การปลดปล อยไนอาซ นาไมด และคาเฟอ นจากคร มชน ดต างๆ บทค ดย อ

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1 การปลดปล อยไนอาซ นาไมด และคาเฟอ นจากคร มชน ดต างๆ จร ยาพร พ มสก ล*, ส น ย ชาญณรงค การปลดปล อยไนอาซ นาไมด และคาเฟอ นจากคร มชน ดต างๆ จร ยาพร พ มสก ล 1 1 *, ส น ย ชาญณรงค บทค ดย อ 007HCU งานว จ ยน เป นการเตร ยมตาร บและศ กษาการปลดปล อยไนอาซ นาไมด (ว ตาม นบ 3) และคาเฟอ นจากคร มเบสสามชน ดท แตกต างก น ค อ vanishing cream, hydrophilic emulsion และ cold cream การปลดปล อยของสารสาค ญศ กษาโดยใช Franztype diffusion cells และเมม เบรนส งเคราะห เป นเย อก น ท ง vanishing cream และ hydrophilic emulsion เป นคร มชน ดน าม นในน า ท แตกต างก นตรงชน ดของของสารก อ อ ม ลช นและชน ดของน าม นท ใช ทาให คร ม vanishing cream ม ล กษณะท เหลวกว า hydrophilic emulsion ส วน cold cream เป นคร มชน ดน าใน น าม น และคร มท ได ม ความหน ดมากท ส ด ในการศ กษาการปลดปล อยในหลอดทดลองของไนอาซ นาไมด และคาเฟอ นจากคร มพ นชน ด o/w ม จลนศาสตร การปลดปล อยเป นไปตาม Higuchi ส วนชน ด w/o ม จลนศาสตร การปลดปล อยเป นไปตามสมการอ นด บหน ง สารท งสองชน ด สามารถปลดปล อยได ค า flux มากและอ ตราเร วส งท ส ดจากคร มพ นชน ด vanishing cream และปลดปล อยได ค าน อยท ส ดจากคร มพ นชน ด cold cream จากผลการศ กษาการปลดปล อยน พบว าส วนประกอบและชน ดของคร มพ นม ผลอย างมากต อการปลดปล อยสารสาค ญจากส ตรตาร บ คาสาค ญ: ไนอาซ นาไมด คาเฟอ น ร ปแบบการปลดปล อย คร ม Abstract In Vitro Release Study of Niacinamide and Caffeine from Different Creams Jariyaporn Pumsakul 1 *, Sunee Channarong 1 The present study was to formulate and study the release of niacinamide (vitamin B 3 ) and caffeine from three different cream bases, vanishing cream, hydrophilic emulsion and cold cream. The releases of active components were evaluated using Franztype diffusion cells with artificial membrane. Both vanishing cream and hydrophilic emulsion are the same in o/w type with difference in emulsifying agent and oil components. The vanishing cream is more liquid than hydrophilic emulsion where as the cold cream is w/o type with the most inflexible. In vitro releases of niacinamide and caffeine from three cream bases showed the similar kinetics. Both niacinamide and caffeine showed the highest release amounts and the fastest rates in vanishing cream. The lowest release amounts and release rates were found in cold cream. The results of the study suggest that the components and types of cream bases strongly affect the release of the actives from the formulations. Keywords: Niacinamide, caffeine, release profile, cream, whitening 1 Faculty of Pharmaceutical Sciences, Huachiew Chalermprakiet University, Samut Prakan 100, Thailand Introduction Hyperpigmentation is a type of skin darkened by the over release of melanin by skin cells. It may cause from over exposure to the sun light, hormone imbalance, skin disorders 193 and post inflammation. Hyperpigmentation is commonly harmless but makes the skin unattractive. In case of post inflammation including acne, eczema and contact dermatitis, 193

