Dissolving Microneedles Loaded With Etonogestrel Microcrystal Particles for Intradermal Sustained Delivery

The study design is that lipophilic drug was encapsulated within dissolving microneedles (DMNs) for sustained-release delivery over 1 week. Etonogestrel (ENG), the progestogen used in hormonal contraceptives, was loaded in 2-layered DMNs in the form of microcrystal particles (MPs). In vitro release study indicated that ENG in the MP form could sustain drug release compared to noncrystal form. Hydroxypropyl methylcellulose and polyvinyl alcohol were used to prepare the fast dissolving needle tips and flexible back layer, respectively. The mechanical strength of microneedles was not affected even with the drug-loading efficiency of 50.0% in needle tips. The penetration depth of DMNs in skin, observed using a confocal laser scanning microscope, was approximately 280 mm. The tips of DMNs could be dissolved in rat skin within 1 h with a drug delivery efficiency of 63.8 +/- 2.0%. The pharmacokinetic study of DMN treatment in rats showed that the plasma levels of ENG were a dose-dependent profile and were much steadier than intradermal (ID) injections. There was no statistical difference between bioavailability of ENG treated with DMNs or ID injections (p > 0.05). Therefore, the novel DMNs loaded with drug MP provided a potential minimally invasive route for ID sustained delivery of lipophilic drug. (C) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.