| Peer-Reviewed

A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives

Received: 23 July 2023    Accepted: 14 August 2023    Published: 6 September 2023
Views:       Downloads:
Abstract

The last two decades have seen an increase in active-led skin care products in over the counter and retail market places. Consumers have become more knowledgeable about ingredients used in topical products resulting in formulations with vitamins and other active ingredients gaining popularity. Further, the need for instantaneous and short-term benefits, consumers are moving towards high doses of active products. This poses a challenge for formulation scientists to stabilize high active doses and ensure potency over shelf life. Vitamin C or ascorbic acid is one such ubiquitous active commonly found in topical products claiming brightening, skin firming and toning benefits. As humans lack the enzyme required for synthesis of Vitamin C, we obtain it through diet or topical application. Vitamin C consumption results in insignificant benefits due to limited bioavailability, making topical application the major route of delivery. Ascorbic acid is an antioxidant; when applied topically it protects the skin from damaging free radicals produced due to exposure to UV-rays and other environmental stressors. However, ascorbic acid has been reported to be unstable in aqueous systems and readily undergoes oxidation making it inactive. This has led to the generation of multiple pro-drugs and derivatives which dissociate to release free ascorbic acid or its ionic form in the skin. In this review, we have focused on the clinical efficacy of vitamin C and its derivatives, suitable for various applications. This will serve as a ready reckoner for formulators creating vitamin C based products.

Published in Pharmaceutical Science and Technology (Volume 7, Issue 2)
DOI 10.11648/j.pst.20230702.11
Page(s) 20-26
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Ascorbic Acid, Vitamin C, Antioxidant, Depigmentation, Ethyl Ascorbic Acid, Ascorbyl Glucoside

