title: Ethosomal Hydrogel of Raloxifene HCl: Statistical Optimization & Ex Vivo Permeability Evaluation Across Microporated Pig Ear Skin.
abstract: BACKGROUND
  The oral bioavailability of Raloxifene hydrochloride, an FDA approved selective estrogen receptor modulator, is severely limited due to its poor aqueous solubility and extensive first pass metabolism. The Present work focuses on the development of ethosomal hydrogel for transdermal delivery of Raloxifene HCl as an alternate way to solve aforementioned problem. The physical breaching of stratum corneum, the principal barrier, by microneedle treatment was also employed to potentiate its transdermal permeation.
  
  
  METHODS
  The influence of lipid and ethanol concentration on vesicle size and entrapment efficiency was extensively investigated using response surface methodology based on central composite design. The software based optimization was done and validated using check point analysis. Optimized batch was extensively evaluated for its safety, efficacy and stability.
  
  
  RESULTS
  The optimized ethosomal batch possessed 403 nm size and 74.25% drug entrapment. Its zeta potential and in vitro drug release were also found favorable for transdermal permeation. The ex vivo skin permeation study revealed a transdermal flux of 4.621 μg/cm2/h through the intact pig ear skin which was further enhanced through the microporated skin (transdermal flux, 6.194 μg/cm2/h) with a 3.87 fold rise when compared to drug permeation from plain solution applied over intact skin (transdermal flux, 1.6 μg/cm2/h). Histopathological skin sections showed the non-irritant nature of the ethosomal hydrogel and microneedle treatment. The formulation was found stable under both refrigeration and room temperature conditions for 6 weeks.
  
  
  CONCLUSIONS
  In a nutshell, the developed system was found efficient, safe and stable and seems promising for transdermal use.
authors.affiliation: Pharmacy Department, Faculty of Technology & Engineering, The M. S. University of Baroda, Kalabhawan, Vadodara-390001, Gujarat, India.
authors.forename: Hetal P
authors.initials: HP
authors.lastname: Thakkar
authors.forename: Hitesh
authors.initials: H
authors.lastname: Savsani
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D004423:Ear; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008845:Microinjections; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000737:chemistry; D012867:Skin / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
chemical_list: D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D010713:Phosphatidylcholines; D020845:Selective Estrogen Receptor Modulators; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020849:Raloxifene Hydrochloride