Risperidone-cyclodextrin complex reservoir combined with hydrogel-forming microneedle array patches for enhanced transdermal delivery

Hydrogel-forming microneedle array patches (HFMAPs) are microneedles that create microconduits upon
insertion and swelling in the skin, potentially allowing prolonged drug delivery without generating sharps waste.
Delivering hydrophobic drugs using HFMAPs poses challenges, which can be addressed using solubility enhancers such as cyclodextrins (CDs). This study aimed to deliver risperidone (RIS) transdermally using HFMAPs.
To enhance the aqueous solubility of RIS hydroxypropyl-beta-cyclodextrin (HP-β-CD) and hydroxypropylgamma-cyclodextrin (HP-γ-CD) were utilised and their performance was tested using phase solubility studies.
The aqueous solubility of RIS was enhanced by 4.75-fold and 2-fold using HP-β-CD and HP-γ-CD, respectively.
RIS-HP-β-CD complex (CX) and physical mixture (PM) directly compressed tablets were prepared and combined
with HFMAPs. Among the tested formulations, RIS-HP-β-CD PM reservoirs with 11 x 11 PVA/PVP HFMAPs
exhibited the best performance in ex vivo studies and were further evaluated in in vivo experiments using female
Sprague Dawley rats. The extended wear time of the MAPs resulted in the sustained release of RIS and its active
metabolite 9-hydroxyrisperidone (9-OH-RIS) in plasma samples, lasting from 3 to 5 days with a 1-day application
and up to 10 days with a 5-day application. For a 1-day application, HFMAPs showed greater systemic exposure
to RIS compared to intramuscular control (AUC0-t: 13330.05 ± 2759.95 ng/mL/hour versus 2706 ± 1472 ng/
mL/hour). Moreover, RIS exposure was extended to 5 days (AUC0-t: 12292.37 ± 1801.94 ng/mL/hour). In
conclusion, HFMAPs could serve as an alternative for delivering RIS in a sustained manner, potentially improving
the treatment of schizophrenia.