References
[1] A. C. Caritá, B. Fonseca-Santos, J. D. Shultz, B. Michniak-Kohn, M. Chorilli, and G. R. Leonardi, “Vitamin C: One compound, several uses. Advances for delivery, efficiency and stability,” Nanomedicine Nanotechnol. Biol. Med., vol. 24, p. 102117, Feb. 2020, doi: 10.1016/j.nano.2019.102117.
[2] P. K. Farris, “Topical Vitamin C: A Useful Agent for Treating Photoaging and Other Dermatologic Conditions,” Dermatol. Surg., vol. 31, pp. 814–818, Mar. 2006, doi: 10.1111/j.1524-4725.2005.31725.
[3] P. Telang, “Vitamin C in dermatology,” Indian Dermatol. Online J., vol. 4, no. 2, p. 143, 2013, doi: 10.4103/2229-5178.110593.
[4] S. Ravetti, C. Clemente, S. Brignone, L. Hergert, D. Allemandi, and S. Palma, “Ascorbic Acid in Skin Health,” Cosmetics, vol. 6, no. 4, p. 58, Oct. 2019, doi: 10.3390/cosmetics6040058.
[5] S. R. Pinnell, H. Yang, M. Omar, N. M. Riviere, H. V. DeBuys, L. C. Walker, Y. Wang, and M. Levine, “Topical L-Ascorbic Acid: Percutaneous Absorption Studies.” Dermatol Surg, vol. 27, p. 137-142, 2001, doi: 10.1046/j.1524-4725.2001.00264.
[6] Y. C. Boo, “Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes: Emerging Combination Therapies,” Antioxidants, vol. 11, no. 9, p. 1663, Aug. 2022, doi: 10.3390/antiox11091663.
[7] K. Lintner, F. Gerstein, and N. Solish, “A serum containing vitamins C & E and a matrix-repair tripeptide reduces facial signs of aging as evidenced by Primos® analysis and frequently repeated auto-perception,” J. Cosmet. Dermatol., vol. 19, no. 12, pp. 3262–3269, Dec. 2020, doi: 10.1111/jocd.13770.
[8] S.-W Hwang, D.-J. Oh, D. Lee, J.-W. Kim, and S.-W. Park, “Clinical Efficacy of 25% l-Ascorbic Acid (C’ensil) in the Treatment of Melasma,” J. Cutan. Med. Surg., vol. 13, no. 2, pp. 74–81, Mar. 2009, doi: 10.2310/7750.2008.07092.
[9] F. Iliopoulos, B. C. Sil, D. J. Moore, R. A. Lucas, and M. E. Lane, “3-O-ethyl-l-ascorbic acid: Characterisation and investigation of single solvent systems for delivery to the skin,” Int. J. Pharm. X, vol. 1, p. 100025, Dec. 2019, doi: 10.1016/j.ijpx.2019.100025.
[10] I. Golonka, M. Oleksy, A. Junka, A. Matera-Witkiewicz, M. Bartoszewicz, and W. Musiał, “Selected Physicochemical and Biological Properties of Ethyl Ascorbic Acid Compared to Ascorbic Acid,” Biol. Pharm. Bull., vol. 40, no. 8, pp. 1199–1206, 2017, doi: 10.1248/bpb.b16-00967.
[11] N. Zerbinati, S. Sommatis, C. Maccario, S. D. Francesco, M. C. Capillo, R. Rauso, M. Herrera, P. L. Bencini, S. Guida, and R. Mocchi, “The Anti-Ageing and Whitening Potential of a Cosmetic Serum Containing 3-O-ethyl-l-ascorbic Acid,” Life, vol. 11, no. 5, Art. no. 5, May 2021, doi: 10.3390/life11050406.
[12] P. Špiclin, M. Homar, A. Zupančič-Valant, and M. Gašperlin, “Sodium ascorbyl phosphate in topical microemulsions,” Int. J. Pharm., vol. 256, no. 1, pp. 65–73, Apr. 2003, doi: 10.1016/S0378-5173(03)00063-2.
[13] X. Dong, T. Zhang, H. Wei, and L. Dang, “Stability of sodium ascorbyl phosphate in the water-glycerol system,” J. Pharm. Biomed. Anal., vol. 181, p. 113103, Mar. 2020, doi: 10.1016/j.jpba.2020.113103.
