A PEEL-OFF FACE MASK GEL CONTAINING SILYMARIN FOR THE MANAGEMENT OF FACIAL ACNE: FORMULATION AND OPTIMISATION BY RESPONSE SURFACE METHODOLOGY APPROACH

SINDHOOR S. M.; GLADYSTON NETTO; VAISHNAVI; SILNA SASI; SHARMA ABHISHEK RAMVRIKSH

doi:10.22159/ijap.2025v17i6.55416

Authors

SINDHOOR S. M. Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutics, Mangalore, India https://orcid.org/0000-0003-3937-9858
GLADYSTON NETTO Dr. D. Y. Patil Unitech Society’s, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India. Dr. D. Y. Patil Dnyan Prasad University, School of Pharmacy and Research, Pimpri, Pune, India https://orcid.org/0000-0002-5829-8538
VAISHNAVI Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutics, Mangalore, India https://orcid.org/0009-0003-9941-7622
SILNA SASI Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutics, Mangalore, India https://orcid.org/0009-0006-9318-9982
SHARMA ABHISHEK RAMVRIKSH Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutics, Mangalore, India https://orcid.org/0009-0006-4400-1277

DOI:

https://doi.org/10.22159/ijap.2025v17i6.55416

Keywords:

Silymarin, Peel off face mask gel, Box behnken design, Antioxidant, Facial acne

Abstract

Objective: To prepare and optimise peel-off face mask gel containing silymarin for the management of acne and evaluate its performance in vitro.

Methods: This study established Silymarin's identity using Proton NMR and FTIR. A total of 17 peel-off facemask gels containing silymarin were subsequently prepared as per Box Behnken Design and the influence of the formulation components on the critical evaluation parameters was investigated. The optimised formulation was selected based on criteria of maximum spreadability and minimum drying time. The optimised formulation was then subjected to various in vitro evaluation parameters like organoleptic properties, Physiochemical properties, antioxidant activity, antimicrobial activity and stability studies.

Results: Statistical analysis from the Box Behnken Design (BBD) revealed that ethanol concentration had a significant inverse relationship with drying time (coefficient: –5.56, p<0.0001), while PVA and Carbopol negatively influenced spreadability (p<0.0001). The optimized formulation, containing 6.01% PVA, 0.632% Carbopol, and 8.3% ethanol, exhibited a drying time of 22.56 min and spreadability of 4.25 cm, with a residual error of 5.15% for drying time and 3.19% for spreadability from predicted values and overall desirability of 0.925. The formulation showed desirable organoleptic properties, a viscosity of 7700±435.88 cP, and a pH of 5.45±0.25, making the formulation suitable for topical application. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging activity confirmed the antioxidant potential of the peel-off facial mask with an IC 75 value of 525µg/ml. Antimicrobial studies showed a 22.1 mm zone of inhibition against S. aureus, comparable to standard clindamycin gel (23.4 mm). In vitro diffusion studies indicated a sustained drug release (68.1% at 24 h) with Korsmeyer–Peppas model fitting (R² = 0.981, n = 0.481), confirming diffusion-based release mechanism. Stability testing confirmed the formulation retained its key properties under room and accelerated conditions for 30 days.

Conclusion: The developed formulation satisfied all the in vitro evaluation criteria for peel-off face mask gels and has potent antioxidant and anti microbial potential. However, further in vivo studies of the formulation in suitable animal models are required to validate its therapeutic efficacy.

References

1. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012 Jan 28;379(9813):361-72. doi: 10.1016/S0140-6736(11)60321-8, PMID 21880356.

2. Thiboutot DM, Dreno B, Abanmi A, Alexis AF, Araviiskaia E, Barona Cabal MI. Practical management of acne for clinicians: an international consensus from the global alliance to improve outcomes in acne. J Am Acad Dermatol. 2018 Feb;78(2)Suppl 1:S1-S23.e1. doi: 10.1016/j.jaad.2017.09.078, PMID 29127053.

