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Retinoid stability and degradation kinetics in commercial cosmetic products
Abstract
Background
Retinoids as dermatological agents are effective against acne, psoriasis, skin aging, and other skin conditions. However, their susceptibility to degradation is a limiting factor for their widespread use.
Objectives
Within this study, we aimed to provide comprehensive and evidence‐based information on retinoid stability and degradation kinetics in commercial cosmetics, focusing on different factors affecting their stability.
Methods
A validated HPLC‐UV methodology was utilized for determination of the most common retinoids in cosmetics (retinol, retinyl palmitate, β‐carotene) and a newer promising retinoid (hydroxypinacolone retinoate). The stability of 16 retinoid derivatives in 12 commercial cosmetics was evaluated within 6 months of long‐term and accelerated stability testing in addition to a one‐week photostability study. Retinoid degradation in the tested formulations followed first‐order kinetics, which was further applied to shelf‐life prediction.
Results
Long‐term and accelerated stability testing revealed retinoid instabilities in almost all products, resulting in a 0%‐80% decline after 6 months at 25°C and a 40%‐100% decline at 40°C, which were kinetically evaluated. Light degradation was more pronounced than temperature‐induced degradation. Among the studied retinoids, the stability of the newer hydroxypinacolone retinoate was the most prominent. This study also identifies correlations between retinoid concentrations, price, formulation, and their stability in cosmetics.
Conclusions
Retinoid instabilities were formulation‐dependent and associated with lower contents than declared in some cosmetics. Retinoid chemical stability and physical stability in topical formulations need to be evaluated by real‐time stability studies, instead of the more frequently used accelerated stability studies.
... The need for stabilization of retinol formulations is well known because of its sensitivity to light, oxygen, heat, and heavy metals [80,92]. A recent study that evaluated the stability of 12 commercially available products with declared retinoids confirmed the instability of retinoids in almost all cosmetic products by long-term and accelerated stability testing [92]. ...
... The need for stabilization of retinol formulations is well known because of its sensitivity to light, oxygen, heat, and heavy metals [80,92]. A recent study that evaluated the stability of 12 commercially available products with declared retinoids confirmed the instability of retinoids in almost all cosmetic products by long-term and accelerated stability testing [92]. It is recommended that retinol in cosmetics is stabilized through appropriate formulation, since retinol in cosmetic formulations is generally stable for less than 6 months if manufactured under an inert atmosphere and stored, for example, in aluminum tubes at 20°C or below [80]. ...
... Considering that such products are not manufactured and stored in this way in practice, the validity of the results from the performed studies is questionable and cannot be attributed solely to the retinol effect [81]. However, the stability of retinoids in cosmetics is formulation-dependent and must be evaluated on a case-by-case basis [92]. In addition, Temova Rakuša et al. [93] evaluated the content-related quality of 35 commercially available cosmetic products containing retinol and other retinoids (mainly retinyl palmitate) and found significant inconsistencies in labeling and deviations from the declared content, e.g., a very low content or a much higher concentration than the maximum concentration recommended by the Scientific Committee on Consumer Safety at the European Commission. ...
Nowadays, numerous skincare routines are used to rejuvenate aging skin. Retinoids are one of the most popular ingredients used in antiaging treatments. Among the representatives of retinoids, tretinoin is considered the most effective agent with proven antiaging effects on the skin and can be found in formulations approved as medicines for topical treatment of acne, facial wrinkles, and hyperpigmentation. Other retinoids present in topical medicines are used for various indications, but only tazarotene is also approved as adjunctive agent for treatment of facial fine wrinkling and pigmentation. The most commonly used retinoids such as retinol, retinaldehyde, and retinyl palmitate are contained in cosmeceuticals regulated as cosmetics. Since clinical efficacy studies are not required for marketing cosmetic formulations, there are concerns about the efficacy of these retinoids. From a formulation perspective, retinoids pose a challenge to researchers as a result of their proven instability, low penetration, and potential for skin irritation. Therefore, novel delivery systems based on nanotechnology are being developed to overcome the limitations of conventional formulations and improve user compliance. In this review, the clinical evidence for retinoids in conventional and nanoformulations for topical antiaging treatments was evaluated. In addition, an overview of the comparison clinical trials between tretinoin and other retinoids is presented. In general, there is a lack of evidence from properly designed clinical trials to support the claimed efficacy of the most commonly used retinoids as antiaging agents in cosmeceuticals. Of the other retinoids contained in medicines, tazarotene and adapalene have clinically evaluated antiaging effects compared to tretinoin and may be considered as potential alternatives for antiaging treatments. The promising potential of retinoid nanoformulations requires a more comprehensive evaluation with additional studies to support the preliminary findings.