2 the treatment challenging is reduction the hyperpigmentation without causing undesirable hypopigmentation and irritation (WooleryLlord, 011). A variety of topical whitening agents are available in inhibiting the different step of melanin production. The most commonly step is tyrosinase inhibitor. Hydroquinone has long been used as the gold standard of the treatment but the longterm use of hydroquinone risk to the hypopigmentation including irritation and erythema that finally leads to post inflammatory hyperpigmentation. However, the short term use of execute causes is still greatly effective. The newer whitening agents as alternative in long term use have been intensively investigated. Most of them are botanical origins such as kojic acid, arbutin, licorice, ascorbic acid and soy (Konda, 01). Niacinamide (Vitamin B 3 ) is a derivative of niacin which is one of the new whitening agents. Topical niacinamide showed benefits for post inflammatory form acne (Niren, 006). The reduced form of it might promise to act as antioxidant. Other benefits of niacinamide are the increase in collagen production, inhibitory of leucocyte peroxidase system of skin cells. Niacinamide also reduces sebum production (Bissett, 009). All of these effects showed the evidents to reduce the skin aging and acne (Lupo, 001). Niacinamide has been used in cosmeceutical products in concentrations ranging from 3..0% (Manela Azulay, 009). Caffeine is produced naturally by plants from coffee and tea. Applying caffeine on skin results the antiaging effect. In vitro test, caffeine shows the cell protective from UV radiation. Caffeine is cosmetically used in eye gels and cellulite burner due to the increase of micro circulation of skin blood vessels (Herman and Herman, 01). In this study, niacinamide and caffeine were combined to increase the efficacy of an alternative whitening preparation. Three different cream bases were prepared with %w/w of niacinamide and %w/w caffeine. The release profiles of niacinamide and caffeine were investigated to compare the topical characteristics. Material and methods 1. Materials Niacinamide was purchased from Chemico Inter Corporation Co., Ltd. Caffeine and sodium 1 heptanesulfonate were purchased from Fluka, Germany. 19 Methanol (HPLC grade) was purchased from Fisher Scientific. Other ingredients were pharmaceutical and cosmetic grade.. Formulation of niacinamide and caffeine creams Table 1 shows the ingredients of each formulation. To prepare hydrophilic emulsion, oil phase components (white beeswax, cetyl alcohol, almond oil and stearic acid) were mixed and heated to 70ºC. The water phase components (triethanolamine, propylene glycol, caffeine, methyl paraben and propyl paraben) were mixed and heated to 7ºC. After that, the aqueous phase was poured into the oil phase with homogenizer until it was cool. Vanishing cream and cold cream were prepared by melting white beeswax, stearic acid and mineral oil to 70ºC. The aqueous phase (sodium borate, glycerin (only in vanishing cream), methyl paraben, propyl paraben, caffeine and DI water) were mixed and heated to 7ºC. The aqueous phase was subsequently added into the oil phase with homogenizer until it was cool. In all cases, niacinamide was dissolved in sufficient quantity of DI water and poured into the emulsion while it was about ºC. 3. Drug release study The release studies were conducted using Franz diffusion cell (PermeGear, USA, 1 ml receptor volume), the membrane (Cellu Sep T1, MW cut off 300, Membrane Filtration Products, Inc USA) was saturated in phosphatebuffer (ph 7.) for hours and fitted into the place between two chambers. The receptor phase was phosphate buffer ph 7.. The temperature was maintained at 3±1 ºC. One gram of tested creams was mounted on the donor side of the Franz cell. Samples were withdrawn at different time intervals and were analyzed using HPLC. Each formulation was performed in triplicate.. Analysis of released niacinamide and caffeine The chromatographic analysis was conducted on an Inertsil ODS3 C18 (.6 mm 0 mm). The mobile phase consisted of 0.00 M sodium 1heptanesulfonate: HPLC grade methanol (70:30). The flow rate was set at 1.0 milliliter per minute and the detecting wavelength was set at nm. The volume for injection was 0 microliters. Calibration curves of niacinamide and caffeine were created by diluting from standard stock solutions and analyzed by HPLC. Correlation coefficient and linear regression equations were obtained by plots of concentration versus peak area. 19

