J. Cosmet. Sci., 63, 397–406 (November/December 2012) 397 Characterization and release kinetics of nicotinamide microemulsion-based gels PRAPAPORN BOONME, NATTIYA SUKSAWAD, and SARUNYOO SONGKRO, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90112, Thailand. Accepted for publication April 13, 2012. Synopsis The aim of this study was to investigate physicochemical characteristics and to determine in vitro release ki- netics of prepared nicotinamide microemulsion-based gels (MBGs). Nicotinamide microemulsions (ME) were composed of 3% w/w nicotinamide, 7% w/w water, 25% w/w soybean oil, and 65% w/w of 9:1 oleth- 10:isopropyl alcohol mixture. A water-in-oil (w/o) type ME was converted to three MBGs. ME was combined with 5% w/w of colloidal silica to obtain MBG-1, with 5% w/w of 0.5% w/w carbomer solution to obtain MBG-2, or with a mixture of 3% w/w of 0.5% w/w carbomer solution and 2% w/w of PEG-40 hydrogenated castor oil to obtain MBG-3. The results indicated that MBG-1 was a clear gel with plastic fl ow while MBG-2 and MBG-3 were turbid gels with Newtonian fl ow. MBG-1 was physically and chemically stable at 4ºC as well as at ambient temperature (approximately 30ºC) during the 2-month study period. The color darkened when stored at 60ºC. The release kinetics of MBG-1 was best fi tted to zero order model. The in vitro release of nicotinamide from MBG-1 through cellulose membrane was compared with that from the ME and an oil- in-water (o/w) commercial cream (CC). The rank order of release rate of nicotinamide from different formula- tions was MBG-1 ME CC. INTRODUCTION Nowadays, white skin is preferable for Asian people since they think that whiteness means beauty and attractiveness. This belief is infl uenced by skin color of famous Asian singers and actors. For this reason, skin whitening products gain widespread acceptance and provide high income in cosmetic markets of Asia. Among many skin whitening agents, nicotinamide, commonly known as vitamin B3, is a widely used and well-known compound that can inhibit melanosome transfer from melanocytes to keratinocytes (1). It provides a safe mechanism since the inhibition process occurs after melanogenesis within the melanosome and does not affect intrinsic biosynthesis of melanin production, consid- ered to be safe and effective for use in skincare products for anti-aging, anti-infl ammatory, and depigmentation effects. Benefi ts of topical nicotinamide on the skin have been reported Address all correspondence to Prapaporn Boonme at prapaporn.b@psu.ac.th.

JOURNAL OF COSMETIC SCIENCE 398 (2–4). However, its hydrophilicity provides diffi cult penetration into the basal layer of the epidermis, its target site, due to the barrier function of the stratum corneum (5). Hence, novel formulations are necessary. Microemulsions (MEs) are novel carriers used in cosmetics and cosmeceuticals. They are thermodynamically stable, transparent, low-viscosity dispersions of oil and water stabilized by an interfacial fi lm of a surfactant and usually in combination with a cosurfactant such as a short-chain alcohol and a polyhydroxy compound. Many advantages can be obtained from topical MEs including enhanced aesthetics, thermodynamic stability, high solubilization power, ease of preparation, and skin penetration enhancement (6–9). Several researches have shown that MEs are effective vehicles for skin whitening agents such as ascorbyl palmitate (10), sodium ascorbyl phosphate (11), arbutin (12), kojic acid (12), and ascorbic acid (13). Application of MEs in skin whitening products was recently reviewed (14). In our previous study (15), phase behavior of systems composed of oleth-10, water, vari- ous oils, and various cosurfactants was investigated. The oils studied were silicone oil and soybean oil. The studied cosurfactants were isopropyl alcohol (IPA), propylene glycol, and sorbitan monooleate (Span 80). Various ratios of surfactant and cosurfactant were also studied. It was found that among investigated systems, the system of soybean oil, water, and 9:1 mixture of oleth-10 and IPA provided the largest ME region. In a subsequent study (16), two ME formulations designated as ME-1 and ME-2 were selected from this system to be incorporated with nicotinamide and then characterized for physicochemical properties and in vitro release profi les. The concentrations of nicotinamide, water, soybean oil, and surfactant mixture in ME-1 were 3% w/w, 7% w/w, 18% w/w, and 72% w/w, respectively. Those in ME-2 were 3% w/w, 7% w/w, 25% w/w, and 65% w/w, respec- tively. Both ME-1 and ME-2 were of water-in-oil (w/o) type. They had similar physico- chemical characteristics (i.e., conductivity, viscosity, class of fl ow, and particle size), stability, and in vitro release profi les. MEs can be used directly as drops or sprays however, they might not be suitable in some cases because of low adhesion. Conversion to gel form can overcome this problem. This study aimed to characterize physicochemical properties and to investigate in vitro release kinetics of the prepared nicotinamide ME-based gels (MBGs). EXPERIMENTAL METHODS MATERIALS Nicotinamide was obtained from Fluka (Buchs, Switzerland). Soybean oil was obtained from Thai Vegetable Oil Public Company (Bangkok, Thailand). Oleth-10 (Sympatents- AO/100®) was obtained from Kolb Distribution Ltd. (Hedingen, Switzerland). IPA was obtained from VRW International (Arlington Heights, IL). Colloidal silica was obtained from Sigma-Aldrich (St. Louis, MO ). Carbomer (Carbopol® Ultrez 21) was obtained from Lubrizol (Wickliffe, OH). Triethanolamine (TEA) was obtained from P.C. Drug Center (Bangkok, Thailand). PEG-40 hydrogenated castor oil was obtained from BASF (Morris County, NJ). Isotonic phosphate buffer pH 7.4 (IPB) was prepared in-house and composed of disodium hydrogen phosphate (Carlo-Erba, Milan, Italy), sodium dihydrogen orthophosphate (BDH Chemicals Ltd., East Yorkshire, UK), and sodium chloride (Carlo-Erba, Milan, Italy).