title: Preparation and evaluation of 5, 9-dimethyl-2-cyclopropyl-2-decanol as a penetration enhancer for drugs through rat skin.
abstract: In the present study a new alcohol derivative of tetrahydrogeraniol (THG), an acyclic monoterpene, has been prepared by using Grignard reagent and methyl cyclopropyl ketone. Penetration enhancing effects of THG and the synthesized derivative 5,9-dimethyl-2-cyclopropyl-2-decanol (DICNOL) on the transdermal penetration of 5-fluorouracil (5-FU) and tramadol hydrochloride (tramadol HCl) across the excised rat skin were studied by an in vitro permeation technique using Franz diffusion cells. Azone was used as standard enhancer for comparison. DICNOL and THG significantly enhanced 5-FU and tramadol HCl penetration through rat skin compared with the control. DICNOL enhanced the permeability of 5-FU and tramadol HCl across full thickness skin by about 11 and 20 fold, respectively. Increased partition coefficient and diffusion coefficient values were obtained by these enhancers. The results suggest that the amount of DICNOL in the skin, especially in the stratum corneum, may be related to its penetration enhancing effects.
authors.affiliation: Drug Delivery Research Centre, Department of Pharmaceutics, Gomal University, Dera Ismail Khan, Pakistan. drgulmajeed@yahoo.com
authors.forename: Gul Majid
authors.initials: GM
authors.lastname: Khan
authors.forename: Abid
authors.initials: A
authors.lastname: Hussain
authors.forename: Raja Muhammad
authors.initials: RM
authors.lastname: Hanif
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000138:chemical synthesis* / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D004058:Diffusion / Q000187:drug effects; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D010539:Permeability / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology; D014147:Tramadol / Q000378:metabolism
chemical_list: C570308:5,9-dimethyl-2-cyclopropyl-2-decanol; D000277:Adjuvants, Pharmaceutic; D001381:Azepines; D003521:Cyclopropanes; D005233:Fatty Alcohols; D004364:Pharmaceutical Preparations; D013729:Terpenes; C035229:laurocapram; D014147:Tramadol; C063573:3,7-dimethyloctan-1-ol; D005472:Fluorouracil