title: In vitro permeation of carvedilol through porcine skin: effect of vehicles and penetration enhancers.
abstract: This investigation studied the effect of vehicles on the in vitro permeation of carvedilol from saturated solutions across porcine skin and selected appropriate penetration enhancers. Labrasol, Transcutol, polyethylene glycol 400, propylene glycol, ethanol, oleic acid, isopropyl myristate, and phosphate buffered saline (pH 7.4) containing 40% v/v polyethylene glycol 400 as control, were used as vehicles; limonene, carvone, camphor, menthol, Transcutol, and Labrasol at 5% w/v concentrations were used as penetration enhancers. Skin permeation studies were conducted in Franz diffusion cells using excised porcine ear skin. Solubility was highest (369.13 mg/mL) in Transcutol, whereas isopropyl myristate showed the lowest solubility (0.79 mg/mL) among all the vehicles. The flux of carvedilol from Transcutol, Labrasol, polyethylene glycol 400, ethanol, and oleic acid was 10.5, 8.6, 4.2, 2.9, and 1.5 times higher, respectively, than that observed with control. The flux obtained using Transcutol was significantly higher (P < 0.05) than the flux obtained using the other vehicles. However, the flux values of carvedilol using isopropyl myristate (P < 0.01) and propylene glycol (P < 0.05) were significantly lower than that of the control. Solutions containing 5% w/v camphor showed maximum permeation (232.54 microg) in 24 h with a flux of 3.19 microg/cm2/h, which was significantly different (P < 0.05) than the flux obtained using other permeation enhancers. The control sample showed lowest permeation (30.50 microg), with a flux of 0.33 microg/cm2/h. The flux of carvedilol from the solutions containing 5% w/v camphor, limonene, Transcutol, carvone, Labrasol, and menthol were 9.7, 7.6, 7.6, 6.3, 4.7, and 2.3 times higher, respectively, than that observed using the control. The present study suggests that Transcutol, Labrasol, and polyethylene glycol 400 may be used as potential vehicles and camphor, limonene, and Transcutol at a 5% w/v level as penetration enhancers.
authors.affiliation: Centre for Biopharmaceutics and Pharmacokinetics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506 009 (A.P), India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Gannu
authors.forename: Y Vamshi
authors.initials: YV
authors.lastname: Vishnu
authors.forename: V
authors.initials: V
authors.lastname: Kishan
authors.forename: Y Madhusudan
authors.initials: YM
authors.lastname: Rao
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000737:chemistry; D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002164:Camphor / Q000737:chemistry; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000077261:Carvedilol; D053138:Cyclohexenes / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D000431:Ethanol / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry; D005989:Glycerides; D066298:In Vitro Techniques; D000077222:Limonene; D008610:Menthol / Q000737:chemistry; D009226:Myristates / Q000737:chemistry; D019301:Oleic Acid / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019946:Propylene Glycol / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013552:Swine; D013678:Technology, Pharmaceutical / Q000379:methods; D013729:Terpenes / Q000737:chemistry
chemical_list: D000277:Adjuvants, Pharmaceutic; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D053138:Cyclohexenes; D005026:Ethylene Glycols; D005989:Glycerides; D009226:Myristates; D009930:Organic Chemicals; D014677:Pharmaceutical Vehicles; D011412:Propanolamines; D013729:Terpenes; C440220:Labrasol; D000077261:Carvedilol; C008205:isopropyl myristate; D008610:Menthol; D019301:Oleic Acid; D000431:Ethanol; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D002164:Camphor; D000077222:Limonene; C010111:carbitol