Multi-Active Cosmeceutical Formulations: Stability, Sensory Performance, and Skin Tolerability

Abstract

Cosmeceutical systems represent next-generation topical platforms designed to deliver bioactive molecules with therapeutic potential directly to the skin. This study evaluated four anti-wrinkle formulations (three creams and one emulgel) in terms of their stability, sensory characteristics, acceptability, and skin tolerance. The products incorporated a unique combination of active ingredients, including N-acetylcysteine, arginine HCl, Blainvillea camellia flower extract, tocopherol, and hyaluronic acid. For the cream formulations (EG01–EG03), different emulsifiers were employed, while EG04 was developed as an emulgel. Stability testing revealed that only three out of four formulations remained physically stable, with EG04 showing phase separation. Sensory analysis assessed parameters such as spreading, absorption, shininess, stickiness, greasiness, and smoothness, with results illustrated using a radar plot. EG01 and EG03 displayed similar sensory profiles, differing mainly in shininess and greasiness, while both exhibited high smoothness. In vivo testing was conducted on female human volunteers aged 50–65 years (Fitzpatrick skin types II–IV) to evaluate tolerance and acceptability. Only EG01 and EG03, formulated with methyl glucose sesquistearate and polyglyceryl-3-methylglucose distearate, respectively, demonstrated both superior sensory performance and 100% acceptability and tolerance in clinical assessment.

1. Introduction

The market segment of personalized cosmeceutical preparations has significantly expanded in recent years. Cosmeceutical products provide greater benefits than conventional cosmetics by incorporating bioactive ingredients with clinically proven therapeutic effects on the skin, such as antioxidants, peptides, and retinoids. Unlike traditional cosmetics, they target specific dermatological conditions, offering both esthetic improvement and functional skin health support. This concept is centered on developing products tailored to individual consumers’ unique needs and specific requirements [1,2,3]. Recognized as a niche segment, it is expected to gain increasing market traction as consumers seek products customized to their skin’s specific typology and structural needs. Over the past five years, numerous companies have emerged, successfully promoting this type of niche cosmetic preparation, tailor-made cosmetics, or bespoke skincare. These individualized cosmetics typically utilize predetermined cream bases into which various active ingredients or phytocomplexes are incorporated [3].

Integrating active substances, known for their therapeutic efficacy in specific conditions, into moisturizing and anti-aging cream bases results in personalized cosmeceutical preparations.

A topical formulation containing N-acetylcysteine (NAC) is considered innovative due to its multifunctional properties—serving as a potent antioxidant, anti-inflammatory, and precursor of glutathione—while also presenting significant formulation challenges related to its stability and bioavailability, thus offering advanced therapeutic potential in dermatological applications [4,5,6] (Figure 1).

Although both N-acetylcysteine (NAC) and glutathione are known for their potent antioxidant properties and involvement in redox homeostasis, NAC presents several distinct advantages that justify its selection over glutathione in topical cosmetic formulations. Firstly, NAC exhibits higher chemical stability, maintaining its integrity under typical formulation and storage conditions, whereas glutathione is easily oxidized to its inactive disulfide form (GSSG), particularly in aqueous environments, limiting its shelf life and formulation compatibility [7,8]. Secondly, due to its lower molecular weight (163.2 g/mol versus glutathione’s 307.3 g/mol), NAC demonstrates superior skin penetration, enabling it to pass more readily through the Stratum corneum and exert biological effects at the epidermal and dermal levels [9,10]. From a formulation standpoint, NAC is more versatile, showing good solubility in water, compatibility with various emulsifiers, and tolerance across a broad pH range, which allows its integration into different dosage forms without the need for complex encapsulation systems [11,12]. In contrast, glutathione often requires protective delivery technologies such as liposomes or nanocarriers to maintain stability and bioavailability. In terms of bioactivity, NAC not only acts as a direct scavenger of reactive oxygen species but also serves as a precursor in glutathione biosynthesis, thus amplifying the skin’s endogenous antioxidant defense systems. Additionally, it exhibits anti-inflammatory properties, modulating key signaling pathways and reducing the expression of pro-inflammatory cytokines, features that glutathione lacks [13,14]. Another practical considerations are the cost and availability. NAC is widely available in high purity and is more cost-effective for industrial-scale cosmetic production, whereas glutathione is typically more expensive and less accessible in pharmaceutical-grade quality [15,16]. Finally, NAC benefits from a more favorable regulatory profile, being broadly accepted for cosmetic use, while glutathione’s topical application is more variable and, in some jurisdictions, faces regulatory uncertainty or restrictions, particularly in formulations targeting skin lightening [17,18]. Taken together, these factors support the use of NAC as a more stable, effective, and economically viable alternative to glutathione in the development of antioxidant and anti-aging skincare formulations.

N-acetylcysteine (NAC) is a thiol-based compound with well-documented antioxidant and anti-inflammatory properties, making it highly relevant for dermatological and cosmetic applications. Its dual mechanism of action, acting both as a precursor to glutathione synthesis and as a direct scavenger of reactive oxygen species (ROS), plays a central role in protecting keratinocytes and fibroblasts from oxidative damage caused by UV radiation, pollution, and inflammation [19]. In addition, NAC modulates redox-sensitive inflammatory pathways such as NF-κB, leading to decreased levels of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), which supports its use in treating acne, dermatitis, and other inflammatory skin conditions [20,21]. Its mucolytic activity, derived from its capacity to cleave disulfide bonds, may also improve desquamation and hydration in the Stratum corneum, benefiting dry or scaling skin [22]. Emerging evidence highlights NAC’s ability to enhance epidermal barrier integrity, stimulate the expression of key proteins such as filaggrin and involucrin, and support moisture retention, especially in aging or compromised skin [23]. Furthermore, NAC contributes to wound healing by promoting cell proliferation, collagen synthesis, and redox balance, while also limiting scar formation [24,25,26]. From an anti-aging perspective, NAC has shown potential in preventing collagen degradation, reducing UV-induced DNA damage, and suppressing matrix metalloproteinases (MMPs), positioning it as a promising agent in photoaging prevention [14,27]. Topical application has also been shown to reduce transepidermal water loss (TEWL) and restore hydration in both healthy and atopic skin [28]. Due to its multifunctional bioactivity and growing support in both literature and industry reports, NAC is increasingly incorporated into premium cosmetic formulations, particularly those aimed at anti-aging, barrier repair, and oxidative stress protection [29]. Despite its somewhat unpleasant odor, NAC can be considered a highly potent active ingredient for advanced anti-aging creams and is actively seeking formulation strategies that maximize efficacy while remaining acceptable to consumers.

