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

Area of Science:

• Pharmaceutical Sciences
• Biomaterials Science
• Drug Delivery Systems

Background:

• Hydrophobic drugs present challenges for transdermal delivery.
• Hydrogel-forming microneedle array patches (HFMAPs) offer prolonged drug delivery without sharps waste.
• Cyclodextrins (CDs) can enhance the solubility of hydrophobic drugs.

Purpose of the Study:

• To develop and evaluate HFMAPs for transdermal risperidone (RIS) delivery.
• To enhance RIS aqueous solubility using hydroxypropyl-beta-cyclodextrin (HP-β-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD).
• To assess the in vivo sustained release and systemic exposure of RIS delivered via HFMAPs.

Main Methods:

• Phase solubility studies were conducted to evaluate RIS solubility enhancement with HP-β-CD and HP-γ-CD.
• RIS-HP-β-CD complex and physical mixture formulations were prepared for HFMAPs.
• Ex vivo and in vivo studies in Sprague Dawley rats were performed to evaluate HFMAP performance.

Main Results:

• HP-β-CD enhanced RIS aqueous solubility by 4.75-fold, and HP-γ-CD by 2-fold.
• RIS-HP-β-CD physical mixture HFMAPs showed optimal performance in ex vivo studies.
• In vivo studies demonstrated sustained RIS and 9-hydroxyrisperidone (9-OH-RIS) plasma levels for 3-10 days post-application.
• HFMAPs provided significantly greater systemic exposure to RIS compared to intramuscular injection for a 1-day application.

Conclusions:

• HFMAPs are effective for sustained transdermal delivery of risperidone.
• The use of HP-β-CD significantly enhances RIS solubility for HFMAP formulation.
• HFMAPs represent a promising alternative for improved schizophrenia treatment through prolonged risperidone delivery.