Fabrication and Characterization of Dissolving Microneedles for Transdermal Drug Delivery of Apomorphine Hydrochloride in Parkinson's Disease

Abstract

Purpose: We fabricated and characterized polyvinyl alcohol (PVA)-based dissolving microneedles (MNs) for transdermal drug delivery of apomorphine hydrochloride (APO), which is used in treating the wearing-off phenomenon observed in Parkinson's disease.

Methods: We fabricated MN arrays with 11 × 11 needles of four different lengths (300, 600, 900, and 1200 μm) by micromolding. The APO-loaded dissolving MNs were characterized in terms of their physicochemical and functional properties. We also compared the pharmacokinetic parameters after drug administration using MNs with those after subcutaneous injection by analyzing the blood concentration of APO in rats.

Results: PVA-based dissolving MNs longer than 600 μm could effectively puncture the stratum corneum of the rat skin with penetrability of approximately one-third of the needle length. Although APO is known to have chemical stability issues in aqueous solutions, the drug content in APO-loaded MNs was retained at 25°C for 12 weeks. The concentration of APO after the administration of APO-loaded 600-μm MNs that dissolved completely in skin within 60 min was 81%. The absorption of 200-μg APO delivered by MNs showed a T_max of 20 min, C_max of 76 ng/mL, and AUC_{0-120 min} of 2,829 ng・min/mL, compared with a T_max of 5 min, C_max of 126 ng/mL, and AUC_{0-120 min} of 3,224 ng・min/mL for subcutaneous injection. The bioavailability in terms of AUC_{0-120 min} of APO delivered by MNs was 88%.

Conclusion: APO-loaded dissolving MNs can deliver APO via skin into the systemic circulation with rapid absorption and high bioavailability.

Keywords: Apomorphine hydrochloride; Parkinson’s disease; dissolving microneedle array; polyvinyl alcohol; transdermal drug delivery system.