3 . Viscosity measurements Viscosity measurements were performed at ±1ºC using Brookfield viscometer (DVII+, USA) with Tbar type spindle no. S9 at 1.0 rpm 6. ph measurements The ph meter was calibrated by standard buffer solution. About grams of each formulation was measured directly using the ph meter, at ±1ºC. Table 1. Components of the formulations Components Vanishing cream hydrophilic emulsion Cold cream Oil phase Cetyl alcohol White beeswax Mineral oil Stearic acid Almond oil Water phase Propylene glycol Glycerin Triethanolamine Sodium borate Methyl paraben Propyl paraben Caffeine Niacinamide DI water Results Niacinamide and caffeine are water soluble they readily release through the membrane within one hour. Figure 1 shows release profiles of niacinamide (A) and caffeine (B) from different creams rang in order of vanishing cream > hydrophilic emulsion > cold cream. Figure 1. Cumulative amounts (mg) of niacinamide (A) and caffeine (B) released from different creams

4 Table demonstrates the characteristics of the niacinamide and caffeine creams. The release fluxes through membrane from all formulations are shown. The ph values are 7.09, 7.8 and 6.61 for vanishing cream, hydrophilic emulsion and cold cream, respectively. The viscosity is directly related to the components of the formulation. As the results, cold cream is more viscous than vanishing cream about times. Table. Release fluxes in h, viscosity and ph values of different cream bases Cream base Flux of niacinamide (mcg/cm /h) Flux of caffeine (mcg/cm /h) ph Viscosity (cps) Vanishing cream 377.1± ± Hydrophilic emulsion 196.1± ± Cold cream 3.3 ±0..3 ± Table 3 and Table demonstrate the parameters and correlation coefficients obtained from kinetic equations calculated from the steady state regions ( h for vanishing cream and hydrophilic emulsion and 3 h for cold cream). The release data of both drugs from vanishing cream obeys Zero order kinetic, which their rate limiting step of the release is likely diffusion through the cream base. On the contrary, the release data of both drugs from cold cream follows Higuchi equation with R of and for niacinamide and caffeine, respectively. The release kinetics of both drugs from hydrophilic emulsion are anomalous and reveals the low R of all models. Various factors might be involved on the release of both drugs. The solubility of niacinamide and caffeine in the outer phase of emulsion as well as the water content in the formulation which strongly influence the thermodynamic activity of each drug. The types and concentrations of emulsifiers used in the formulations have been studied and were found to affect the drug releases. Table 3. In vitro release kinetics of niacinamide from different cream bases (n=3) Cream base Zero order First order Higuchi model k R k R k R Vanishing cream hydrophilic emulsion Cold cream Table. In vitro release kinetics of caffeine from different cream bases (n = 3) Cream base Zero order First order Higuchi model k R k R k R Vanishing cream hydrophilic emulsion Cold cream

5 Conclusion In this study, three creams were formulated with %w/w niacinamide and %w/w caffeine for whitening and firming aspects. On the basis of the release studies it was found that the different cream bases system remarkably altered the release of both ingredients. In case of vanishing cream, the highest amounts of both niacinamide and caffeine were detected, while cold cream provided the least extent of both niacinamide and caffeine due to the low solubility in the semisolid matrix. The release studies suggested that different cream bases obviously affect the drug distribution in the dosage form, drug release and might subsequently affect the absorption through skin after application. References Bissett DL. Common cosmeceuticals. Clin Dermatol 009; 7: 3. Herman A, Herman AP. Caffeine's mechanisms of action and its cosmetic use. Skin Pharmacol Physiol 01; 6(1): 81. Konda S, Geria AN, Halder RM. New horizons in treating disorders of hyperpigmentation in skin of color. Semin Cutan Med Surg 01; 31: Lupo MP. Antioxidants and Vitamins in Cosmetics. Clin Dermatol 001; 19: ManelaAzulay M, Bagatin E. Cosmeceuticals vitamins. Clin Dermatol 009; 7, Niren NM. Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: A review Cutis 006; 77: WooleryLloyd H, Kammer JN. Treatment of hyperpigmentation. Semin Cutan Med Surg 011; 30: