title: Glibenclamide Nanocrystals in a Biodegradable Chitosan Patch for Transdermal Delivery: Engineering, Formulation, and Evaluation.
abstract: Glibenclamide (GBD) nanocrystals (D50= 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 μg/cm2from micro-GBD. The calculated flux across rat skin for nano-GBD was 23.14 compared to 13.64 μg/cm2/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).
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt. Electronic address: hsali@taibahu.edu.sa.
authors.forename: Hany S M
authors.initials: HSM
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; Research and Development Department, European Egyptian Pharmaceutical Industries, Alexandria, Egypt. Electronic address: akorayem@yahoo.com.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Hanafy
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D003460:Crystallization; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D005905:Glyburide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D057968:Transdermal Patch; D014961:X-Ray Diffraction
chemical_list: D007004:Hypoglycemic Agents; D048271:Chitosan; D005905:Glyburide
keywords: chitosan; nanoparticles; permeability; pharmacodynamics; transdermal delivery systems