[14] S. Mohammadi, J. Shokri, M. Ranjikesh, S. A. Hamed, and F. Monajjemzadeh, “Comparative physicochemical stability and clinical anti-wrinkle efficacy of transdermal emulgel preparations of 5% sodium ascorbyl phosphate and or ascorbic acid on human volunteers’’ J. Cosmetic Dermatology, Apr. 2020, doi-10.1111/jocd.13471.
[15] J. Klock, H. Ikeno, K. Ohmori, T. Nishikawa, J. Vollhardt, and V. Schehlmann, “Sodium ascorbyl phosphate shows in vitro and in vivo efficacy in the prevention and treatment of acne vulgaris,” Int. J. Cosmet. Sci., vol. 27, no. 3, pp. 171–176, 2005, doi: 10.1111/j.1467-2494.2005.00263.x.
[16] M. Naeem, “Synergistic effects of ascorbyl palmitate and sodium ascorbyl phosphate loaded in multiple emulsions on facial skin melanin and erythema content,” Biomed. Res., vol. 27, no. 2, pp. 570-576, Apr. 2016.
[17] R. Austria, A. Semenzato, and A. Bettero, “Stability of vitamin C derivatives in solution and topical formulations,” J. Pharm. Biomed. Anal., vol. 15, no. 6, pp. 795–801, Mar. 1997, doi: 10.1016/S0731-7085(96)01904-8.
[18] A. I. Segall and M. A. Moyano, “Stability of vitamin C derivatives in topical formulations containing lipoic acid, vitamins A and E,” Int. J. Cosmet. Sci., vol. 30, no. 6, pp. 453–458, 2008, doi: 10.1111/j.1468-2494.2008.00473.x.
[19] P. M. B. G. Maia Campos, G. M. S. Gonçalves, and L. R. Gaspar, “In vitro antioxidant activity and in vivo efficacy of topical formulations containing vitamin C and its derivatives studied by non-invasive methods,” Skin Res. Technol., vol. 14, no. 3, pp. 376–380, 2008, doi: 10.1111/j.1600-0846.2008.00288.x.
[20] K. Kameyama, C. Sakai, S. Kondoh, K. Yanemoto, S. Nishiyama, M. Tagawa, T. Murata, T. Ohnuma, J. Quigley, A. Dorsky, D. Bucks, and K. Blanock, “Inhibitory effect of magnesium l-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo,” J. Am. Acad. Dermatol., vol. 34, no. 1, pp. 29–33, Jan. 1996, doi: 10.1016/S0190-9622(96)90830-0.
[21] W.-Y. Huang, P.-C. Lee, L.-K. Huang, L.-P. Lu, and W. C. Liao, “Stability studies of ascorbic acid 2-glucoside in cosmetic lotion using surface response methodology,” Bioorg. Med. Chem. Lett., vol. 23, no. 6, pp. 1583–1587, Mar. 2013, doi: 10.1016/j.bmcl.2013.01.111.
[22] J. Takebayashi, A. Tai, E. Gohda, and I. Yamamoto, “Characterization of the Radical-Scavenging Reaction of 2-O-Substituted Ascorbic Acid Derivatives, AA-2G, AA-2P, and AA-2S: A Kinetic and Stoichiometric Study,” Biol. Pharm. Bull., vol. 29, no. 4, pp. 766–771, 2006, doi: 10.1248/bpb.29.766.
[23] Y. Kumano, T. Sakamoto, M. Egawa, I. Iwai, M. Tanaka, and I. Yamamoto, “In Vitro and In Vivo Prolonged Biological Activities of Novel Vitamin C Derivative, 2-O-α-D-Glucopyranosyl-L-Ascorbic Acid (AA-2G), in Cosmetic Fields,” J. Nutr. Sci. Vitaminol. (Tokyo), vol. 44, no. 3, pp. 345–359, 1998, doi: 10.3177/jnsv.44.345.
[24] I. Yamamoto and N. Muto, “Bioavailability and Biological Activity of L-Ascorbic Acid 2-O-α-Glucoside,” J. Nutr. Sci. Vitaminol. (Tokyo), vol. 38, no. Special, pp. 161–164, 1992, doi: 10.3177/jnsv.38.Special_161.
[25] M. Kouki, M. Norio, F. Kyoko, and Y. Itaru, “Comparison of ascorbic acid and ascorbic acid 2-O-α-glucoside on the cytotoxicity and bioavailability to low density cultures of fibroblasts,” Biochem. Pharmacol., vol. 44, no. 11, pp. 2191–2197, Dec. 1992, doi: 10.1016/0006-2952(92)90346-K.