Recent studies indicate that antioxidants such as N-acetylcysteine can be highly effective when used as innovative antioxidant ingredients, mainly when administered topically and internally. Besides N-acetylcysteine, arginine, and Blainvillea acmella (L.) Philipson extracts were incorporated into cream bases tailored to specific skin typologies correlated with their benefits/local therapeutic effect [30,31,32].

Sensory evaluation, while traditionally more prominent in the cosmetic field, is increasingly recognized in pharmaceutical and cosmeceutical research as a valuable tool for optimizing topical formulations, as it enhances patient adherence, informs product acceptability, and provides critical insights into user experience—benefiting both researchers in developing patient-centered products and end-users through improved satisfaction and compliance. Ensuring a favorable sensory experience in cosmeceutical application is essential for promoting patient adherence, minimizing treatment discontinuation, and enhancing both perceived and potentially actual therapeutic efficacy, as positive sensory attributes can facilitate regular use, improve psychological response, and optimize active ingredient delivery. Sensory evaluation conducted by a trained panel represents a valuable tool in cosmeceutical development, providing reproducible and objective insights into texture, spreadability, absorption, and overall user perception. This approach enables early identification of formulation weaknesses, supports optimization based on scientifically relevant parameters, and enhances product differentiation in a competitive market. Moreover, by predicting consumer acceptability and improving user experience, such evaluations contribute to both product efficacy and long-term adherence.

The sensory evaluation follows different methodological approaches depending on whether the focal point is placed on the consumer or the product. Considering that the consumer is the last shackle for a topical product, the cosmeceutical should focus on the patient/consumer perception. Some evaluations/parameters widely used in the food industry have been adapted at an early stage for cosmetic product evaluation, especially those characteristic of semisolid products [5]. Such adjustments include product application areas on the skin (most commonly of the face and arms), the evaluation environment (in specially equipped booths or real-life conditions), and the evaluation steps (during and after the product application). Consumer opinions are assessed by employing preference tests (a questionnaire) with user panels in the product category (skincare, makeup, hair care, etc.). Information that discriminates or characterizes the sensory properties of the products is obtained with trained and validated panels of experts for the method used [33,34]. Subjects involved in sensory evaluation must undergo appropriate training to accurately identify and distinguish even the most subtle sensory effects. This necessitates the inclusion of participants who are knowledgeable, qualified, or even expert evaluators. Traditionally, quantitative descriptive profiling methods are used to characterize the sensory perceptions of cosmetic products. These methods qualify and quantify cosmetics’ visual and textural properties with adapted lexicons [3,21].

Quantitative descriptive profiling methods are adopted to evaluate the sensory perceptions of cosmetic products. These methods enabled the qualification and quantification of the visual and textural properties of cosmetics using specialized lexicons. The resulting sensory profile often indicates evidence of compliance with specifications during product development and the product’s lifespan [35,36,37]. Sensory evaluation methods are now widely implemented in cosmetic companies, adhering to the NF ISO 11035 standard [38,39,40] the following properties being evaluated: appearance (including visual properties before any manipulation), handling (corresponding to the properties perceived when the product is manipulated), application (including the properties, felt when the product is applied to the skin), after-feel (residual appearance), which is the feeling after penetration of the product, and removal (the feeling after the product is rinsed off the skin) (Figure 2).

The first objective of this study was to develop stable semisolid formulations in terms of creams and emulgels (under the action of shear force) that incorporate N-acetylcysteine as an ingredient in a complex semisolid matrix, and the sensorial analysis was assessed in the case of the stable formulations. From a pharmaceutical perspective, emulsion-based creams, due to the inclusion of emulsifiers, act as absorption enhancers, facilitating deeper dermal penetration of active ingredients compared to gels or emulgels. While gels mainly allow superficial cutaneous absorption through pilosebaceous units, emulsified systems have the potential to deliver bioactive compounds into deeper skin layers more efficiently, especially when true emulsifiers are present. Gels and emulgels are typically formulated using matrix-forming polymers, which are predominantly synthetic or semi-synthetic, and only rarely of natural origin. These polymers are not absorbed into the skin; they remain on the surface and generally provide no direct therapeutic or cosmetic benefit to the skin itself. Despite the popularity of gels and emulgels among consumers—owing to their rapid absorption and favorable sensory characteristics—their effectiveness in delivering active ingredients can be limited. Given the superior therapeutic profile of emulsified systems, this study aimed to develop and evaluate three emulsion-type cream formulations and only one emulgel, seeking an optimal balance between consumer acceptance and dermal bioavailability of the active compounds. Few semisolid preparations include N-acetylcysteine on their ingredient list [4,30], even though its antioxidant capacity has been proven through the ability of N-acetylcysteine to act as a reduced glutathione precursor (source of cysteine for glutathione biosynthesis), another mechanism mentioned being that N-Acetylcysteine scavenges directly through its thiol groups [4,6,31]. In order to highlight the most suitable formulas, a series of studies were carried out, such as the evaluation of stability under the action of shear force, sensory analysis by evaluating six sensory attributes (Spreading, Absorbency, Shininess, Stickiness, Greasiness, and Softness). The formulation under investigation combines these potent ingredients with additional bioactive components known for their dermatological benefits, including Blainvillea acmella flower extract, tocopherol, hyaluronic acid, aloe vera extract, and Olea europaea (olive) oil. N-acetylcysteine exhibits remarkable antioxidant activity even at low concentrations (0.1–5%). However, its application in topical products is constrained by its characteristic unpleasant odor, which limits its inclusion to concentrations no higher than 5%.

The second objective aims to verify the acceptability and tolerance of the proposed cosmetic product when applied to the skin, the tests being carried out on a group of healthy human subjects after application under normal conditions of use for 28 consecutive days. Tolerance involves the product’s compatibility with the skin, ensuring it does not irritate or produce any allergic reactions or other side effects. High tolerance is essential for long-term use and overall consumer satisfaction. Screening of acceptability and tolerability on a panel of human subjects selected for personalized cosmetic product use will be of particular value.