... The evaluated commercial cosmetics labelled the presence of different forms of vitamin A (mostly retinyl palmitate, retinol, and β carotene) and vitamin E (tocopherol and tocopheryl acetate), while coenzyme Q10 was only labelled in its oxidized form (ubiquinone) (Figure 1). Despite the lower activity than retinol [14,16], the more stable vitamin A form, retinyl palmitate [24], was the most frequently labelled vitamin A form. Newer vitamin A forms with higher activity and reduced incidence and intensity of irritation side effects are emerging on the market. ...
... The obtained results on the content in relation to the label claims ( Figure 7) revealed significant deviations in both directions-from an absence or significantly lower content than declared up to 4-fold higher contents. Possible explanations for such deviations of the labelled vitamin A contents and the commonly determined active compounds contents below 0.01% include inappropriate formulation or their inappropriate stabilization and degradation during the manufacturing or storage [24]. Regardless, such results are concerning and support our recommendation for their stricter control and regulation, especially as the most significant deviations were observed in the higher-priced cosmetics (Figure 7). ...
Vitamins A and E and coenzyme Q10 are common ingredients in anti-ageing cosmetic products. Within this study, we evaluated the quality of commercial cosmetics with vitamin A (35 products), vitamin E (49 products), and coenzyme Q10 (27 products) by using validated HPLC–UV methods. Vitamin A was determined as retinol, retinyl palmitate, retinyl propionate, β carotene, and hydroxypinacolone retinoate in concentrations ranging from 950 ng/g to 19 mg/g. Total vitamin A contents, expressed with retinol equivalents, ranged from 160 ng/g to 19 mg/g, and were above the maximum concentration recommended by the SCCS in six of the 35 tested cosmetics. The content-related quality control of 10 cosmetics with specified vitamin A content revealed significant deviations (between 0% and 400%) of the label claim. Vitamin E was determined as both tocopherol and tocopheryl acetate in concentrations between 8.5 µg/g and 16 mg/g. Coenzyme Q10 was determined as ubiquinone in 24 tested cosmetics, which labelled it, in concentrations between 4.2 µg/g and 100 µg/g. Labelling irregularities were observed in all three active compound groups, resulting in a significant share (42%) of improperly labelled cosmetic products. The results of this study reveal the need for stricter cosmetics regulation and highlight the importance of their quality control, especially by evaluating the contents of the active compounds, in their efficacy and safety assurance.
... In the present study, the UV absorption peak at 334 nm of PVA/retinol hydrogel confirmed the successful accumulation of retinol in the hydrogel. Like the present study, the maximum absorption peak of retinol was reported at 325 nm [35][36][37]. The shifting peak wavenumber of PVA retinol hydrogel to a higher frequency than PVA hydrogel might be due to the chemical interaction between PVA and the retinol compounds. ...
... In the present study, the UV absorption peak at 334 nm of PVA/retinol hydrogel confirmed the successful accumulation of retinol in the hydrogel. Like the present study, the maximum absorption peak of retinol was reported at 325 nm [35][36][37]. The shifting peak wavenumber of PVA retinol hydrogel to a higher frequency than PVA hydrogel might be due to the chemical interaction between PVA and the retinol compounds. ...
