Polymeric microneedles for delivery of Risperidone

: pharmaceutics, pharmaceutical analysis, nanomedicine and pharmacokinetics

Abstract

Schizophrenia is a psychiatric disorder that results from abnormal levels of neurotransmitters in the brain. One of the common drugs prescribed for the treatment of schizophrenia is risperidone (RIS). This drug is a hydrophobic drug that is typically administered orally or intramuscularly. When taken orally, the drug is subjected to first-pass metabolism and enzymatic degradation in the gastrointestinal tract and it requires frequent dosing. Moreover, intramuscular (IM) injections are associated with pain and discomfort. Transdermal drug delivery (TDD) could potentially improve the delivery of RIS. Therefore, this thesis explores a novel approach involving the use of dissolving and hydrogel-forming microneedle array patches (MAPs) for the delivery of RIS. Nanocrystals (NCs) were developed and formulated into dissolving MAPs (DMAPs). Furthermore, directly compressed tablets (DCTs) were prepared from RIS and cyclodextrins (CDs) and combined with hydrogel-forming MAPs (HFMAPs) that were cast using different types of polymers and crosslinking processes. MAPs were evaluated for their insertion efficiency, mechanical properties and ex vivo drug permeation and skin deposition using neonatal porcine skin. Based on the results, the lead DMAPs and HFMAPs with DCTs were selected for further investigation through in vivo pharmacokinetics studies using Sprague Dawley rats. Both RIS and its active metabolite 9-hydroxy risperidone (9-OH-RIS) were evaluated. The result had shown, for the first time, the delivery of RIS transdermally via DMAPs for five days. HFMAPs were applied into two groups of rats one having the MAPs for one day and the other having the patch for five days. It was seen that the prolonged wear of the patches extended the release up to ten days compared to five days with one-day application. Consequently, this thesis offers substantial evidence to support the broader application of MAPs for the transdermal delivery of poorly water soluble drugs.

Thesis is embargoed until 31 December 2028.

Date of Award	Dec 2023
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Jordan University of Science and Technology
Supervisor	Ryan Donnelly (Supervisor) & Alejandro Paredes (Supervisor)