(W1230-06-34) Optimizing Skincare with a Multifunctional Approach: Development of a Facial Booster Microemulsion Using Box-Behnken Design

Purpose: The aim of this work was to develop and characterize a multifunctional microemulsified facial booster (MFB) containing vitamin E, hyaluronic acid (HA), and phenylbenzimidazole sulfonic acid (PBSA) using a Box-Behnken experimental design (BBD).

Methods: Experimental

Design: A BBD with three levels (-1, 0, and 1) was employed to access the correlation between antioxidant activity (R1), occlusivity (R2) and sun protection factor (SPF) (R3) (dependent variables), based on the concentrations of active ingredients (independent variables): A - vitamin E (0.5 to 5%); B - HA (1 to 5%); and C - PBSA (0.5 to 7.5%). The experimental design was constructed using Design-Expert^® software and analyzed by ANOVA. MFB Production: The multifunctional facial booster (MFB) was prepared in two phases: an oily phase containing Kolliphor^® RH 40 (27.9 %), Span^® 80 (4.2 %), linseed oil (8%) and vitamin E; and an aqueous phase composed of HA, PBSA, and purified water (59.9 %). Both phases were heated separately to 40 °C under magnetic stirring to ensure complete solubilization of the components. After reaching the desired temperature, the aqueous phase was gradually added to the oily phase. The resulting mixture was then homogenized using an ultrasound probe at 40% amplitude for 4.5 min, a process that facilitates the formation of stable microemulsions by reducing droplet size and achieving a uniform distribution of components (1). Antioxidant Activity: Radical scavenging activity was measured against DPPH (1,1-diphenyl-2-picrylhydrazyl) (0.1 mM in ethanol) (2). MFB diluted in DMSO (10%, 1:20 _v/v) and DPPH solution were incubated in the dark at 25 ± 2 °C for 30 minutes. Absorbance was measured at 517 nm. Occlusivity: Occlusivity was evaluated using glass flasks containing 10 g purified water, covered with a microfiber filter onto which 100 mg formulation was applied. Flasks were kept at 38 ± 2 °C for 48 h, and water loss was calculated (3). SPF Evaluation: SPF was determined in vitro using et al.(4), by scanning the UVB range (290-320 nm) after prepared ethanol solutions (0.2 mg/mL) of each formulation (4). MFB Selection and Characterization: The optimal formulation was selected based on the highest antioxidant activity, occlusivity and SPF. Hydrodynamic droplet size and polydispersity index (PdI) were measured by Dynamic Light Scattering (DLS). pH value was determined by direct electrode insertion.

Results: The factorial design generated 20 experiments (Table 1). The mathematical models were selected based on statistical analysis, considering the highest values of R², adjusted R², predicted R², F-value, adequate precision, and the lack of significant lack of fit. These parameters are presented in Table 2. Regarding antioxidant activity, the data indicated that the linear models did not fit perfectly. However, the non-significant lack of fit value (p > 0.05) suggests that the linear model could still be used to explore the design space. The 3-D response surface plot (Figure 1a) shows the effect of the independent variables. Notably, increasing the PBSA concentration – the only significant factor (p < 0.05) – led to an increase in DPPH radical scavenging activity. For occlusivity, the quadratic model was not significant, indicating that the overall mean (18.18 ± 5.85%) may better predict the response than the fitted model. None of the terms were statistically significant (p > 0.05). Figure 1b presents the response surface plot for occlusivity. In the SPF evaluation, the linear model provides a good fit, with PBSA (C) concentration again being the only significant model term (p < 0.05). Figure 1c illustrates that increasing PBSA concentration enhanced the SPF value of the formulations. Based on the statistical analyses performed and the significance of the model terms, the optimized MFB formulation was prepared using Vitamin E (5 %), HA (5%), and PBSA (7.5%). This formulation exhibited a radical scavenging activity of 8.02 ± 1.20%, an occlusion factor of 27.65 ± 1.67% (indicating potential for skin hydration by reducing water loss), and an SPF value of 12.65 ± 1.33 (classified as SPF 12). The MFB presented a droplet size of 34.74 ± 0.14 nm, typical of microemulsions (droplet size < 100 nm) (5), and a PdI of 0.184 ± 0.024, indicating a homogeneous droplet size distribution (6). The pH was slightly neutral (7.14 ± 0.02), attributed to the PBSA solution (formulated with pH >7), making the product suitable for topical application (7).

Conclusion: The developed MFB demonstrated multifunctional potential, combining antioxidant properties, moisturizing capacity, and effective photoprotection, supporting its use as an innovative cosmetic skincare product.

References: (1) MIRANDA, Júlio Abreu. Desenvolvimento de nanoemulsão fotoprotetora à base de óleo de linhaça (Linum usitatissimum L.) e de filtros ultravioleta avobenzona e tris-biphenyl triazine (nano): Master Thesis -Universidade Federal do Rio Grande do Norte; 2022.
(2) SUN, Yan-Jun et al. Structurally diverse biflavonoids from Dysosma versipellis and their bioactivity. RSC Advances, v. 12, n. 54, p. 34962-34970, 2022.
(3) MILUTINOV, Jovana et al. Development and evaluation of quercetin topical emulgels: Physicochemical and rheological properties, stability and sun protective potential. Journal of Molecular Liquids, v. 417, p. 126568, 2025.
(4) MANSUR, Joäo de Souza et al. Determinaçäo do fator de proteçäo solar por espectrofotometria. Anais Brasileiros de Dermatologia, p. 121-4, 1986.
(5) CARBALLO, Diego et al. Development of food-grade microemulsions (F‒G μEms) for green extraction of bioactive compounds from Jalapeño waste (Capsicum annum var. Hot). Sustainable Chemistry and Pharmacy, v. 43, p. 101912, 2025.
(6) XU, Zhenbo et al. Co-surfactant free microemulsions: Preparation, characterization and stability evaluation for food application. Food Chemistry, v. 204, p. 194-200, 2016.
(7) IJAZ, Nida et al. Formulation and characterization of Aloe vera gel and tomato powder containing cream. Acta Ecologica Sinica. 2022.

Acknowledgements: This study was partially funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001, and by the Brazilian National Council for Scientific and Technological Development (CNPq) – Grant No. 443935/2024-6.


Table 1


Table 2


Figure 1