Polyvinyl alcohol (PVA) hydrogels are well-known biomimetic 3D systems for mammalian
cell cultures to mimic native tissues. Recently, several biomolecules were intended for use in PVA
hydrogels to improve their biological properties. However, retinol, an important biomolecule, has not
been combined with a PVA hydrogel for culturing bone marrow mesenchymal stem (BMMS) cells.
Thus, for the first time, the effect of retinol on the physicochemical, antimicrobial, and cell proliferative
properties of a PVA hydrogel was investigated. The ability of protein (3.15 nm) and mineral adsorption
(4.8 mg/mL) of a PVA hydrogel was improved by 0.5 wt.% retinol. The antimicrobial effect of
hydrogel was more significant in S. aureus (39.3 mm) than in E. coli (14.6 mm), and the effect was
improved by increasing the retinol concentration. The BMMS cell proliferation was more upregulated
in retinol-loaded PVA hydrogel than in the control at 7 days. We demonstrate that the respective
in vitro degradation rate of retinol-loaded PVA hydrogels (RPH) (75–78% degradation) may promote
both antibacterial and cellular proliferation. Interestingly, the incorporation of retinol did not affect
the cell-loading capacity of PVA hydrogel. Accordingly, the fabricated PVA retinol hydrogel proved
its compatibility in a stem cell culture and could be a potential biomaterial for tissue regeneration.
... The stability of retinoids has been well studied in the literature, and it is well known that their stability is a common limiting issue in many formulations [36]. In most cases, either in solutions, cosmetic formulations, pharmaceuticals, or commercial products, there is a significant decline in retinoid concentrations at different time intervals [36,37]. To our best knowledge, no studies are available regarding the stability of cyproterone acetate or estriol in topical formulations. ...
Inflammatory skin conditions are prevalent in the general population and are a source of much concern for those who suffer from them. Acne is an extremely common condition and can significantly impact the quality of life of affected patients. Rosacea is another common dermatological disorder that often affects the face and can present with flushing, irritated skin, and pimples. In addition to being key for acne and rosacea, inflammation can also play a role in prematurely aging skin and contributes to the formation of wrinkles. Given the prevalence and patient impact of dermatological conditions on the face, such as those previously described, there is a demand for personalized medicines to manage these conditions when commercially available options are unsuitable, unavailable, or insufficient to fully resolve the condition. When designing an appropriate personalized therapy for a patient, both the vehicle and the active pharmaceutical ingredient choices are key to the success of the treatment. Cleoderm™ is a topical cream designed for use as a vehicle for the preparation of dermatological treatments by compounding pharmacies. Its ingredient profile was specifically curated to be gentle on the skin, allowing its use as a vehicle for compounded preparations that may be applied to sensitive and affected skin. In this bracketed study, benzoyl peroxide, cyproterone acetate, estriol, metronidazole, niacinamide, progesterone, retinoic acid, spironolactone, and tranexamic acid were selected, due to their known applications for dermatological skin conditions. To evaluate the compatibility and stability of Cleoderm™ in these formulations, high-performance liquid chromatography, followed by antimicrobial effectiveness testing, were performed for 180 days. For most formulations, a beyond-use date of 180 days was observed when stored at room temperature, except for retinoic acid, which had a beyond-use date of 30 days. Through the outcomes of this study, we concluded that Cleoderm™ presents increased convenience for both the compounding pharmacist and the patient, suggesting that it is an adequate candidate vehicle for compounding different dermatological formulations with adequate stability, presenting itself as a good alternative to commercially available treatments that cannot be personalized.
... Furthermore, the unstable nature of retinoic acid has also led to a drop in its therapeutic efficacy. This is due to increased liability and decreased stability when exposed to light, heat, oxidation, and changes to environmental pH [104,105]. Ourique et al. (2011) describe the use of a lipidcore polymeric nanocapsules (LCNC) to encapsulate retinoic acid in order to increase the photostability and improve skin retention time. When tested for halflife and effects of photodegradation, the retinoic acid-LCNC achieved a t 1/2 of 26.6 h compared to marketed gel containing retinoid acid which has a t 1/2 of 3.8 h. ...