[26] N. J. Starr, K. A. Hamid, J. Wibawa, I. Marlow, M. Bell, L. P. Garcia, D. A. Barrett, and D. J. Scurr, “Enhanced vitamin C skin permeation from supramolecular hydrogels, illustrated using in situ ToF-SIMS 3D chemical profiling,” Int. J. Pharm., vol. 563, pp. 21–29, May 2019, doi: 10.1016/j.ijpharm.2019.03.028.
[27] N. P. J. Stamford, “Stability, transdermal penetration, and cutaneous effects of ascorbic acid and its derivatives,” J. Cosmet. Dermatol., vol. 11, no. 4, pp. 310–317, 2012, doi: 10.1111/jocd.12006.
[28] P. Jurkovič, M. Šentjurc, M. Gašperlin, J. Kristl, and S. Pečar, “Skin protection against ultraviolet induced free radicals with ascorbyl palmitate in microemulsions,” Eur. J. Pharm. Biopharm., vol. 56, no. 1, pp. 59–66, Jul. 2003, doi: 10.1016/S0939-6411(03)00062-6.
[29] A. Meves, S. N. Stock, A. Beyerle, M. R. Pittelkow, and D. Peus, “Vitamin C Derivative Ascorbyl Palmitate Promotes Ultraviolet-B-Induced Lipid Peroxidation and Cytotoxicity in Keratinocytes,” J. Invest. Dermatol., vol. 119, no. 5, pp. 1103–1108, Nov. 2002, doi: 10.1046/j.1523-1747.2002.19521.x.
[30] Ü. Gönüllü, G. Yener, M. Üner, and T. Incegül, “Moisturizing potentials of ascorbyl palmitate and calcium ascorbate in various topical formulations,” Int. J. Cosmet. Sci., vol. 26, no. 1, pp. 31–36, 2004, doi: 10.1111/j.0142-5463.2004.00202.x.
[31] R. E. Fitzpatrick and E. F. Rostan, “Double-Blind, Half-Face Study Comparing Topical Vitamin C and Vehicle for Rejuvenation of Photodamage,” Dermatol. Surg., vol. 28, no. 3, pp. 231–236, 2002, doi: 10.1046/j.1524-4725.2002.01129.x.
[32] W. R. Swindell, M. Randhawa, G. Quijas, K. Bojanowski, and R. K. Chaudhuri, “Tetrahexyldecyl Ascorbate (THDC) Degrades Rapidly under Oxidative Stress but Can Be Stabilized by Acetyl Zingerone to Enhance Collagen Production and Antioxidant Effects,” Int. J. Mol. Sci., vol. 22, no. 16, Art. no. 16, Jan. 2021, doi: 10.3390/ijms22168756.
[33] L. Xiao. K. Kaneyasu, Y. Saitoh, Y. Terashima, Y. Kowata, and N. Miwa, “Cytoprotective effects of the lipoidic-liquiform pro-vitamin C tetra-isopalmitoyl-ascorbate (VC-IP) against ultraviolet-A ray-induced injuries in human skin cells together with collagen retention, MMP inhibition and p53 gene repression’’ J. Cellular Biochem, vol 106, pp. 589-598, Jan 2009, doi: 10.1002/jcb.22032.
[34] A. Hinek, H. J. Kim, Y. Wang, A. Wang, and T. F. Mitts, “Sodium l-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin,” J. Dermatol. Sci., vol. 75, no. 3, pp. 173–182, Sep. 2014, doi: 10.1016/j.jdermsci.2014.05.011.
[35] A. Pielesz, C. Ślusarczyk, D. Biniaś, and R. Bobiński, “Sodium ascorbate (SA) and l-ascorbic acid (AA) as modifiers of burn affected skin – A comparative analysis,” Spectrochim. Acta. A. Mol. Biomol. Spectrosc., vol. 209, pp. 55–61, Feb. 2019, doi: 10.1016/j.saa.2018.10.021.
[36] U. Gönüllü, D. Sensoy, M. Uner, G. Yener, and T. Altinkurt, “Comparing the moisturizing effects of ascorbic acid and calcium ascorbate against that of tocopherol in emulsions,” J. Cosmet. Sci., vol. 57, no. 6, pp. 465–473, Nov. 2006.
Cite This Article
  • APA Style

