title: Development and evaluation of carvedilol-loaded transdermal drug delivery system: In-vitro and in-vivo characterization study.
abstract: BACKGROUND
  The transdermal drug delivery system was prepared and the bioavailability of the selected drug was enhanced by reducing first-pass metabolism.
  
  
  OBJECTIVE
  The objective of this study was to enhance the bioavailability of carvedilol through transdermal patches.
  
  
  METHODS
  To develop a matrix-type transdermal patch containing carvedilol with different ratios of polymer combinations by solvent evaporation technique.
  
  
  CONCLUSIONS
  In-vitro permeation studies were performed by Franz diffusion cells. The results followed Higuchi kinetics, and mechanism of release was diffusion mediated. On the basis of the in-vitro and physicochemical parameters of carvedilol patches, the code F-1(PVP: Ethyl Cellulose = 4:1) was chosen for the study of in-vivo, ex-vivo, histocompatibility study, and pharmacological study. The bioavailability studies in rats indicated that the carvedilol-loaded transdermal patches provided steady-state plasma concentration and improved bioavailability of 72% in comparison to oral administration. The ex-vivo permeation study in rat's skin indicated that the flux and permeability co-efficient of optimized F-1 patch was 30.08 ± 0.7 μg/cm(2)/h and 0.416 ± 0.05 μg/cm(2)/h, respectively, which was more as compared to plain carvedilol. The histocompatibility study of the F-1 patch on the rat's skin after 24 h ex-vivo study gave less pathological changes as compared to other. The antihypertensive activity of the patch in comparison with oral administration was studied using N-nitro-L-arginine methyl ester-induced hypertensive rats. It was observed that the optimized patch (F-1) significantly controlled hypertension (p < 0.05).
  
  
  CONCLUSIONS
  The developed patch increases the efficacy of carvedilol through enhancement of bioavailability for the therapy of hypertension.
authors.affiliation: Department of Quality Assurance Techniques and Department of Pharmaceutics, AISSMS College of Pharmacy, Pune, Maharashtra, India. sanjayjkshirsagar@gmail.com
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Kshirsagar
authors.forename: Mangesh R
authors.initials: MR
authors.lastname: Bhalekar
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Mohapatra
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077261:Carvedilol; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects; D057968:Transdermal Patch
chemical_list: D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol