Finding
Topical ascorbic acid treatment for skin disorders [20].
Paper
Complexed Ascorbic Acid for Topical Applications
Abstract
Ascorbic acid (vitamin C, AA) has found legendary applications in topical and skin antiaging products. The stability of AA in aqueousbased formulations in the presence of light, heat, and air has posed significant consumer and marketing concerns. A number of approaches, from the entrapment or encapsulation of AA to its derivatization, have been reported. The relative efficacy, availability, and cost viability of these routes have yet to provide a universally acceptable solution. The most direct approach, the stabilization of AA itself in water-based formulations with the inclusion of alkali metal bicarbonate, is reported herein. The chemical mechanism of this stabilization remains unknown. Citation: Peter D, Stanek J, Wochner M, Gupta S. Complexed Ascorbic Acid for Topical Applications. J Clin Investigat Dermatol. 2016;4(1): 4. J Clin Investigat Dermatol 4(1): 4 (2016) Page 02 ISSN: 2373-1044 to a tautomeric isomerization. AA esters with the longer acyl chain (C-16, C-14 and C-12) have exhibited good surfactant activity [39]. The surfactant activity, extraneous to AA’s antioxidant property, may not be a desirable attribute in certain topical compositions from efficacy and drug safety considerations. For example, 6-O-Ascorbic acid alkanoates are amphiphilic molecules having physical-chemical properties that depend on the alkyl chain length. Longer length of the hydrophobic chain can turn these into either micellar solutions or gel phases, which can enhance the penetration of other constituents present in the same composition into skin. In practical terms, certain ascorbyl esters have been noted to enhance skin penetration of vitamin E and other lipophilic agents (topical ibuprofen, for example) that may be copresent in a water-based formulation [40,41]. Additionally, the comparative in vivo antioxidant efficacy of ascorbic acid and its ester or other derivatives is relatively unknown. The stability issue has received more focus than their relative efficacy, accessibility, or cost viability parameters in formulating AA derivatives. On theoretical basis alone, the two free hydrogen atoms bonded to C=C bond in AA can be utilized in the capture of free radicals to provide antioxidant benefits (Figure 1) [42]. This would indicate that, in comparison to itself, any esters or derivatives of AA that have one or both of these functional -OH groups blocked may have a compromised antioxidant activity. However, any such comparative data on a molar equivalence basis seem not to exist. It appears that the esters of AA may be hydrolyzing in vivo to release AA, which then provides the antioxidant action [43]. To illustrate this further, calculated molar equivalents of select AA derivatives are noted in Table 3. This could indicate the relative amounts of AA esters required to deliver equivalent antioxidant benefit, as per the above AA ester hydrolysis theory. Resolutive research is required. The examples noted above bring to focus the complexity of AA stabilization via encapsulation and derivatization methods. Formulating AA itself in stabilized topical products offers a most direct, cost viable, easily accessible, and possibly most efficacious route. Keep it Simple & Safe (KISS): this philosophy of formulating consumer-preferred products has resulted in a very simple method for stabilized AA. It has now been discovered that the inclusion of alkali metal bicarbonates in aqueous-based formulations provides stabilized AA. The use of alkali metal carbonates and hydroxides via identical methodology results in unstable formulations [44]. It is worthy of note that sodium ascorbate, made from AA and sodium bicarbonate, is also unstable [44]. Sodium ascorbate, in a solid form, does not suffer from such instability. The reason for unexpected stability of AA/ bicarbonate/water system reported herein is not known. Figure 1: Antioxidant mechanism of ascorbic acid [42]. 1. Topical ascorbic acid on photoaged skin [2]. 2. Ascorbic Acid for the safe use of a sunscreen agent [3]. 3. Split-face study of topical 23.8% L-ascorbic acid serum in treating photo-aged skin [4]. 4. The study of absorption efficiency and restoring effects of collagen and ascorbic acid on aged skin [5]. 5. Induction of collagen synthesis by ascorbic acid [6,7]. 6. Ascorbic acid enhances the expression of collagen in human skin fibroblasts [8]. 7. The effects of topical l(+) lactic Acid and ascorbic Acid on skin whitening [9]. 8. Ascorbic acid for the healing of skin wounds [10]. 9. The role of vitamin C in pushing back the boundaries of skin aging [11]. 10. Split-face vitamin C consumer preference study [12]. 11. Improved scar appearance with combined use of silicone gel and vitamin C [13]. 12. Vitamin C possesses benefits including protection from UV A & B, neocollagenesis, inhibition of melanogenesis and improvement of inflammatory skin disorders [14]. 13. Use of topical nanosome vitamin C iontophoresis in the treatment of melasma [15]. 14. Sodium L-ascorbyl-2-phosphate for the treatment of acne vulgaris [16]. 15. The cosmetic treatment of wrinkles [17]. 16. Ascorbic acid causes reduction of oxidative stress, improvement of the epidermal-dermal microstructure and reduction of fine lines and wrinkles in aged skin [18]. 17. Sodium ascorbate elastogenesis [19]. 18. Topical ascorbic acid treatment for skin disorders [20]. 19. Anti-wrinkle Effect of Ascorbic Acid [21]. Table 1: Topical applications of ascorbic acid. Citation: Peter D, Stanek J, Wochner M, Gupta S. Complexed Ascorbic Acid for Topical Applications. J Clin Investigat Dermatol. 2016;4(1): 4. J Clin Investigat Dermatol 4(1): 4 (2016) Page 03 ISSN: 2373-1044 Materials and Methods Preparation of samples for stability testing All weights are in weight %. Temperatures are in °C. Example 1: Preparation of Ascorbic Acid (25%) and Water with Additional Ingredients (Control Sample for stability). Ingredients: (1) Water 68.49 (2) Ascorbic acid, 25.00 (3) Beta Fructan 0.05 (4) Glucosamine hydrochloride 0.05 (5) Red wine concentrate 0.01 (6) Preservative 1.1 (7) Potassium sorbate 0.05 (8) Hydrolite-5 5.00 (9) Amigum 0.25. Processing: The preparative methodology has been reported elsewhere [44]. Example 2: Preparation of the Complex of Ascorbic Acid (25%) and Sodium Bicarbonate with Additional Ingredients. Ingredients: (1) Water 56.56 (2) Ascorbic acid, 25.00 (3) Sodium bicarbonate 11.93 (4) Beta Fructan 0.05 (5) Glucosamine hydrochloride 0.05 (6) Red wine concentrate 0.01 (7) Preservative 1.1 (8) Potassium sorbate 0.05 (9) Hydrolite-5 5.00 (10) Amigum 0.25. Processing: The preparative methodology has been reported elsewhere [44]. Example 3: Preparation of the complex of Ascorbic Acid (25%) and Sodium Carbonate (1:1 molar ratio) with Additional Ingredients. Ingredients: (1) Water 53.45 (2) Ascorbic acid, 25.00 (3) Sodium carbonate 15.04 (4) Beta Fructan 0.05 (5) Glucosamine hydrochloride 0.05 (6) Red wine concentrate 0.01 (7) Preservative 1.1 (8) Potassium sorbate 0.05 (9) Hydrolite-5 5.00 (10) Amigum 0.25. Processing: The preparative methodology has been reported elsewhere [44]. Example 4: Preparation of Ascorbic Acid (25%) and Sodium Hydroxide with Additional Ingredients. Ingredients: (1) Water 40.09 (2) Ascorbic acid, 25.00 (3) Sodium Hydroxide (20% solution) 28.40 (4) Beta Fructan 0.05 (5) Glucosamine hydrochloride 0.05 (6) Red wine concentrate 0.01 (7) Preservative 1.1 (8) Potassium sorbate 0.05 (9) Hydrolite-5 5.00 (10) Amigum 0.25. Processing: The preparative methodology has been reported elsewhere. Stability testing of samples from examples 1 to 4 Procedure: The samples of examples 1 to 4 are stored at room temperature and also at 40 °C in a container having air space on the top for a period of time. USP Ascorbic Acid Injection Method (ACCU Labs test method C-015) was used to determine ascorbic acid content. Any changes in color or pH were also recorded. These data are summarized in Table 2. Results and Discussion The data in Table 2 clearly show the stability of AA formulations in aqueous media in the presence of alkali metal bicarbonate, even with the inclusion of other skin beneficial agents and processing aids. AA formulations in aqueous media with alkali metal carbonates or hydroxides were unstable under comparative conditions. Conclusion Formulation of AA in combination with alkali metal bicarbonate in water-based systems provides heat, light, and air stable compositions. This offers a simple solution to stability concerns relative to AA-based formulations. Ascorbic acid is thus now available for a plethora of topical applications reported in Table 1. References 1. England S, Seifter S (1986) The biochemical functions of ascorbic acid. Ann Rev Nutri 6: 365-406. 2. Humbert PG, Haftek M, Creidi P, Lapière C, Nusgens B, et al. (2003) Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo. Exp Dermatol 12: 237-244. 3. Fathi-azarbayjani A, Tan PL, Chan YY, Chan SY (2013) Ascorbic acid for the safe use of a sunscreen agent: accumulation of nano zinc oxide and titanium dioxide on the skin. Sci Pharm 81: 1141-1150. 4. Xu TH, Chen JZ, Li YH, Wu Y, Luo YJ, et al. (2012) Split-face study of topical 23.8% L-ascorbic acid serum in treating photo-aged skin. J Drugs Dermatol 11: 51-56. 5. Zhang Y, Jia YH, Chen JW, Liu Y, Shen XJ, et al. (2012) Application progress of laser-induced breakdown spectroscopy for surface analysis in materials science field. Guang Pu Xue Yu Guang Pu Fen Xi 32: 1441-1446. 6. Kitt DQ (2016) Arterial Tortuosity Syndrome reveals function of dehydroascorbic acid in collagen and elastin synthesis: implications for skin care. Med Hypotheses 87: 8-9. 7. Pinnel SR, Murad S, Darr D (1987) Induction of collagen synthesis by ascorbic acid. A possible mechanism. Arch Dermatol 123: 1684-1686. 8. Kishimoto Y, Saito N, Kurita K, Shimokado K, Maruyama N, et al. (2013) Ascorbic acid enhances the expression of type 1 and type 4 collagen and SVC
Authors
D. Peter, M. Wochner, S. Gupta
Journal
Journal name not available for this finding