1. Directly Compressed Tablets: A Novel Drug-Containing Reservoir Combined with Hydrogel-Forming Microneedle Arrays for Transdermal Drug Delivery
- Author
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Li Zhao, Dk Siti Zawanah Binti Pg Hj Zahari, Ismaiel Tekko, Nava Shterman, Ryan F. Donnelly, Galit Levin, Aaron J. Courtenay, Aoife M. Rodgers, Helen O. McCarthy, Stephen Kelly, Anastasia Ripolin, Helen L. Quinn, Bridie Dutton, Etgar Levy-Nissenbaum, Lilach Steiner, Emma McAlister, and Lalitkumar K. Vora
- Subjects
Drug ,Vinyl alcohol ,Microinjections ,media_common.quotation_subject ,Biomedical Engineering ,Pharmaceutical Science ,02 engineering and technology ,010402 general chemistry ,Administration, Cutaneous ,01 natural sciences ,Biomaterials ,chemistry.chemical_compound ,Drug Delivery Systems ,Pharmacokinetics ,In vivo ,Animals ,Transdermal ,media_common ,Skin ,Aqueous solution ,Chromatography ,Aqueous medium ,Hydrogels ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Rats ,In vitro permeation ,chemistry ,Needles ,0210 nano-technology ,Tablets - Abstract
Microneedle (MN) patches consist of a hydrogel-forming MN array and a drug-containing reservoir. Drug-containing reservoirs documented in the literature include polymeric films and lyophilized wafers. While effective, both reservoir formulations are aqueous based, and so degradation can occur during formulation and drying for drugs inherently unstable in aqueous media. The preparation and characterization of novel, nonaqueous-based, directly compressed tablets (DCTs) for use in combination with hydrogel-forming MN arrays are described for the first time. In this work, a range of drug molecules are investigated. Precipitation of amoxicillin (AMX) and primaquine (PQ) in conventional hydrogel-forming MN arrays leads to use of poly(vinyl alcohol)-based MN arrays. Following in vitro permeation studies, in vivo pharmacokinetic studies are conducted in rats with MN patches containing AMX, levodopa/carbidopa (LD/CD), and levofloxacin (LVX). Therapeutically relevant concentrations of AMX (≥2 µg mL-1 ), LD (≥0.5 µg mL-1 ), and LVX (≥0.2 µg mL-1 ) are successfully achieved at 1, 2, and 1 h, respectively. Thus, the use of DCTs offers promise to expand the range of drug molecules that can be delivered transdermally using MN patches.
- Published
- 2020