Effect of Penetration Enhancers on Transdermal Delivery of Propofol

Abstract

Transdermal therapeutic systems, intended to deliver a drug across skin for systemic activity, are receiving attention because these systems can (1) avoid hepatic first-pass metabolism, (2) maintain blood drug levels for an extended period of time by controlling the drug-release rate and (3) allow easy interruption of drug delivery.1,2) However, the stratum corneum is known to be a major barrier to drug permeation through the keratinized epithelium. Due to the poor skin permeation of drugs, transdermal administration is often limited.3) For enhancing drug delivery across the skin, the efficacy of penetration enhancers has been investigated.4) The penetration enhancers are generally classified as membraneacting types or co-solvent types. The membrane-acting types, such as fatty acid, 5-7) terpene [8][9][10] and surfactant, [11][12][13] achieve effects using small amounts by altering the condition of the lipid membrane constituting the stratum corneum. The co-solvent types, such as propylene glycol (PG), 10,14) polyethylene glycol 15) and ethanol, 8) achieve effects by improving the solubility of drugs or enhancing permeation of drugs through the skin.Propofol (PF), a lipophilic anesthetic, is widely used clinically as it (1) has a rapid onset and cessation of effects upon intravenous infusion, (2) accumulates little and induces a brief but profound anesthesia, (3) maintains a level in circulation similar to the levels achieved by inhalation anesthetics. The characteristics of PF, lipophilicity and low molecular weight (MWϭ178), is suited to the transdermal delivery. 16)Furthermore, as PF exists in the liquid state above 20°C, a high-concentration PF solution can be prepared. In the previous study, we confirmed that PF was absorbed through rat skin and induced a sedative effect in rats.17) By transdermal delivery of PF, the blood level of the drug can be maintained for an extended period of time. Hence, a possibility that PF can be developed as a transdermal dosage form of sedative or hypnotic is considered. In this study, the in vitro skin permeability and the in vivo absorbability of PF were investigated in rats using PF solutions containing various types of enhancers. Then, we estimated the effectiveness of enhancers on the transdermal delivery of PF. (Osaka, Japan) as the purest grade available. Macrogol 400 (MG) was of Japanese Pharmacopoeia (JP) grade. Sucrose fatty acid esters were obtained from MitsubishiKagaku Foods Corporation (Tokyo, Japan). We used four kinds of sucrose fatty acid esters (L595, L1695, O1570 and S1570). L, O and S indicate lauric acid, oleic acid and stearic acid, respectively. The hydrophilic lipophilic balance (HLB) values of L595, L1695, O1570 and S1570 were 5, 16, 15 and 15, respectively. All other chemicals were obtained commercially as the purest grade available. MATERIALS AND METHODS MaterialsAnimals Male Sprague-Dawley rats weighing approximately 200-220 g were purchased from Tokyo Laboratory Animals Science Co., Ltd. (Tokyo, Japan). The experimental protocol was approved by the...

Effect of Aqueous Cream BP on human stratum corneum in vivo

“…SLS is an anionic, amphiphilic surfactant extensively used for its solubilizing, wetting, suspension, stabilization and emulsifying properties in consumer and industrial products ranging from food to pharmaceutical preparations 18 . In skin research, SLS is a known enhancer of drug permeation across the skin, 4,12 has induced damage to the barrier to mimic the effects of skin disease, and has been used to elicit skin irritation in experimental models of irritant contact dermatitis 4–11,19,20 …”

“…While the origin of the reaction may be due to the presence of either a preservative or an antiseptic in the formulation (respectively, chlorocresol and phenoxyethanol), which have been reported as skin irritants, 2,3 an equally likely suspect is sodium lauryl sulphate (SLS), an anionic surfactant and emulsifier that is a well‐known irritant. Numerous reports in the literature attest to the ability of SLS to increase the permeability of the skin barrier and it is often used as a model irritant in experimental studies 4–12 . It should also be highlighted that Aqueous Cream BP was initially designated as a wash product rather than as a leave‐on emollient, i.e.…”

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.…”

Transdermal Iontophoretic Delivery of Propofol: A General Anaesthetic in the Form of its Phosphate Salt

“…PG is known to increase the solubility of drugs in the skin lipids and thereby enhance the permeability of therapeutic agents. Yamato et al22 studied the effect of different CPEs on transdermal permeation of propofol. The authors reported a fourfold enhancement in the in vitro permeation flux of propofol across the rat abdominal skin when 30% PG was used as CPE 22.…”