Despite the well-documented pharmacological applications of N-acetylcysteine (NAC), its use in topical cosmetics—particularly within anti-aging formulations—remains relatively limited. Nevertheless, interest in this compound has grown significantly in recent years, leading to its inclusion in complex dermocosmetic products, especially within premium or customized skincare lines. A notable example is the NAC Y²™ used in the 111 SKIN-skincare products, which incorporates a patented complex of NAC, vitamin C, and escin, formulated in serums and anti-aging creams aimed at reducing wrinkles, improving skin firmness, and protecting against oxidative stress. In addition, several reputable brands have integrated NAC into targeted formulations. For instance, ZO^® Skin Health uses NAC in its Sulfur Masque, where it functions as an antioxidant, anti-inflammatory, and sebum-regulating agent, designed for oily or acne-prone skin. NEOVA^® has developed DNA Damage Control Silc Sheer 2.0, where NAC supports photoprotection by enhancing DNA repair mechanisms and scavenging reactive oxygen species. The brand Jan Marini^®, through its Age Intervention Duality MD product, utilizes NAC to reinforce skin barrier function and reduce adult acne, while simultaneously addressing visible signs of aging. In clinical dermatology, compounded formulations containing NAC are frequently prescribed for conditions such as acne, melasma, and wound healing. Historically, NAC has also been included in formulations from Murad^®, particularly in the Essential-C Toner, as part of an antioxidant defense system against environmental pollutants (although this formula has since been reformulated). Furthermore, in K-beauty clinics, NAC-based mesotherapy serums are employed post-procedure (e.g., laser, microneedling) to stimulate collagen synthesis, reduce erythema, and accelerate skin recovery. These examples underscore NAC’s multifunctional role in dermatocosmetic science as an antioxidant, glutathione precursor, anti-inflammatory agent, and skin-repair booster. Accordingly, topical formulations containing NAC represent a promising direction in the development of anti-aging, anti-pollution, and skin-barrier-supporting skincare products.

Notably, none of the existing commercial products incorporates over 95% active ingredients or combine N-acetylcysteine with the specific set of bioactive compounds proposed in the experimental formulations, coded EG01, EG02, EG03, and EG04.

2. Materials and Methods

Two types of semisolid formulations were considered: creams (EG01–EG03) and emulgel (EG04). In the case of the cream formulations, the emulsifier group was systematically varied as follows: methyl glucose sesquistearate and stearic acid for EG01, Ceteareth-20 and cetyl alcohol for EG02, and polyglyceryl-3-methyl glucose distearate and stearic acid for EG03, while in the case of the last formulation (EG04), another type of pharmaceutical formulation was considered (emulgel) using Carbopol^® 971-PNF as a gel-forming agent.

2.1. Formulation of Cosmeceutical Products (EG01, EG02, EG03, EG04)

To obtain the semisolid preparations, creams (EG01–EG03) or emulgel (EG04), the ingredients used, the supplier, and the INCI Key were highlighted in

Table 1. The composition of the formulations proposed for evaluation in this study.

Ingredient	Supplier (Location)	EG01 (w/w)	EG02 (w/w)	EG03 (w/w)	EG04 (w/w)
Arginine HCl	Fagron (Trikala-Larissa, Greece)	1.00	1.00	1.00	1.00
N-acetylcysteine	Fagron (Trikala-Larissa, Greece)	1.00	1.00	1.00	1.00
Blainvillea acmella flower extract	Select Botanical (Barcelona, Spain)	0.20	0.20	0.20	0.20
Tocopherol	Merck (Darmstadt, Germany)	0.20	0.20	0.20	0.20
Hyaluronic acid	Fagron (Trikala-Larissa, Greece)	1.00	1.00	1.00	1.00
Aloe vera extract	Fagron (Trikala-Larissa, Greece)	10.00	10.00	10.00	10.00
Olea europaea oil	Fagron (Trikala-Larissa, Greece)	25.00	25.00	25.00	25.00
Euxyl™ PE 9010	Dow Chemical (Midland, MI, USA)	0.50	0.50	0.50	0.50
Methyl Glucose Sesquistearate	Lehvoss (Origgio, VA, Italy)	1.00	–	–	–
Ceteareth-20	Lehvoss (Origgio, VA, Italy)	–	1.00	–	–
Polyglyceryl-3 Methylglucose Distearate	Lehvoss (Origgio, VA, Italy)	–	–	1.00	–
Carbopol® 971 PNF	Lehvoss (Origgio, VA, Italy)	–	–	–	1.00
Stearic acid	Medchim TM (Bucharest, Romania)	3.00	–	3.00	–
Cetyl alcohol	Medchim TM (Bucharest, Romania)	–	3.00	–	–
Glycerol	Medchim TM (Bucharest, Romania)	–	–	–	3.00
Triethanolamine	Medchim TM (Bucharest, Romania)	–	0.25	–	–
Purified water q.s. * to 100	–	ad 100	ad 100	ad 100	ad 100

* q.s. (quantum satis) indicates that purified water was added to complete the formulation to 100% (w/w).

.

2.2. Preparation of Cosmeceutical Products

2.2.1. Emulgel Preparation

The preparation of the emulgel follows a standardized methodology. The preparation of the gel base involves dissolving a predetermined amount of polymer in 80% of the water with triethanolamine. The homogenization for emulgel was carried out with an automatic device, using a predetermined number of rotations per minute (Gako Unguator EM, Scheßlitz, Germany). Hyaluronic acid hydration was achieved in 30 min, together with 20% (w/w) water provided in the formula and aloe vera extract. Hydrated hyaluronic acid, along with Olea europaea oil, arginine hydrochloride, N-acetylcysteine, Blainvillea acmella flower extract, and tocopherol, were introduced into the pre-formulated gel base under stirring conditions at a rotational speed of 300 RPM. Subsequently, the stirring speed was increased to 800 RPM and maintained for 9 min. Following this, the speed is reduced to 300 RPM to ensure thorough mixing, continuing until a uniform gel is achieved [41]. At the final stage of the process, the preservative Euxyl™ PE 9010 is added to the mixture.

2.2.2. Emulsion Creams Preparation

Formulation of O/W or W/O type of emulsion creams involves heating the lipophilic phase until it becomes fluid and simultaneously heating the hydrophilic phase to the same temperature as the lipophilic phase. The two phases are then combined, mixed, and homogenized, with continuous mixing maintained until the mixture cools. The homogenization for creams was carried out with an automatic device for 9 min with a predetermined number of RPM (Gako Unguator EM, Scheßlitz, Germany). Hyaluronic acid hydration was achieved as described in the previous subchapter. Hydrated hyaluronic acid, arginine hydrochloride, N-acetylcysteine, Blainvillea acmella flower extract, and tocopherol are introduced into the O/W or W/O emulsion creams under stirring conditions at a rotational speed of 300 RPM. Subsequently, the stirring speed is increased to 800 RPM and maintained for 3 min. Following this, the speed is reduced to 300 RPM to ensure thorough mixing, continuing until a uniform gel is achieved. At the final stage of the process, the preservative Euxyl™ PE 9010 is added to the mixture.