Hyperpigmentation is a common and major skin problem that affects people of all skin types. Despite the availability of various depigmentation active ingredients for skin hyperpigmentation disorder, none of them are completely satisfactory due to their poor permeability through the skin layer and significant toxicity, thereby causing severe side effects such as irritative dermatitis, erythema, itching, and skin flaking. Nanotechnology plays an important role in advancing the cosmeceutical formulation by improving the solubility, stability, safety, loading efficiency, and dermal permeability of the active ingredients. The aim of this review is to offer a comprehensive discussion on the application of various nanomaterials in improving cosmeceutical formulations used to treat hyperpigmentation. Focus is placed on elucidating the advantages that nanotechnology can bring to some common hyperpigmentation active ingredients such as hydroquinone, arbutin, kojic acid, azelaic acid, and retinoic acid to improve their efficacy in treating hyperpigmentation. Lastly, a total of 44 reported patents and articles of depigmenting compounds encapsulated by nanoparticles were filed and analyzed. Overall, lipid nanoparticles were found to be the most widely used nanomaterial in treating hyperpigmentation.
Graphical abstract
... This product has shown good efficacy in the treatment of onychodystrophy characterized by onychogryphosis [8]. Urea is a hydrating and keratolytic substance [9], keratinase is a proteolytic enzyme that digests keratin [10] and hydroxypinacolone retinoate is a cosmetic grade ester of retinoic acid [11]. It is unique in that it processes innate retinoic acid activity, binding directly with retinoid receptors without the need for metabolic breakdown to more biologically active forms [12]. ...
Lichen planus is chronic inflammatory mucocutaneous disease. Involvement of nails (nail lichen planus: NLP) could be the only manifestation or it could be associated with the other typical skin and mucous localizations. Typical NLP alterations are linear nail bed dyschromia, longitudinal ridging, splitting, onycholysis, and subungual hyperkeratosis. Pterygium could be observed in advanced stages. Treatment of NLP is challenging. Limited clinical data have suggested that both oral and topical retinoids could be beneficial. Recently, a nail lacquer containing urea (20%), keratinase from Bacillus licheniformis, and hydroxipinacolone retinoate (U-KR lacquer) has been available. This product has shown good efficacy in the treatment of onychodystrophy characterized by onychogryphosis. We have evaluated, in a case series pilot study, the efficacy of this lacquer in subjects with moderate NLP. The product was applied once daily on the affected nails. Ten subjects (6 men and 4 women, mean age 38 years) after their written informed consent, with clinical NLP (2 subjects with histological confirmation) affecting foot or hand nails (mean number of nails involved: 4; range from 1 to 10), were treated for 12 consecutive weeks with U-KR, one application per day. The main endpoint was the evolution of a NLP severity score (NLPSS) evaluating 7 nail signs: grade of onycholysis, longitudinal ridging, splitting, grade of subungual hyperkeratosis, nail bed thickening, dyschromia, and nail pitting. For each item, a 4-grade score (from 0: no sign to 3: severe) was used (range of NLPSS from 0 to 21). At baseline, the NLPSS was 20.8 ± 3. After 12 weeks, the NLPSS showed a significant reduction to 4 ± 8.8, representing an 81% reduction in comparison with baseline value (p = 0.0001), with an absolute difference between means of -16.86 ± 2,586 (95% CI of the difference: from -22.49 to -11.22) The product was very well tolerated. This 10-case pilot study suggests that a nail lacquer with 3 components (urea, keratinase, and a retinoid molecule) could be useful in subjects with NLP. Future controlled trials are warranted to better define the therapeutic potential of this product in NLP treatment.
... Retinoids, a class of chemical compounds including retinol, retinal, retinoic acid, and isotretinoin have been used as therapeutic agents for various skin diseases [29]. Topically applied retinoids penetrate the keratinized epidermis rather than the dermis and play a role in changes in keratin synthesis, re ecting the different phases of keratinocyte differentiation and proliferation [20,21]. ...
