Formulation of ascorbyl phosphate in cosmeceutical products

Abstract

People and especially women are forever searching for new and improved ways to alter the appearance of their skin. Skin can be prematurely aged by various environmental factors, including prolonged exposure to ultraviolet (UV) light (Brannon, 2007). The aging of skin is amongst other factors facilitated by the degradation of collagen in the connective tissue (Uitto, 1993:299–314) (as quoted by Fisher et al., 1997:1420). Vitamin C and its derivatives are known to have anti–oxidant, as well as collagen forming properties (Gibbon et al., 2005:82). Vitamin C is a water–soluble compound and highly unstable. By using vitamin C–salts or esters such as sodium ascorbyl phosphate the absorption of the API (active pharmaceutical ingredient) can be improved, when formulated in topical preparations. This is because of the esters being more stable and lipophilic than the original vitamin (Austria et al., 1997:795). Transdermal drug delivery has many advantages including bypassing hepatic metabolism and a reduction in side effects (Kydonieus et al., 2000:3). The main problem encountered with transdermal drug delivery is the barrier function of the skin, which assists the body in keeping foreign bodies, infections and UVR (ultraviolet radiation) out and it helps keeping water and other vital substances in the body (Rushmer et al., 1966:343). According to Shindo et al. (1994:123) there are significant amounts of natural vitamin C found in both the epidermis, as well as the dermis. The concentrations of vitamin C in the epidermis is however higher than in the dermis. Penetration of an API may be increased by making use of physical or chemical penetration enhancers. A relatively new carrier medium, used in this study, is Pheroid™ technology. The principle of action for this method of enhancement rests on the use of vesicular structures with no phospholipids or cholesterol (Grobler et al., 2008:283). Ten different creams were formulated during this study. These formulations included various concentrations of the API, varying polarities; and either Pheroid™ or non–Pheroid™ formulas. Concentrations ranged between 1 and 3% for the formulations. A 1%, 2% and 3% cream was formulated in both Pheroid™ and non–Pheroid™ batches. Furthermore, a 2% cream with more liquid paraffin in the formula, as well as a 2% cream with less liquid paraffin in the formula were formulated (also in both Pheroid™ and non–Pheroid? batches) in order to determine the effect of varying polarities of the formulations on the release and penetration of the API. Two placebo formulations were also prepared in order to determine the concentration of natural vitamin C found in the skin, which should be compensated for during diffusion studies. Furthermore, the aqueous solubility of the active ingredient was determined to be 6.14 mg/ml and the octanol–water partition coefficient (log P) of the drug was found to be –0.005. This indicated that the drug would struggle to penetrate the skin, because of the fact that it is not soluble in both oil and water, but penetration could be improved by the fact that the drug is so highly water–soluble (Naik et al., 2000:321). Diffusion studies (where polytetrafluoroethylene membranes were used) were done in order to determine if the API was released from the formulation. The membrane release studies were performed over a 6 h period and it was observed that the 2% non–Pheroid™ cream, with less liquid paraffin in the formula, was the formulation with the highest average percentage released (2.008%) after the 6 h. Secondly was the 1% Pheroid™ formula. It had release of 1.940% after 6 h. It was thought that the higher polarity in the 2% formulation would prevent the highly water soluble API from releasing from the formulation. The polarity of the cream was higher due to the increased amount of water in the formulation (Mitsui, 1997:343). Because of the high percentage of unionised species (99.37%) of the API, a certain degree of release was however expected (Barry, 2002:511). The vertical Franz cell diffusion studies, performed over 12 h, proved the 2% non–Pheroid™ formulation to be the cream with the highest average concentration (3.761 μg/cm2) diffused. The 1% non–Pheroid™ formulation (3.555 μg/cm2) was the formulation closest to the 2% non– Pheroid™ formulation’s value. The high diffusion rates of the formulations can be attributed to the 99.37% unionised species of the API. According to Barry (2002:511) the unionised species of an API is usually lipid soluble and can pass readily across the stratum corneum. Furthermore, it seemed that the formulations which contained a lower concentration of the API performed greater than the formulations with higher concentrations of the active. This could be because of increased stability of the formulations, with lower concentrations of the API. The formulation with the highest average concentration of vitamin C in the stratum corneumepidermis (0.457 μg/ml) was the 2% Pheroid™ formulation with less liquid paraffin in the formula. This formulation showed a higher polarity because of the higher amount of water in the formulation (Mitsui, 1997:343). According to Bickers (2010:22) this could have led to the largely unionised API’s penetration into the stratum corneum–epidermis, as this oil soluble species of the API have an affinity for the lipid rich membrane. The formulation with the highest average concentration of vitamin C in the epidermis–dermis was the 1% Pheroid™ formulation, with an average value of 0.656 ?g/ml followed by the 2% Pheroid™ formula with a concentration of 0.530 μg/ml. This could be because of the API being entrapped in the Pheroid™ and thus having an improved lipid solubility (Grobler et al., 2008:297). According to the experimental data the 1% Pheroid™ cream was the formulation which performed the best overall during the experiments. It was the formulation with the second highest average percentage (1.940%) API released, after a period of 6 h, after the membrane release studies and the 4th highest concentration (3.057 μg/cm2) of API, after skin diffusion over 12 h. This formulation was also found to be the cream which penetrated the epidermis–dermis (target site) the best to yield an average API concentration of 0.656 μg/ml, which could be ascribed to the Pheroid™ in the formulation. Pheroid™ encapsulated the API molecules and helped increase the penetration of the drug through the stratum corneum and into the dermis (Grobler et al. 2008:297).