2.3. Stability of Cosmeceutical Products Under the Action of Shear Forces

The four cosmeceutical formulations were subjected to centrifugation for 10 min at 4000 rpm, immediately after preparation (T0), 7 days (T1), 14 days (T2), 30 days (T3), 60 days (T4) and 90 days (T5) after preparation, using an MPW-260 R type centrifuge. The test was repeated three times on samples of 2 mL each, and the results were expressed as average ± standard deviation (SD). The formulations were stored in opaque high-density polyethylene (HDPE) containers with screw caps and opercula at room temperature (15–25 °C, protected from light, immediately after preparation and subsequently until analysis at predeterminated intervals (7, 14, 30, 60 and 90 days).

Formulas that were not stable 90 days after the preparation step were excluded from the study.

2.4. Organoleptic Characteristics and pH Formulations Evaluation

The formulations were evaluated for their organoleptic properties, including appearance, color, texture, and odor, both immediately after preparation and at 90 days post-preparation, as part of the observation period. These parameters are essential indicators of consumer acceptability and serve as critical criteria in initial quality control. The evaluation of appearance, color, and odor was performed following relevant regulatory guidelines and the established literature in the field.

pH determination was carried out following a dilution step, in which the samples were mixed with distilled water in a 1:5 (w/v) ratio. The pH of the diluted samples was measured using an Orion 3 Star pH meter equipped with a glass electrode (Thermo Scientific, Waltham, MA, USA), under controlled laboratory conditions.

Organoleptic evaluations and pH measurements were performed on the formulations EG01, EG02, and EG03.

2.5. Sensory Analysis

To obtain the sensory profiles, the following products were used: the reference products used to help the assessors rate the products on the 0–10 intensity scales for each of the six chosen attributes (spreadability, shininess, stickiness, greasiness, softness, and absorbency), and the three formulated products coded: EG01, EG02, EG03 (Figure 3). For each attribute, four reference products are displayed and represented at 0.5, 3.5, 6.5, and 9.5 scale values (

Table 2. The intensity scale for the evaluated parameters.

Spreading	Spreading Difficulty ET0.5	ET3.5	ET6.5	Very Easy Spreading ET9.5
Absorbency	Very absorbent (5–10 rotations)	35 rotations	65 rotations	Non-absorbent >95 rotations
Shininess	Mast (BR0.5)	BR3.5	BR6.5	Brilliant BR9.5
Greasiness	Not greasy/dry Bare skin GR0.5	GR3.5	GR6.5	Very greasy GR9.5
Stickiness	Not sticky Bare skin CO0.5	CO3.5	CO6.5	Very sticky CO9.5
Softness	Not smooth DX0.5	DX3.5	DX6.5	Very smooth (dry and slippery) DX9.5

). The assessor does not receive any information about the reference product, the type of product, or its composition, only the fact that the product is the reference for a specific sensorial attribute and the specific numerical evaluation/mark.

This study involved 12 female Caucasian-trained assessors, with ages ranging from 21 to 26 years old, selected and trained according to the guidelines in ISO 8586-1, ISO 13299 [39,40,42]: standardized booths, uniform lighting, and odor neutrality. Testing took place at the sensory facilities of URCOM laboratory (Le Havre Normandy University, France) at 20.5 ± 0.4 °C and 43.0 ± 1.4% relative humidity. All formulated products were submitted to a microbiological safety assessment to ensure that the products could be safely applied to the assessor’s skin. Both in vivo studies presented here have been carried out following The Code of Ethics of the World Medical Association (Declaration of Helsinki) and have been approved by the Ethical Committee of Le Havre Normandy University. All subjects participated only after receiving detailed oral and written information and signing an informed consent agreement.

The assessors were trained in two training sessions followed by two analysis sessions, in which samples were evaluated once [40]. Samples (50 µL) were labeled with different three-digit random numbers for each session and were randomly presented in 5 mL opaque vials. Each assessor was allowed to test the product several times if needed. The analysis was conducted on the internal side of the non-dominant forearm. Before starting, each assessor cleaned the hands and forearms with the hydroalcoholic gel provided.

The attribute definitions were defined as follows:

• Spreading: good spreading capacity to move/spread the product on the skin, performed by circular movements.
• Absorbency: the number of rotations needed to ensure the product penetration into the skin. It occurs until the subject feels a resistance or a rubbing between the finger and the skin during the application.
• Shininess: amount of light reflected by the skin immediately after application of the product, after absorption.
• Stickiness: force required to lift the index finger from the skin.
• Greasiness: amount of grease (rich feeling, butter) perceived between thumb and index finger taken by lightly pinching the skin after penetration.
• Softness: easy to slide the fingers over the skin 1 min after penetration, a dry, slippery feel is characteristic of softness.

The protocol was developed to reproduce and mimic the spreading speed of skin care products in normal conditions. Thus, the assessors were asked to draw a circle of 6 cm in diameter on their forearm and pick-up 50 μL of product, using a positive displacement pipette (Gilson MicroMan, Middleton, WI, USA), and applied by following the beat of a metronome (90 rpm), by not exceeding the circle area. Spreading and absorbency are measured during the rub-out phase, while shininess is measured after application. Greasiness and stickiness are measured 1 min after application and softness 2 min after application of the product. All attributes were evaluated in duplicate by all assessors and the data obtained was double-checked.

2.6. Screening Test for Checking the Skin Acceptability and Tolerance of Cosmeceutical Products

2.6.1. Skin Reactions Evaluation/Recording

The test subjects were requested to note the everyday reactions observed, and the sensation of discomfort felt in the daily log they were given at the beginning of the study.

A skin examination was performed at the investigating center:

• Visually, by the same investigator or technician, supervised by the investigator, under a standard “daylight” source,
• Before the 1st application of the investigational product (D1/T0) then after 28 consecutive days of product use (D29),

Concurrently with the clinical examinations performed after the use of the investigational product, the test subjects were questioned about the possible sensations of discomfort they felt. Digital photographs of the skin had to be systematically taken when justified (adverse effects), with the test subject being non-recognizable.

2.6.2. Expression and Interpretation of the Results

The test subjects had to note any reaction or sensation of discomfort in the daily log, using their own words to express what they experienced (

Table 3. Synopsis for comparative screening test.