    Oormila Sasidharan, Anjali Gholap, Rachna Rastogi. (2023). A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives. Pharmaceutical Science and Technology, 7(2), 20-26. https://doi.org/10.11648/j.pst.20230702.11

    Copy | Download

    ACS Style

    Oormila Sasidharan; Anjali Gholap; Rachna Rastogi. A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives. Pharm. Sci. Technol. 2023, 7(2), 20-26. doi: 10.11648/j.pst.20230702.11

    Copy | Download

    AMA Style

    Oormila Sasidharan, Anjali Gholap, Rachna Rastogi. A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives. Pharm Sci Technol. 2023;7(2):20-26. doi: 10.11648/j.pst.20230702.11

    Copy | Download

  • @article{10.11648/j.pst.20230702.11,
      author = {Oormila Sasidharan and Anjali Gholap and Rachna Rastogi},
      title = {A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives},
      journal = {Pharmaceutical Science and Technology},
      volume = {7},
      number = {2},
      pages = {20-26},
      doi = {10.11648/j.pst.20230702.11},
      url = {https://doi.org/10.11648/j.pst.20230702.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.pst.20230702.11},
      abstract = {The last two decades have seen an increase in active-led skin care products in over the counter and retail market places. Consumers have become more knowledgeable about ingredients used in topical products resulting in formulations with vitamins and other active ingredients gaining popularity. Further, the need for instantaneous and short-term benefits, consumers are moving towards high doses of active products. This poses a challenge for formulation scientists to stabilize high active doses and ensure potency over shelf life. Vitamin C or ascorbic acid is one such ubiquitous active commonly found in topical products claiming brightening, skin firming and toning benefits. As humans lack the enzyme required for synthesis of Vitamin C, we obtain it through diet or topical application. Vitamin C consumption results in insignificant benefits due to limited bioavailability, making topical application the major route of delivery. Ascorbic acid is an antioxidant; when applied topically it protects the skin from damaging free radicals produced due to exposure to UV-rays and other environmental stressors. However, ascorbic acid has been reported to be unstable in aqueous systems and readily undergoes oxidation making it inactive. This has led to the generation of multiple pro-drugs and derivatives which dissociate to release free ascorbic acid or its ionic form in the skin. In this review, we have focused on the clinical efficacy of vitamin C and its derivatives, suitable for various applications. This will serve as a ready reckoner for formulators creating vitamin C based products.},
     year = {2023}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - A Review of Clinical Efficacy of Topical Vitamin C and Its Derivatives
    AU  - Oormila Sasidharan
    AU  - Anjali Gholap
    AU  - Rachna Rastogi
    Y1  - 2023/09/06
    PY  - 2023
    N1  - https://doi.org/10.11648/j.pst.20230702.11
    DO  - 10.11648/j.pst.20230702.11
    T2  - Pharmaceutical Science and Technology
    JF  - Pharmaceutical Science and Technology
    JO  - Pharmaceutical Science and Technology
    SP  - 20
    EP  - 26
    PB  - Science Publishing Group
    SN  - 2640-4540
    UR  - https://doi.org/10.11648/j.pst.20230702.11
    AB  - The last two decades have seen an increase in active-led skin care products in over the counter and retail market places. Consumers have become more knowledgeable about ingredients used in topical products resulting in formulations with vitamins and other active ingredients gaining popularity. Further, the need for instantaneous and short-term benefits, consumers are moving towards high doses of active products. This poses a challenge for formulation scientists to stabilize high active doses and ensure potency over shelf life. Vitamin C or ascorbic acid is one such ubiquitous active commonly found in topical products claiming brightening, skin firming and toning benefits. As humans lack the enzyme required for synthesis of Vitamin C, we obtain it through diet or topical application. Vitamin C consumption results in insignificant benefits due to limited bioavailability, making topical application the major route of delivery. Ascorbic acid is an antioxidant; when applied topically it protects the skin from damaging free radicals produced due to exposure to UV-rays and other environmental stressors. However, ascorbic acid has been reported to be unstable in aqueous systems and readily undergoes oxidation making it inactive. This has led to the generation of multiple pro-drugs and derivatives which dissociate to release free ascorbic acid or its ionic form in the skin. In this review, we have focused on the clinical efficacy of vitamin C and its derivatives, suitable for various applications. This will serve as a ready reckoner for formulators creating vitamin C based products.
    VL  - 7
    IS  - 2
    ER  - 

    Copy | Download

Author Information
  • Bregma Science LLP, Bangalore, India

  • Bregma Science LLP, Bangalore, India; DPKA Universal Consumer Ventures Private Limited, Mumbai, India

  • Bregma Science LLP, Bangalore, India; DPKA Universal Consumer Ventures Private Limited, Mumbai, India

  • Sections