The current study aimed to characterize the transport kinetics of retinol in fully differentiated human immortalized keratinocyte cells (HaCaT) cultured in trans-well with high-calcium media by measuring the cell integrity of skin barriers, time and concentration dependent transport of retinol, and its metabolites. 25 to 200 µg/mL retinol treatment did not show any significant cytotoxicity in HaCaT. The expression of epidermal differentiation related genes including Keratin 1 (KRT1), Keratin 10 (KRT10), and Involucrin (IVL) significantly increased in HaCaT cells cultured with high-calcium media (2.8 mM) compared to low calcium (0.03 mM). There was no significant decrease in TEER value after incubating retinol (10 to 100 µg/mL) compared to control (p > 0.05), indicating that retinol tends to maintain strength and integrity of the epidermal barrier. The maximum epidermal migration of retinol from apical to basal media occurred from incubation of 75 µg/mL retinol, indicating that it was not concentration dependent. The area under the curve (AUC) of mAU*min for the unknown peak found in basal media for 600 min increased in a concentration dependent pattern, showing 10.23 ± 0.16 and 72.73 ± 30.86 at 10 and 100 µg/mL of retinol treated in apical, respectively. The metabolite having a precursor ion (m/z 325.83 [M + H + Na] ⁺ ) in the spectrum was identified as a retinoic acid (m/z 301.3 [M + H] ⁺ ) with sodium adduct. Results from the current study suggest that optimal concentration of retinol and treatment time in human keratinocytes could enhance the conversion of retinol to retinoic acid, promoting dermatological use of retinol.
... Another major factor affecting retinol degradation is light (Failloux et al., 2004;Temova Rakuša et al., 2021). ...
Retinol is a fat-soluble vitamin A that is widely used in the food and pharmaceutical industries. Currently, retinol is commercially produced by chemical synthesis. Microbial production of retinol has been alternatively explored but restricted to a mixture of retinoids including retinol, retinal, and retinoic acid. Thus, we introduced heterologous retinol dehydrogenase into retinoids mixture-producing Saccharomyces cerevisiae for the selective production of retinol using xylose. Expression of human RDH10 and Escherichia coli ybbO led to increases in retinol production, but retinal remained as a major product. In contrast, S. cerevisiae harboring human RDH12 produced retinol selectively with negligible production of retinal. The resulting strain (SR8A-RDH12) produced retinol only. However, more glycerol was accumulated due to intracellular redox imbalance. Therefore, Lactococcus lactis noxE coding for H2O-forming NADH oxidase was additionally introduced to resolve the redox imbalance. The resulting strain produced 52% less glycerol and more retinol with a 30% higher yield than a parental strain. As the produced retinol was not stable, we examined culture and storage conditions including temperature, light, and antioxidants for the optimal production of retinol. In conclusion, we achieved selective production of retinol efficiently from xylose by introducing human RDH12 and NADH oxidase into S. cerevisiae.
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... They are composed of three structural moieties: a β-ionone ring, an isoprenoid backbone, and a functional group such as an alcohol (retinol), an aldehyde (retinal), a carboxylic acid (retinoic acid), or an ester group (retinyl esters) [3]. In a biotechnological aspect, retinoids are used as a dermatological agent against acne, psoriasis, skin aging, and other skin conditions [4]. ...
