]. Cosmet. Sci., 59, 385-398 (September/October 2008) Evaluation of liposomal and conventional formulations of octyl methoxycinnamate on human percutaneous absorption using the stripping method S. GOLMOHAMMADZADEH, M. R.JAAFARI, and N. KHALILI, Department of Pharmaceutics, School of Pharmacy (S. G., M. R.j., N. K.), and Pharmaceutical Research Center (S. G., N. K.) and Biotechnology Research Center ( M. R. J. ), Mashhad University of Medical Sciences, Mashhad, Iran. Accepted for Publication February 29, 2008. Synopsis The objective of this study was to determine the influence of vehicles on the penetration of octyl methoxy­ cinnamate (OMC), as a UV absorber, to the stratum corneum by the stripping method. The experimental formulations consisted of a conventional o/w emulsion and multilamellar and small unilamellar liposomes (MLVs and SUVs) containing OMC. MLVs containing OMC were prepared by the fusion method and then converted to SUVs by probe sonication. Various formulations were then applied onto the midvolar forearms of six volunteers at a dose of 2 mg/cm 2. After determined timepoints, the stripping method was conducted whereby 22 tape strips were applied and subsequently divided into different stripping groups. The sunscreen agent was assessed by HPLC while the SPF (sun protection factor) of the formulations was determined in human volunteers in accordance with the Australian standard. Overall the results indicate that skin accu­ mulation of OMC in MLVs was significantly greater than in the o/w emulsion and SUVs. Furthermore, SUV's penetration into the deeper skin layers was significantly greater than Ml V's and that of a conven­ tional o/w emulsion. Also, higher amounts of OMC were recovered from the upper layers of the stratum corneum than from the deeper layers in all the formulations tested. Finally, the SPF of the liposomes containing OMC was slightly greater than that of the control lotions at a similar concentration of OMC. In conclusion, the result of this study indicates that an ML V prepared by the fusion method could be a better vehicle for OMC as a sunscreen since it has a slightly better SPF compared to a conventional formulation and more remains in the stratum corneum, reducing its penetration to the deeper layers. INTRODUCTION Despite a proven beneficial effect from sun-emitted radiation, the sun also emits ultra­ violet radiation, which is hazardous to the health of human skin (1,2). Various studies demonstrate the damaging influence of solar radiation on skin (3,4), identifying UV-A and UV-B as the main culprits. These components are primarily responsible for skin Address all correspondence to M. R. Jaafari. 385

386 JOURNAL OF COSMETIC SCIENCE pathologies such as sunburns, photosensitivity, phototoxicity, actinic elastosis, photo­ aging, immunosuppression, and skin cancer (2,5). In order to combat these detrimental effects of solar radiation, sunscreen has been utilized for decades as a means of protection (6,7). However sunscreen's effectiveness is not optimal due to the numerous factors affecting the delivery of the drugs and cosmetics into the skin from topically applied formulations. These factors include the physico­ chemical properties of the drug, the size of the molecule, the lipophilicity of the components in the vehicle, the type of the formulation and vehicle, the presence of penetration enhancers, and the physical state of the stratum corneum (8-10). For a sunscreen to be effective, the UV absorbers must remain in the outermost region of the skin. An ideal sunscreen product should exhibit high skin accumulation of UV absorbers with minimal permeation to the circulation (5,11). Therefore, to be efficient and to avoid toxicity, sunscreens should stay on the skin surface and penetrate minimally through the skin. However, it has been demonstrated that penetration into the skin, permeation through the skin, and retention of UV filters in the skin from topical products can differ significantly among formulations (11,12). Treffel and Gabard (7) showed that sunscreen agents were better retained in the stratum corneum in an emul­ sion-type formulation rather than in petrolatum jelly. In addition, recent studies have demonstrated that sunscreens are absorbed systemically following topical application to the skin (12-14). Since sunscreen products are generally applied to the skin superficially, their effective­ ness is determined by how the product adheres to the skin as a protective film. Fur­ thermore, sunscreens should also have a high affinity for the stratum corneum (12,15). Thus the sunscreen's vehicle can affect the solubility properties of a solute and therefore influence the percutaneous absorption that may enhance or inhibit the movement of the UV filter through the skin (13,16). Since the degree of penetration depends strongly on the physicochemical properties of the active compounds and the nature of the vehicle (9,17), the development of suitable products that prevent penetration of the sunscreen into the skin is a challenge for manufacturers of cosmetic products (17). Liposomes, small vesicles composed of phospholipids, have been used for years to bring active ingredients into the skin (10,18-20). Several factors, such as the physicochemical properties of the drug and other ingredients present in the liposomal product, lamel­ larity, lipid composition, charge on the liposomal surface, the size of the liposomes, the vehicle, the mode of application, and the total lipid concentration have been proven to influence drug deposition into the skin layers (8, 10,21). It has been demonstrated that liposomes can cross the stratum corneum and act as microreservoirs from which drugs may be slowly released (9, 19,22). Liposomes can provide a drug-delivery system that delivers several-fold higher drug concentrations into the skin with lower systemic ab­ sorption compared to conventional dosage forms (10,18,19,23). Another advantage of a liposome-based controlled-released system is that less drug needs to be administered for comparable efficacy. Thus, the probability of systemic absorption and consequent ad­ verse drug reactions is reduced (9,20). There are also studies that have shown that liposomes can enhance the penetration of drugs into the skin or enhance the transdermal flux of drugs, but at the same time some reports also claim a lack of this effect (8,10,24,25). Even though most of the time reducing the size of liposomes enhances the skin penetration, in some cases liposomes with small sizes have shown less penetration into the skin, depending on the drugs incorporated (26).