title: Development and characterization of colloidal soft nano-carriers for transdermal delivery and bioavailability enhancement of an angiotensin II receptor blocker.
abstract: The purpose of this study was to develop and characterize a successful colloidal soft nano-carrier viz. microemulsion system, for the transdermal delivery of an angiotensin II receptor blocker: olmesartan medoxomil. Different microemulsion formulations were prepared. The microemulsions were characterized visually, with the polarizing microscope, and by photon correlation spectroscopy. In addition, the pH and conductivity (σ) of the formulations were measured. The type and structure of microemulsions formed were determined using conductivity measurements analysis, Freezing Differential Scanning Calorimetry (FDSC) and Diffusion-Ordered Spectroscopy (DOSY). Alterations in the molecular conformations of porcine skin were determined using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) biophysical assessment. Olmesartan medoxomil delivery from the investigated formulations was assessed across porcine skin ex-vivo using Franz diffusion cells; the drug was analyzed by liquid chromatography mass spectroscopy (LC/MS/MS). A comparative pharmacokinetic study was done on healthy human subjects between the selected microemulsion and the commercial oral tablets. The physico-chemical and spectroscopic methods revealed the presence of water-in-oil and bicontinuous structures. Biophysical assessment demonstrated various stratum corneum (SC) changes. Olmesartan medoxomil was delivered successfully across the skin with flux achieving 3.65μgcm(-2)h(-1). Higher bioavailability compared to commercial oral tablets with a more sustainment behavior was achieved.
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. r_hathout@yahoo.com
authors: Rania M
authors: RM
authors: Hathout
authors: Ahmed H
authors: AH
authors: Elshafeey
mesh_terms: D000279:Administration, Cutaneous; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003102:Colloids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D000068557:Olmesartan Medoxomil; D010316:Particle Size; D012867:Skin / Q000378:metabolism; D012995:Solubility; D013552:Swine; D013607:Tablets / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D057911:Angiotensin Receptor Antagonists; D003102:Colloids; D004337:Drug Carriers; D004655:Emulsions; D007093:Imidazoles; D013607:Tablets; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; C437965:olmesartan