profile in plasma with a ∼ 15 folds higher area under the curve (AUC) value. This work has represented the novel delivery of the antipsychotic drug, RIS, through microneedles. It also offers substantial evidence to support the broader application of MAPs for the transdermal delivery of poorly water-soluble drugs.
Original languageEnglish
Article number124342
JournalInternational journal of pharmaceutics
Volume660
Early online date15 Jun 2024
DOIs
Publication statusPublished (in print/issue) - 20 Jul 2024

Bibliographical note

Publisher Copyright:
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Keywords

  • Dissolving microneedle array patches
  • Nanocrystals
  • Transdermal drug delivery
  • Risperiodone
  • 9-hydroxyrisperidone
  • Polyvinyl alcohol (PVA)
  • Polyvinylpyrrolidone (PVP)
  • Poloxomer P188
  • P407
  • Sodium lauryl sulphate
  • Sodium lauryl sulfate (SLS)
  • Risperidone

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