Microbial production of bioactive retinoids, including retinol and retinyl esters, has been successfully reported. Previously, there are no reports on the microbial biosynthesis of retinoic acid. Two genes (blhSR and raldhHS) encoding retinoic acid biosynthesis enzymes [β-carotene 15,15’-oxygenase (Blh) and retinaldehyde dehydrogenase2 (RALDH2)] were synthetically redesigned for modular expression. Co-expression of the blhSR and raldhHS genes on the plasmid system in an engineered β-carotene-producing Escherichia coli strain produced 0.59 ± 0.06 mg/L of retinoic acid after flask cultivation. Deletion of the ybbO gene encoding a promiscuous aldehyde reductase induced a 2.4-fold increase in retinoic acid production to 1.43 ± 0.06 mg/L. Engineering of the 5’-UTR sequence of the blhSR and raldhHS genes enhanced retinoic acid production to 3.46 ± 0.16 mg/L. A batch culture operated at 37 °C, pH 7.0, and 50% DO produced up to 8.20 ± 0.05 mg/L retinoic acid in a bioreactor. As the construction and culture of retinoic acid–producing bacterial strains are still at an early stage in the development, further optimization of the expression level of the retinoic acid pathway genes, protein engineering of Blh and RALDH2, and culture optimization should synergistically increase the current titer of retinoic acid in E. coli.
... No significant decomposition is measured. [43][44][45] The experiments showed that addition of the nanoparticles, of Ca-polyP-NP with embedded tretinoin, to the virus-mimicking liposomes causes a destruction/fragmentation of the envelope protein supplemented liposomes. ...
The SARS-CoV-2 infection is transmitted by respiratory droplets. We have introduced a new concept of masks, which comprises a threefold mode-of-action: trapping of the virus particles, blocking of the viruses, and finally killing of the viruses.
The current study aimed to characterize cellular uptake and bioconversion of retinol in fully differentiated human immortalized keratinocytes cells (HaCaT) and artificial skin by measuring the cell integrity of skin barriers, time dependent transport of retinol, and bioconversion to its metabolites. The expression of epidermal differentiation related genes including Keratin 1 (KRT1), Keratin 10 (KRT10), and Involucrin (IVL) significantly increased in differentiated HaCaT. TEER of HaCaT did not decrease after incubating retinol compared to control (p>0.05), indicating that retinol tends to maintain strength and integrity of epidermal barrier. TEER of artificial skin decreased treatment of retinol for 2 hrs, but it was recovered after 4 hrs. During retinol transport, metabolite was eluted at 13.37 and 13.82 min of basal medium of both keratinocytes and artificial skin, which was identified as retinoic acid by product ion of m/z 283.47. Retinol appeared to be accumulated in keratinocytes, but its uptake tends to be reduced in a time dependent manner. Retinoic acid converted from retinol in keratinocytes was time dependently transported. In case of artificial skin, retinol was mostly found in apical at initial incubation time, but it was reduced during incubation for 24hrs. Retinoic acid was time‐dependently found in a basal, which was converted via epidermis‐dermis. Results from the current study suggest that topical application of retinol to human skin optimal concentration and time exposure could maintain epidermal barrier function and promote skin function due to its remarkable bioconversion to retinoic acid in the epidermis‐dermis.
Background:
Individual B vitamins have many favourable effects on the skin and are common cosmetic ingredients. However, their formulation is demanding due to stability issues, which consequently affect the products´ quality.
Aims:
We aimed to determine the quality (labelling accuracy, content determination, and content-related quality control) and stability under long-term and accelerated storage conditions of a representative sample of commercial cosmetics containing the most common B vitamins - nicotinamide, dexpanthenol, pyridoxine, and cyanocobalamin.
Methods:
Cyanocobalamin was determined by a previously published stability-indicating HPLC-DAD method for the simultaneous determination of all hydrophilic vitamins. This method was additionally simplified and adjusted for the time-effective analysis of nicotinamide, dexpanthenol, and pyridoxine. Both methods were properly validated.
Results:
All labelled B vitamins were present in the 36 tested products, mostly in contents, reported effective on the skin. Thus, a straightforward correlation between vitamin contents and product prices was not observed. The content-related quality control of eight products, which quantitively specify their content, revealed significantly lower nicotinamide contents (47% and 57%) in two products and appropriate or higher nicotinamide (102-112%) and dexpanthenol (100-104%) contents than declared in the remaining products. The 6-month long-term and accelerated stability studies demonstrated the products' physical stability, but also revealed dexpanthenol, pyridoxine, and cyanocobalamin degradation, while nicotinamide was mostly stable in the tested products.