3. Griffiths C, Barker J, Bleiker T, Chalmers R, Creamer D. Neoplastic proliferative and infiltrative disorders affecting the skin part 12. In: Bewley A, Calonje E, Griffiths T, Jemec GB, Levell NJ, editors. Rook’s textbook of dermatology. 9th ed. Vol. 4. Chichester, UK: Wiley-Blackwell; 2016. p. 3620-67.

4. Rathi SK. Acne vulgaris treatment: the current scenario. Indian J Dermatol. 2011 Jan;56(1):7-13. doi: 10.4103/0019-5154.77543, PMID 21572783.

5. Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. “Silymarin,” a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011 Jul-Aug;14(4):308-17. PMID 23492971.

6. Atallah DA, Badran AY, Makhlouf AG, Mekkawy MM. Topical silymarin cream as a novel therapy versus salicylic acid peels in acne vulgaris: a split-face clinical trial. J Cutan Med Surg. 2024 Jan-Feb;28(1):22-8. doi: 10.1177/12034754231211568, PMID 37942562.

7. Salmannejad F, Qorab H, Ghari T. Formulation characterisation and optimisation of peel off gel of soybean extract as a face mask. Trop J Nat Prod Res. 2024;8(3):6544-51. doi: 10.26538/tjnpr/v8i3.11.

8. Zarwinda I, Fauziah F, Jumirna J, Adriani A. The formulation of peel off mask from the ethanol extract of bilimbi leaves (Averrhoa blimbi L.) as an anti-acne treatment. LJ. 2021;9(1):499035. doi: 10.22373/lj.v9i1.10206.

9. Baby AR, Zague V, Maciel CP, Salgado Santos IM, Kawano Y, Areas EP. Development of cosmetic mask formulations. Rev Bras Cienc Farm. 2004 Apr;40(2):159-61.

10. Nur S, Sami FJ, Sapra A, Aisyah AN, Burhan A, Megawati. Application box–behnken design for the optimum cream formula of Muntingia calabura fruit extract: in vitro and in vivo studies as an antiaging product. Res J Pharm Technol. 2024;17(11):5325-35. doi: 10.52711/0974-360X.2024.00815.

11. Alshehri FS, Kotb E, Nawaz M, Al Jameel S, Amin KA. Preparation, characterization and antibacterial competence of silymarin and its nano-formulation. J Exp Nanosci. 2022;17(1):100-12. doi: 10.1080/17458080.2022.2041192.

12. Rosaini H, Makmur I, Lestari EA, Sidoretno WM, Yetti RD. Formulation of gel peel-off catechins mask from gambir (Uncaria gambir (Hunter) Roxb) with the PVP K-30 concentration variation. Int J Res Rev. 2021;8(3):205-11.

13. Beringhs AO, Rosa JM, Stulzer HK, Budal RM, Sonaglio D. Green clay and aloe vera peel-off facial masks: response surface methodology applied to the formulation design. AAPS PharmSciTech. 2013 Jun;14(1):445-55. doi: 10.1208/s12249-013-9930-8.

14. Khullar R, Kumar D, Seth N, Saini S. Formulation and evaluation of mefenamic acid emulgel for topical delivery. Saudi Pharm J. 2012;20(1):63-7. doi: 10.1016/j.jsps.2011.08.001, PMID 23960777.

15. Syakri S, Ismail I, Amal NM, Masjidi NA, Tahir KA. Characterization and anti-aging tests of peel-off gel masks made from ethanolic extract of yarrow (Achillea millefolium). Maced J Med Sci. 2021 Oct 8;9(B):1156-61. doi: 10.3889/oamjms.2021.7574.

16. Naga Sravan Kumar Varma V, Maheshwari PV, Navya M, Reddy SC, Shivakumar HG, Gowda DV. Calcipotriol delivery into the skin as emulgel for effective permeation. Saudi Pharm J. 2014 Dec;22(6):591-9. doi: 10.1016/j.jsps.2014.02.007, PMID 25561873.