Test subjects	Number of test subjects: 5 valid cases Specific inclusion criteria: test subjects
	Aged from 50 to 65 Female With a phototype (Fitzpatrick): II–IV Regular users of face care cosmetic products Specific non-inclusion criteria: test subjects With a family or personal history of atopy
Methodology	Application of the investigational product EG01:
	Application at home by the test subjects under normal conditions of use, for 28 consecutive days Application site: one hemi-face, including the eye contour area. Duration: 28 ± 2 consecutive days Frequency of use: twice a day, in the morning and evening Investigational product directions for use: application of the product by gentle digital massage until complete penetration Application of the investigational product EG02: Application at home by the test subjects under normal conditions of use, for 28 consecutive days Application site: other hemi-face, including eye contour area. Duration: 28 ± 2 consecutive days Frequency of use: twice a day, in the morning and evening Investigational product directions for use: application of the product by gentle digital massage, until complete penetration
Evaluation of skin acceptability and tolerance	Checking of the skin acceptability (local tolerance) based on:
	a skin examination of both hemi-faces by the investigator or by the technician: before product application (D1/T0) after 28 ± 2 consecutive days of product use (D29) The analysis of the sensations of discomfort reported directly by the test subjects to the investigator or the technician, during the study or in the daily logs Descriptive analysis—Percentage of reactive test subjects

).

In case of reactivity, the investigator or technician supervised by the investigator had to note [41,42,43]:

• The visible clinical signs: Erythema, Edema, Dryness/Desquamation.
• The sensations of discomfort declared by the test subjects: Heating, Burning, Stinging, Itching, Pulling, Redness, Watering, or foreign body sensation (in case of accidental contact with the eye mucous membrane) (

  Table 4. The score used for visible clinical signs and the sensations of discomfort.

  Erythema	Edema	Skin Dryness	Papules	Pustules	Sensations of Discomfort
  Score 0: no erythema Score 1: very slight erythema Score 2: slight erythema Score 3: moderate erythema Score 4: severe erythema	Score 0: no edema Score 1: more or less important edema	Score 0: no dryness Score 1: slight dryness Score 2: moderate dryness Score 3: important dryness	Score 0: no papule Score 1: presence of few papule(s) Score 2: the presence of numerous papules	Score 0: no pustule Score 1: presence of few pustule(s) Score 2: presence of numerous pustules	Score 0: no sensation of discomfort Score 1: very slight sensation of discomfort Score 2: slight sensation of discomfort Score 3: moderate sensation of discomfort Score 4: severe sensation of discomfort

  ).

The investigator or the technician specified the clinical signs and the sensations of discomfort, the location, duration, period of occurrence after application of the investigational product, frequency, intensity, evolution, and medical treatment undertaken, then calculated the percentage of reactive test subjects [41,43,44,45,46,47]. The intensity of the main visible clinical signs and the sensations of discomfort were assessed according to ordinal scales (as defined in the procedures of the investigating center).

2.6.3. Statistical Processing of Sensory Data

Statistical double-checked analyses of collected data were performed on the XLSTAT^® software package, version 2018.7 (Addinsoft, Paris, France). Single-, two- or three-way analyses of variance (ANOVA) were applied to evaluate the assessor’s performances and product discrimination. Results were reported as average ± SD. Regarding the Tukey test, if the group means are close to each other, they receive the same letter; if the group averages are different, they receive a different letter. If an average result is coded with both letters (ab), that implies that the result is not different from a statistical point of view from either group a or group b.

3. Results and Discussion

3.1. Preparation of Cosmeceutical Creams

All proposed formulations possess an esthetically refined appearance, characterized by the creams’ white to slightly yellowish color and the emulgel’s translucent golden color. The proposed formulas had a homogeneous appearance and a characteristic smell of the components, the intensity of the color being influenced by the emulsifier used, or in the case of the emulgel, by the mold-forming polymer (Figure 4).

3.2. Stability of the Cosmeceutical Products Under the Action of Shear Forces and the Selection of the Formulas According to Their Stability

After the centrifugation test, the formulated products were included in one of the following categories: homogeneous (h—where no signs of separation occur), slight signs of phase separation—ss, and phase separation—ps (Figure 5).

All four formulas were homogenous after the centrifugation test immediately after preparation, seven days after preparation, 14 days after preparation, 30 days after preparation, 60 days after preparation and 90 days after preparation (

Table 5. Stability test by centrifugation.

Formula	T0	T1	T3	T4	T5
EG01	h	h	h	h	h
EG02	h	h	h	h	h
EG03	h	h	h	h	h
EG04	h	h	h	ss	ps

Appearance following the centrifugation stability test: T0-immediately after preparation, T1–7 days after preparation, T2–14 days after preparation, T3–30 days after preparation, T4–60 days after preparation, T5–90 days after preparation, h—where no signs of separation occur), slight signs of phase separation—ss, and phase separation—ps.

). 60 days after preparation (T1) following the centrifugation test, the EG04 formulation showed slight signs of phase separation whilst EG01, EG02, and EG03 were homogeneous. 90 days after preparation (T5) EG04 showed signs of phase separation, whereas EG01, EG02, and EG03 were still homogenous.

After centrifugation for 10 min at 4000 revolutions per minute (rpm), the formula must be stable even after 90 days of preparation; as a result, formula EG04 will be excluded from future studies/analysis.

Although the EG04 formulation demonstrated physical stability in the centrifugation test immediately after preparation, clear signs of phase separation were observed 60- and 90 days post-preparation. These findings strongly suggest that the current emulgel formulation is not suitable for long-term stability and, therefore, should be excluded from further analysis. In future studies, it is intended to explore an alternative emulgel formulation, potentially incorporating a different type of polymer with enhanced structuring capacity to improve system stability.

All three emulsion-based formulations (EG01, EG02, and EG03) exhibited excellent results in the centrifugation test, from the time of preparation through 90 days post-preparation. The absence of any signs of phase separation throughout this period indicates a high level of physical stability. Consequently, only these three formulations will be considered for further investigation, and the most promising candidate will be subjected to comprehensive stability testing, including evaluation in its final packaging. The key differentiating factor among these three formulations lies in the type of emulsifier used. EG01 employs methyl glucose sesquistearate, a true emulsifier capable of forming water-in-oil emulsion systems. EG02 contains Ceteareth-based emulsifiers, which are known to form light and stable oil-in-water emulsions. EG03 utilizes polyglyceryl-3-methylglucose distearate, a next-generation emulsifier designed to create stable oil-in-water systems with improved sensory properties. Aside from the emulsifier type, all other active ingredients were used in identical proportions across the three formulations. Notably, the active compounds represent more than 95% of the total formulation, a rare feature in cosmetic emulsions. Achieving such a high active content while maintaining excellent emulsion stability highlights the robustness and effectiveness of the chosen formulation strategies.

The stability of a cosmetic product is extremely important, which is why the elimination of the unstable formulas was considered [47,48].

