Glibenclamide Nanocrystals in a Biodegradable Chitosan Patch for Transdermal Delivery: Engineering, Formulation, and Evaluation

Glibenclamide (GBD) nanocrystals (D-50 = 429 nm) were engineered by applying combined precipitation and homogenization procedures. GBD crystallinity was maintained during the nanonization process as revealed by differential scanning calorimetry and X-ray analyses. Nanonized and micronized GBD were incorporated into chitosan solutions to fabricate transdermal delivery systems (TDDSs), nano- and micro-GBD, respectively. The fabricated TDDSs displayed satisfactory physicochemical characteristics without substantial aggregation of GBD nanocrystals during the casting and drying procedures. Within 24 hours, about 85 +/- 3.1% of the GBD content was released from nano-GBD, compared to 61 +/- 3.9% from micro-GBD. Cumulative permeation of GBD from nano-GBD after 24 hours was 498 +/- 33.35 compared to 362 +/- 25.25 mu g/cm(2) from micro-GBD. The calculated flux across rat skin for nano-GBD was 23.14 compared to 13.64 mu g/cm(2)/h for micro-GBD, with an enhancement factor of 1.7. In vivo assessment clearly revealed the enhanced efficacy of nano-GBD to reduce blood glucose levels and counteract the induced hyperglycemia in tested animals compared to micro-GBD (p < 0.5). Simultaneously, the nano-GBD was able to maintain higher drug concentration for longer time (24 hours, p < 0.5) and minimize intense action and hypoglycemia associated with GBD oral therapy (p < 0.5). (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.