17. Anthony KP, Saleh MA. Free radical scavenging and antioxidant activities of silymarin components. Antioxidants (Basel). 2013 Sep;2(4):398-407. doi: 10.3390/antiox2040398, PMID 26784472.

18. Badnore AU, Sorde KI, Datir KA, Ananthanarayan L, Pratap AP, Pandit AB. Preparation of antibacterial peel off facial mask formulation incorporating biosynthesized silver nanoparticles. Appl Nanosci. 2019 Mar;9(2):279-87. doi: 10.1007/s13204-018-0934-2.

19. Parveen R, Baboota S, Ali J, Ahuja A, Vasudev SS, Ahmad S. Oil based nanocarrier for improved oral delivery of silymarin: in vitro and in vivo studies. Int J Pharm. 2011 Oct 31;413(1-2):245-53. doi: 10.1016/j.ijpharm.2011.04.041, PMID 21549187.

20. Chen Y, Wu Q, Zhang Z, Yuan L, Liu X, Zhou L. Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics. Molecules. 2012 May 14;17(5):5972-87. doi: 10.3390/molecules17055972, PMID 22609787.

21. Apriani EF, Miksusanti M, Fransiska N, Fitria E, Miksusanti AM. Formulation and optimisation peel off gel mask with polyvinyl alcohol and gelatin based using factorial design from banana peel flour (Musa paradisiaca L.) as antioxidant. Indones J Pharm. 2022;32(2):261-8. doi: 10.22146/ijp.3408.

22. Asthana N, Pal K, Aljabali AA, Tambuwala MM, De Souza FG, Pandey K. Polyvinyl alcohol (PVA) mixed green clay and aloe vera based polymeric membrane optimization: peel off mask formulation for skin care cosmeceuticals in green nanotechnology. J Mol Struct. 2021 Apr 5;1229:129592. doi: 10.1016/j.molstruc.2020.129592.

23. Pereira Filho JL, Mendes AG, Campos CD, Moreira IV, Monteiro CR, Soczek SH. A comprehensive review on the antibacterial, antifungal, antiviral and antiparasitic potential of silybin. Antibiotics (Basel). 2024;13(11):1091. doi: 10.3390/antibiotics13111091, PMID 39596784.

24. Donadio G, Mensitieri F, Santoro V, Parisi V, Bellone ML, De Tommasi N. Interactions with microbial proteins driving the antibacterial activity of flavonoids. Pharmaceutics. 2021 May;13(5):660. doi: 10.3390/pharmaceutics13050660, PMID 34062983.

25. Alshehri FS, Kotb E, Nawaz M, Al Jameel S, Amin KA. Preparation, characterization and antibacterial competence of silymarin and its nano-formulation. J Exp Nanosci. 2022;17(1):100-12. doi: 10.1080/17458080.2022.2041192.

26. Efenberger Szmechtyk M, Nowak A, Czyzowska A. Plant extracts rich in polyphenols: antibacterial agents and natural preservatives for meat and meat products. Crit Rev Food Sci Nutr. 2021;61(1):149-78. doi: 10.1080/ 10408398.2020.1722060, PMID 32043360.

27. Karanje AS, Kandale JB, Jadhav R, Patil M. Formulation development and evaluation of silymarin gel. Res J Pharm Technol. 2011;4(10):1633-6.

28. Ali MA, Kaid BM. Development and characterization of peel-off gel masks incorporating activated charcoal and salicylic acid for enhanced skin radiance and rejuvenation. Int J Pharm Sci. 2024;2(8):3024-34. doi: 10.5281/zenodo.13294604.

29. Ralli T, Tripathi T, Kalaiselvan V, Tiwari R, Aeri V, Kohli K. Silymarin as a phyto-pharmaceutical: isolation, simultaneous quantification of four biomarkers and in silico anti-inflammatory activity. Chin J Anal Chem. 2023 Mar;51(3):100174. doi: 10.1016/j.cjac.2022.100174.