Stability testing can be conducted at various levels. In the cosmetic and pharmaceutical industries, preliminary assessments, such as the centrifugation test, are initially employed. Subsequently, stability can be evaluated using additional methods. A common approach involves maintaining the product at extremely low or high temperatures for a specified duration. For instance, other studies assess the stability of topical products by storing them in the dark at 30 °C for three months to evaluate their chemical and physical stability [49,50,51,52].

The stability of an emulsion system plays a critical role in sensory evaluation. The structural composition of the emulsion, along with the size distribution of water or oil droplets, can significantly impact the texture, esthetic appeal, and long-term stability of the emulsion [53,54,55]. These characteristics are largely influenced by the selection and interaction of emulsifiers and co-emulsifiers. The preparation method, along with the choice of emulsifiers and co-emulsifiers, significantly affects the final sensory characteristics of the emulsion. The distribution and arrangement of droplets in the internal phase of the emulsion are primarily governed by emulsifiers such as methyl glucose sesquistearate, Ceteareth-20, and polyglyceryl-3-methylglucose distearate. Additionally, viscosity-enhancing agents play a crucial role in modulating the consistency and sensory perception during the final application of the cosmetic product [56,57,58].

Following the dynamic stability test, the EG04 formula showed slight signs of separation 60 days after preparation, whilst after 90 days after preparation, the EG04 formula showed visible signs of phase separation. Even if this EG04 formula presented a pleasant appearance after preparation, it did not pass the stability test at 60 and 90 days; as a result, it was considered that this formula could not be marketed, requiring formulation improvement.

All three formulations, EG01, EG02, and EG03, demonstrated stability by remaining homogeneous when subjected to centrifugation at 4000 rpm for 10 min, even after 60 and 90 days following their preparation.

The formulations EG01, EG02, and EG03 have been identified as stable (considering the stability test assessed) and have consequently been chosen for further assessment through sensory analysis and tolerance/acceptability tests conducted on human subjects. The stability and sensory properties of the semisolid preparations are of high importance for both sides (the cosmetic industry and the customer) [59,60,61]. The cosmetic market has exponentially developed, and the quality stipulations for these types of products are numerous [53,54,55,56].

3.3. Organoleptic Characteristics and pH of the Formulations

All tested formulations exhibited a homogeneous and stable appearance, with no visible signs of phase separation, discoloration, or odor alteration at the time of preparation or after 90 days of storage. Organoleptic evaluations and pH measurements were performed only on the formulations that demonstrated excellent physical stability following centrifugation testing, specifically formulations EG01, EG02, and EG03.

The pH values and organoleptic characteristics (appearance and color) of the three selected formulations (EG01, EG02, and EG03) were monitored immediately after preparation and again after 90 days of storage under controlled laboratory conditions. The results are summarized in

Table 6. The organoleptic properties of the developed creams.

Formula	Day 0			Day 90 After Preparation
	pH	Appearance	Color	pH	Appearance	Color
EG01	5.68		Milky-white	5.65		Milky-white
EG02	5.85		Milky-white	5.90		Milky-white
EG03	5.87		Milky-white	5.83		Milky-white

.

All formulations maintained pH values within the skin-compatible range (4.5–6.5) over the 90 days, indicating good chemical stability (Table 6). Minor variations in pH (≤0.05 units) were observed, but these changes are not considered significant in terms of product safety or performance.

From an industrial and consumer-oriented perspective, the physical and visual stability of a cosmetic formulation over time is a critical determinant of market success and user satisfaction. The consistent milky-white appearance, absence of phase separation, and preservation of a pleasant sensory profile after 90 days of storage reflect a high degree of formulation robustness. These characteristics are essential not only for product efficacy and safety but also for esthetic appeal, which strongly influences the consumer’s perception of quality and their likelihood of repeat purchase.

Moreover, visual uniformity and minimal color shifts contribute to brand credibility and regulatory acceptance, especially in markets where stability claims are tied to product claims and labeling requirements. The observed short-term stability thus offers a promising foundation for scale-up, commercial launch, and regulatory approval, provided that further long-term and accelerated stability tests confirm the formulation’s performance across varied environmental conditions.

3.4. Sensory Analysis of the Anti-Wrinkle Cosmeceutical and Impact of the Composition

The first step involved assessing the performance of the assessors, followed by the evaluation of the product. Repeatability, discrimination, and consensus among assessors allow us to validate the performance metrics and the reliability of the sensory panel. The three analyzed products were found as non-significantly different by the assessors on the spreading behavior and the greasiness (p-value > 0.05) (

Table 7. The statistical analysis regarding the Summary of Product (Tukey test).

Products	Spreading	Absorbency	Shininess	Stickiness	Greasiness	Softness
EG01	5.10 ± 1.10 a	21.75 ± 7.65 b	3.46 ± 1.67 a	1.48 ± 1.08 b	2.31 ± 1.05 a	5.44 ± 1.24 a
EG02	4.65 ± 1.26 a	18.50 ± 5.63 b	5.17 ± 1.56 ab	2.79 ± 1.37 a	2.65 ± 1.40 a	4.21 ± 1.89 b
EG03	5.02 ± 1.02 a	29.13 ± 13.96 a	4.35 ± 1.58 b	1.58 ± 1.19 b	2.85 ± 1.10 a	5.33 ± 1.68 a

). The superscript letters (e.g., a, b) indicate statistically significant differences between group means, as determined by a post hoc multiple comparison test (such as Tukey’s HSD) following one-way ANOVA analysis. Means sharing the same letter are not significantly different from each other (p > 0.05), whereas those labeled with different letters differ significantly (p < 0.05). A mean annotated with a combination of letters (e.g., ab) denotes an intermediate value that does not differ significantly from groups labeled either a or b.

A critical consideration in this study is that all formulations were standardized to contain the same concentration of active ingredients. This design choice ensures that any variations in sensory perception can be directly attributed to differences in the type and amount of emulsifiers used, rather than to variations in the functional components of the formulations. By maintaining consistency in the active ingredient content, the role of the emulsifier system in shaping the sensorial profile of the creams can be accurately assessed.

The sensory analysis therefore focuses on key attributes influenced by the emulsifier composition, including how the product spreads on the skin, how rapidly and effectively it is absorbed, the degree of surface shininess it imparts, the level of stickiness and greasiness left after application, and the overall smoothness or softness perceived by the user. These characteristics are essential for evaluating the cosmetic elegance and user acceptability of topical formulations, as they directly impact the perceived quality and comfort of use.

