The effect of terpenes on percutaneous absorption of tiaprofenic acid gel.
Tiaprofenic acid is a potent analgesic and nonsteroidal anti-inflammatory drug (NSAID) and like any other nonsteroidal anti-inflammatory drug, oral administration of the conventional dosage forms of tiaprofenic acid invariably causes gastrointestinal side effects. In an effort to eliminate these side effects while enhancing the drug concentration at the target tissue, an epidermal application of tiaprofenic acid seems to be an effective alternative drug delivery modality. This study attempts to demonstrate the influence of different terpenes (d-limonene, menthol and nerolidol) in various combinations of preparations on the percutaneous penetration of tiaprofenic acid from Carbopol(®) 940 based gel formulations (1%) in an ex vivo experiment using Franz-type diffusion cells. The enhancement effect of terpenes on skin absorption of tiaprofenic acid was further evaluated by an in vivo method in rats. Amongst the terpenes used, d-limonene was the most outstanding penetration enhancer that was reference to penetration of tiaprofenic acid through rat skin ex vivo. In vivo penetration study shows that the AUC₀(-)₄₈(h) was increased by about 10 fold by the addition of 5% d-limonene to the formulation. Histological studies show that d-limonene causes disruption on the skin surface and is responsible for enhanced penetration of tiaprofenic acid. Since tiaprofenic acid is known to cause gastrointestinal disturbances following systemic administration, topical formulations of tiaprofenic acid in gel form including 5% d-limonene could be suggested as an alternative.
Department of Pharmacology, Istanbul University, Beyazit-Istanbul, Turkey. aokyar@istanbul.edu.tr
Alper
A
Okyar
Maksat
M
Nuriyev
Ayca
A
Yildiz
Zeliha
Z
Pala-Kara
Narin
N
Ozturk
Engin
E
Kaptan
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D053138:Cyclohexenes / Q000494:pharmacology; D004304:Dosage Forms; D016503:Drug Delivery Systems; D005782:Gels / Q000378:metabolism / Q000494:pharmacology; D000077222:Limonene; D008297:Male; D008610:Menthol / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011422:Propionates / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053138:Cyclohexenes; D004304:Dosage Forms; D005782:Gels; D011422:Propionates; D012717:Sesquiterpenes; D013729:Terpenes; D008610:Menthol; C021270:tiaprofenic acid; D000077222:Limonene; C037055:nerolidol