Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management

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.

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Materials

Risperidone (99.8 %) was purchased from Cangzhou Enke Pharma-tech Co., Ltd (Hebei Province, China). We got PVP K-90 (MW 1,300 kDa) and Plasdone™ K-29/32 (PVP MW 58 kDa) from Ashland (Kidderminster, UK). Elga PURELAB DV 25 purification system, (Veolia Water Systems, Dublin, Ireland) was used for ultrapure water supply. The remaining materials were obtained from Fisher Scientific (Loughborough, UK) or Sigma-Aldrich (Dorset, UK) and were of analytical grade. Full-thickness neonatal porcine skins were obtained from stillborn piglets within 24 h post-mortem and stored at − 20 °C until use.

Rand Ghanma, Yara A. 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, Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management, International Journal of Pharmaceutics, Volume 660, 2024, 124342, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124342.

Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management

Materials

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