Spreading behavior refers to how easily and evenly a product distributes over the skin. It is critical for user satisfaction because it affects the ease of application and the amount of product needed [62,63]. Products that spread well create a smooth, uniform layer, reducing the likelihood of product waste and ensuring even coverage [63]. A radar profile (Figure 6a–c) has been traced for a better comparison of the three products according to the different attributes. For a better analysis of the results, the absorbance attribute was transformed into a radius value by dividing the value obtained by 10, to include this parameter in the proposed scale (0–10). It can be noticed that in terms of spread, the three products present an easy to moderate spreading (values between 4.6 and 5.1) (Figure 6a–c), which is an essential property that greatly influences a product’s overall user experience. Upon comparing the results of the three formulations with data reported in the literature, it is observed that their spreading rates exhibit superior performance [53,54]. Tafuro et al., also documented moderate mean spreading values of 5.21 for similar formulations [64,65]. Despite the absence of silicones or silicone derivatives in the present study, it has been revealed that the formulations exhibit similar or better spreadability compared to those containing these ingredients. The following ingredients like Dimethicone or polysilicon 11 were excluded due to numerous reported cases of allergic reactions associated with these compounds since 1984 [62].

Greasiness refers to the oily or sticky residue a product may leave on the skin after application. Consumers generally prefer non-greasy products for comfort and to avoid feeling like the skin is coated. Greasiness affects the product’s perceived heaviness and its appeal for daily use. Although different emulsifiers were used in each formula—methyl glucose sesquistearate and stearic acid in EG01, Ceteareth-20 and cetyl alcohol in EG02, and polyglyceryl-3-methyl glucose distearate and stearic acid in EG03—no significant statistical differences were observed in terms of spreading behavior and greasiness after feel. The three products have low greasiness properties. This suggests that, despite the differences in emulsifier composition, their effect on these specific sensory attributes was minimal. The emulsifiers selected may share similar mechanisms in stabilizing the formulations, leading to comparable sensory outcomes across all products. Additionally, their influence on parameters like the formation of the oil-water interface and the consistency of the emulsion likely contributed to the uniformity in perceived tactile properties. Methyl glucose sesquistearate is a lipophilic emulsifier with an HLB (Hydrophilic-Lipophilic Balance) value typically in the range of 4 to 6. This relatively low HLB value indicates that it is more lipophilic (oil-attracting) than hydrophilic (water-attracting), making it suitable for stabilizing water-in-oil (W/O) emulsions. Its lipophilic nature helps in forming stable emulsions by reducing interfacial tension between the oil and water phases, while also influencing the droplet distribution and size in the internal phase of the emulsion. Ceteareth-20 is a hydrophilic emulsifier with an HLB (Hydrophilic-Lipophilic Balance) value typically ranging from 15 to 18. This relatively high HLB value indicates that Ceteareth-20 is more hydrophilic (water-attracting) than lipophilic (oil-attracting), making it well-suited for stabilizing oil-in-water (O/W) emulsions. Its hydrophilic properties enable it to effectively reduce the interfacial tension between the oil and water phases, promoting the formation of stable emulsions with a fine droplet distribution and improved texture, stability, and sensory characteristics in the final product [63,64,65,66,67]. As an emulsifier, polyglyceryl-3-methylglucose distearate helps reduce the interfacial tension between the oil and water phases, ensuring the formation of stable emulsions with fine droplet distributions. Its mild hydrophilic nature enhances the emulsion’s ability to maintain stability over time, contributing to smooth texture, consistency, and sensory appeal, particularly in cosmetic and skincare products.

Contrarily, the choice of emulsifiers in each formula—methyl glucose sesquistearate and stearic acid in EG01, Ceteareth-20 and cetyl alcohol in EG02, and polyglyceryl-3-methyl glucose distearate and stearic acid in EG03—resulted in noticeable differences in sensory properties such as absorbency, shininess, stickiness and softness (p-value < 0.05) (Table 6).

Absorbency or penetration is a critical sensory attribute in cosmetic formulations, especially in skin care products, as it influences the user’s perception of how quickly and effectively a product is absorbed into the skin. It is closely linked to consumer satisfaction because it can affect other sensory properties like greasiness, stickiness, and the overall feel of the product post-application. However, evaluating absorbency can be challenging due to its subjective nature and the variability between individual perceptions. In this case, the EG01 and EG02 were found to absorb faster than EG03, which requires about 10 more rotations to be performed on the skin before the product is estimated absorbed. Even so, the results are close to each other, all the values are in the first or at the beginning of the second quartile, which means that all of them exhibited good absorbency properties. These variations can be attributed to the different molecular structures, hydrophilic-lipophilic balance (HLB) values, and emulsification capacities of the emulsifiers. For instance, emulsifiers with a higher HLB, like Ceteareth-20, tend to create lighter emulsions that absorb faster, reducing stickiness and enhancing absorbency. On the other hand, emulsifiers with lower HLB values, like polyglyceryl-3-methyl glucose distearate, may form thicker, more occlusive emulsions, resulting in a shinier appearance and potentially more prolonged skin hydration but increased stickiness. Additionally, the fatty alcohols and acids used (e.g., cetyl alcohol and stearic acid) contribute to the tactile feel, influencing softness and the overall emollient effect on the skin. Therefore, the emulsifiers in each formula play a critical role in modulating the balance between sensory attributes like shine, absorbency, and texture.

In cosmetics, shininess represents another key sensory attribute that significantly influences product perception, depending on the product type and desired effect. It can be either appreciated or avoided based on the formulation’s purpose and the user’s expectations. In this case, the product EG01 presented a lower shininess, leaving a more matte effect on the skin, while EG02 and EG03, which are NS, have a more glowy effect on the skin. In this context, the use of active ingredients in the present formulation could be a key factor playing on the shininess and other sensory attributes. Since arginine and N-acetylcysteine are found in high quantities in the formulation, they can direct and influence the emulsifier effect. Indeed, both arginine and N-acetylcysteine can provide a dry, matte finish or oil-absorbing properties similar to those of adding mattifying agents such as inert starch or rice powders described in the literature [58].

