Abstract

Abstract

Topical delivery of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an inhibitor of collagen synthesis and a therapeutic drug for keloid and hypertrophic scar, was examined, in rats, with oleic acid alone or a combination of oleic acid and propylene glycol as penetration enhancer. Evaluation was by measurement of the concentration of tranilast in plasma and in the dialysate from skin microdialysis. When tranilast at a dose of 1.5 mg was applied topically as an ethanol solution containing 5% polyvinylpyrrolidone on a dorsal skin surface (2.25 cm2), the maximum concentration of tranilast in skin dialysate was approximately 2 microM. When 10 or 20% oleic acid was added to the same ethanol solution the maximum concentration of tranilast in the dialysate increased to 10-20 microM, and this value was further increased to 60 microM by the addition of a combination of oleic acid (10 or 20%) and propylene glycol (10%) to the solution. With the combination of oleic acid and propylene glycol the area under the plot of the concentration of tranilast in skin dialysate against time between 0 and 4 h (AUC0-4) was more than 400-fold that after intravenous administration. The transdermal bioavailability of tranilast as assessed by the AUC0-4 of tranilast in plasma, was 0.2% of the dose applied in the ethanol solution, 3-5% of that applied in the ethanol solution containing oleic acid, and 14-16% of that applied in the ethanol solution containing both oleic acid and propylene glycol. These results suggest that the topical delivery of tranilast with an absorption enhancer such as a mixture of oleic acid and propylene glycol might be a more effective medication than oral administration of tranilast for the treatment of keloid and hypertrophic scar.

Pretreatment with Skin Permeability Enhancers: Importance of Duration and Composition on the Delivery of Diclofenac Sodium

“…When the probe is perfused with an isotonic solution, a concentration gradient is created that allows for diffusion of drug from the dermal extracellular fluid into the perfusing fluid across the semipermeable membrane. Cutaneous microdialysis for the assessment of enhancer activity following topical application of drugs has been previously reported . This technique has also been successfully employed to study pharmacokinetics of drugs in rat dermis following topical application …”

Development and Evaluation of α-Asarone Transdermal Patches Based on Hot-Melt Pressure-Sensitive Adhesives

“…Limitations with the use of a single penetration enhancer can be effectively overcome by the synergistic effect of combining multiple penetration enhancers. Several studies described the combination of two or more penetration enhancers for transdermal delivery (22)(23)(24). In this study, transdermal flux was significantly increased by combining 4% MEN and 1% OA, showing a twofold higher flux rate than the control group and demonstrating a synergistic effect on promoting α-asarone percutaneous absorption.…”

Preclinical pilot study monitoring topical drug penetration and dermal bioavailability of a peptidase inhibitor from different galenic formulations into pig dermis, using cutaneous microdialysis

“…However, even a pH of 7.5 may be sufficiently suitable for acne treatment as it has been tested with different formulations containing erythromycin . Using CM, it has been shown in rats that the addition of 10% OA as a penetration enhancer greatly increased the amount of the permeated drug in the dermal dialysates …”

“…increased the amount of the permeated drug in the dermal dialysates. 24 This study was set up only as a pilot study to test whether it is possible to use this set-up for larger scales in preclinical testing to optimize the topical drug formulation before the clinical phase. One advantage of this technique is that it can be easily transferred to the clinical phase.…”