Title : Absorption enhancing capacity of dissolving microneedle arrayed patches
Abstract:
The microneedle-mediated transdermal delivery system has been developed to provide minimal invasive selfadministration method with patient friendly manner. Especially, dissolving microneedles, which deliver the target drugs as the drug-loaded microneedle or medical device to enhance absorption dissolves into the skin, have been developed recently. Conventional dissolving microneedle fabrication methods, stepwise casting method in 3D molds, have problems to standardize the drug dose and to maintain the activity of labile drug during the manufacturing process. Droplet-born air blowing (DAB) method has great advantages in stability with precise dose control because DAB provide quick manufacturing process with ambient temperature. The purpose of this study is to show the characteristics of dissolving microneedles as medical device, which manufactured in our mass production system. Microneedle fabricated by DAB (Droplet-born Air Blowing) method. Briefly, Biodegradable polymer such as HA (hyaluronic acid) was dissolved in distilled water with active ingredient (in case of drug-loaded microneedle). The polymer was dropped to patch, and each droplet is shaped to the microneedle. The loaded amount of AA2G (Ascorbic Acid 2-Glucoside) was analyzed by HPLC/UV system (Waters, e2695). And, Skin permeability of microneedle was confirmed by OCT (optical coherence tomography) and delivered amount of drug into the skin was analyzed using Franz diffusion cell (Logan, FDC-6T). We optimized the DAB process parameters and scaled up. 350 µm length of microneedles were fabricated and dried within 10 min without applying any heat or uv light which could cause any degradation of active ingredient. The active ingredient was stable within microneedle during 2 months at 25 °C and 45 °C. In vitro studies of skin permeability as drug-loaded microneedle using Franz diffusion cell showed excellent delivery efficiency compared to topical solution. Most of the loaded anti-oxidants was delivered through the skin after 24hr (98.0±2.0%, n=3). The microneedles dissolution in skin was confirmed, so the drugs within microneedle should be delivered into the intradermal region. For analyzing characteristics of absorption enhancement as medical device, Betamethasone valerate ointment (0.57 mg/ml in ethanol) was applied on the 3D skin model (Strat-MTM, EMD Millipore Corporation, Germany). Dissolving microneedle patch was applied onto the 3D skin model after betamethasone valerate solution application to measure the delivery efficacy of betamethasone valerate using franz diffusion cell. In vitro studies using Franz diffusion cell showed excellent delivery efficiency about 2.5 times compared to applying only ointment (Betamethasone Valerate).
Takeaway Notes:
•Optimized DAB (Droplet-born Air Blowing) process
•High skin permeability of API (cosmetic ingredients) as drug-loaded microneedle
•To enhance API (ointment) absorption into skin by microneedle arrayed patch
•Suitable skin permeability assay design for microneedle arrayed patch application