Finally, the same Tukey product classification can be observed for the stickiness and the softness attributes among products, with a logical anticorrelation: the less sticky the residual film, the smoother the after-feel. The use of arginine and N-acetylcysteine in this case served dual roles in the cosmetic formulations, functioning not only as active ingredients but also as sensory enhancers, playing not only in lowering shininess, greasiness, and stickiness but also enhancing smoothness. Regarding the sticky character, all products have low stickiness properties (mean values ranging from 1.5 to 2.8 on the ten-point scale), with EG02 presenting statistically significant differences (p-value < 0.05) with two other products. The use of these actives improves the skin’s feel, making it softer and more supple, thereby enhancing the overall texture of the product. This can create a smoother, less tacky feel during and after application. Globally, all products were perceived as smooth on their after-feel, with EG01 and EG03 outlining the highest softness characters. It is interesting to note that comparable softness and stickiness values were highlighted in formulations containing inert starch or rice powders described in the literature [60]. The incorporation of starch particles as emulsion stabilizers can enhance the overall sensory experience by mitigating undesirable sensations such as residual shininess, stickiness, and greasiness. Instead, it promotes a dry, powdery after-feel. Similar effects have been documented for inorganic particles in residual oil films, where these particles alter the characteristics of the film [59,60,61]. In our case, the use of actives like Arginine and N-acetylcysteine not only provides functional skin benefits like antioxidant, hydration, and keratolytic effects, but also acts as sensory enhancers by improving the product’s texture and creating a smoother, more pleasant feel during and after application.

Overall, all the products exhibit appealing sensory properties, including good spreading behavior, fast absorption, low to moderate shininess, minimal stickiness and greasiness, and high smoothness. These qualities are influenced not only by the differences in emulsifiers in the formulation but especially by the significant presence of active ingredients like Arginine and N-acetylcysteine. Among the tested formulations, EG02 exhibited the least favorable outcomes in the sensory evaluation. Consequently, in vivo testing for assessing skin acceptability and tolerance was limited to formulations EG01 and EG03, which showed the most promising overall performance.

3.5. Comparative Screening Test for Checking the Skin Acceptability and Tolerance of Cosmeceutical Products

Out of the three formulas subjected to sensory analysis, two were selected based on their promising results. Consequently, EG01 and EG03 were chosen for further evaluation, specifically due to the tolerance and acceptability tests conducted on human subjects. The investigator observed no new or worsening clinical signs attributable to the products evaluated during the study, which represents an advantage since many products are exhibiting issues in this final evaluation step (

Table 8. The result of acceptability and tolerance for using EG01 and EG03.

Clinical Signs/Sensations of Discomfort (Attributable to the Investigational Formula EG01)			Clinical Signs/Sensations of Discomfort (Attributable to the Investigational Formula EG03)
Reference of the concerned subjects	Description (Date-Type)	%	Reference of the concerned subjects	Description (Date-Type)	%
None	None	0	None	None	0

).

4. Limitations of the Study and Future Testing

One of the key limitations of this study is the lack of full-spectrum stability testing, including chemical degradation analysis, long-term temperature cycling, microbiological evaluation, and packaging compatibility assessments. These tests are essential for determining whether a formulation meets the requirements for a defined shelf life (e.g., ≤30 months or >30 months), and are mandated by international guidelines such as ISO standards and the EU Cosmetic Regulation. In future work, the most promising formulation(s) identified through centrifugation testing will undergo accelerated stability testing, rheological profiling, chemical and microbiological stability assessments, and compatibility studies with packaging materials. These procedures will not only confirm the product’s shelf life and regulatory compliance but will also allow for the determination of the Period After Opening (PAO) and other key consumer safety indicators. The next step will be to subject formulations EG01 and EG03 to extended stability evaluation exceeding 90 days, to investigate their potential long-term stability. To achieve this, standard accelerated stability testing will be conducted under controlled conditions (e.g., 40 °C ± 2 °C/75% relative humidity) for a defined period of time, under ICH and cosmetic industry guidelines [62,63,64,65,66]. Additionally, stress testing protocols will be implemented to simulate real-world and transport-related conditions. These will include temperature cycling tests (exposing samples to alternating low and high temperatures) and freeze–thaw testing, consisting of three cycles of 24 h freezing followed by 24 h thawing. These procedures are critical for identifying hidden instabilities and ensuring the robustness of the formulation throughout its shelf life and distribution chain [67,68,69,70]. Given the high concentration of active ingredients incorporated into the formulations—and considering that not all components were fully soluble in either the lipophilic or hydrophilic phases, with some remaining suspended—this study initially aimed to assess a minimum physical stability period of 90 days. Subsequently, the focus was placed on sensory evaluation, conducted on trained human subjects to determine the acceptability and overall sensory performance of the formulations. Most importantly, in light of the inclusion of a pharmaceutical-grade active compound, N-acetylcysteine, a key objective was to investigate the topical compatibility and tolerability of the product following 28 days of application in a cohort of elderly female participants, a population often characterized by increased skin sensitivity and altered barrier function. For this reason, not all stability tests have yet been performed, as only the most promising formulations, based on preliminary stability and sensory evaluation results, will undergo comprehensive testing. These advanced analyses will be conducted before official product notification and registration as an authorized cosmetic product.

5. Conclusions

It is worth highlighting that sensory analysis represents a highly effective method for the selection of the proposed cosmetic formulations, enabling the early identification of formulations likely to elicit positive or negative responses from end users, thus streamlining the development process. In conclusion, the formulations EG01, EG02, and EG03 exhibited good stability in time, each incorporating a distinct emulsifier: methyl glucose sesquistearate, Ceteareth-20, and polyglyceryl-3-methylglucose distearate. The sensory evaluation, using the descriptive analysis method, highlighted significant differences in sensory profiles between the products. Sensory analysis played a critical role in the selection process of the proposed cosmeceutical formulations, demonstrating its practical value in distinguishing those compositions that best meet patient and consumer expectations. Out of the three tested formulations, only two showed adequate sensory performance, confirming that sensory compatibility is a key prerequisite for product success. Ultimately, for a cosmeceutical product to be effective and well-accepted, it must first deliver a sensory experience that aligns with user expectations, supporting both adherence and perceived efficacy. Across all formulations, appealing sensory properties were observed, including good spreading behavior, rapid absorption, low to moderate shininess (except for EG02, which showed a higher gloss), minimal stickiness and greasiness (with EG02 exhibiting slightly higher values), and a high degree of smoothness. These sensory qualities are influenced by the emulsifiers used, but are particularly enhanced by the significant presence of arginine and N-acetylcysteine. The unique combination of active substances with an anti-wrinkle role is compatible only with emulsion cream bases, and among the three proposed cream formulas, the EG01 and EG03 formulas with methyl glucose sesquistearate and polyglyceryl-3-methyl glucose distearate showed the most promising results from the sensory analysis and the tolerance and acceptability test on human subjects’ point of view. Both EG01 and EG03 stood out, not only for their sensory qualities but also for achieving a 100% tolerance and acceptability rate among a panel of healthy subjects aged 50 to 65.

6. Patents

A part of the presented formulation will be included in a future patent application.