Conclusions:
The obtained results provide an inside into the quality of commercial vitamin B cosmetics and highlight the importance of stability testing in the formulation of quality, efficient and safe cosmetics.
Vitamin A is the first vitamin approved by the Food and Drug Administration as an anti-wrinkle agent that changes appearance of the skin surface and has anti-aging effects. Vitamin A is in a group of fat-soluble substances and belongs to the category of retinoids. Apart from retinol, that group includes structurally related substances with the biological properties of retinol. Since the biological activity of the substances differs, for the purpose of standardization, it is given in retinol equivalents. Vitamin A and its derivatives are among the most effective substances slowing the aging process. Retinoids regulate the cell apoptosis, differentiation and proliferation. Anti-wrinkle properties of retinoids promote keratinocytes proliferation, strengthen the protective function of the epidermis, restrain transepidermal water loss, protect collagen against degradation and inhibit metalloproteinases activity. Retinoid activity is related to high affinity for nuclear receptors: RAR - retinoid acid receptors and RXR - retinoid X receptors.
Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.
Skin becomes thin, dry, pale, and finely wrinkled with age. Retinoids are a large class of compounds that are important in modern therapy for dermatological treatment of wrinkled skin. Of the retinoids, retinol and vitamin A palmitate are thought to induce thickening of the epidermis and to be effective for treatment of skin diseases. Accordingly, α-lipoic acid or the reduced form, dihydrolipoate, are potent scavengers of hydroxyl radicals, superoxide radicals, peroxyl radicals, singlet oxygen, and nitric oxide with anti-inflammatory properties (1). Cosmetic ingredient stability prediction relies on kinetic quantitative chemical analysis of active components at different temperatures. Vitamin A palmitate and α-lipoic acid, are known to be unstable to light or heat (2). The aims of this study were to evaluate the stability of α-lipoic acid and vitamin A palmitate in the presence of vitamin E (acetate) and other antioxidants in lipophilic/hydrophilic medium (O/W emulsions) at pH 3.0, 5.0, and 7.0. The formulations that were investigated contained 0.12% (w/w) vitamin A palmitate, 0.4% (w/w) vitamin E acetate, and 0.5 % α-lipoic acid (formulation A), supplemented with ascorbyl palmitate, magnesium ascorbyl phosphate, and vitamin C (formulation B) or with butylhydroxytoluene (BHT, formulation C) or ascorbyl palmitate (formulation D). The chemical analyses of α-lipoic acid and vitamin A palmitate were carried out by HPLC. Formulations C and D at pH 7.0 were selected as the most stable for these components. The purpose of this paper is the selection of the most stable formulations for their application in in vivo studies.
Sunlight is a known human carcinogen. Many cosmetics contain retinoid-based compounds, such as retinyl palmitate (RP), either to protect the skin or to stimulate skin responses that will correct skin damaged by sunlight. However, little is known about the photodecomposition of some retinoids and the toxicity of these retinoids and their sunlight-induced photodecomposition products on skin. Thus, studies are required to test whether topical application of retinoids enhances the phototoxicity and photocarcinogenicity of sunlight and UV light. Mechanistic studies are needed to provide insight into the disposition of retinoids in vitro and on the skin, and to test thoroughly whether genotoxic damage by UV-induced radicals may participate in any toxicity of topically applied retinoids in the presence of UV light. This paper reports the update information and our experimental results on photostability, photoreactions, and phototoxicity of the natural retinoids including retinol (ROH), retinal, retinoid acid (RA), retinyl acetate, and RP (Figure 1).
Background
Retinoids are widely used in different cosmetic products because of general improvement of skin appearance. However, retinoid concentration in cosmetics is restricted, and one particular form – retinoic acid is banned in cosmetics due to safety reasons.
Objectives
Within this study, we aimed to examine the quality of a considerable number of commercial retinoid cosmetic products in terms of their content and labelling, including also screening for the presence of retinoic acid.
Methods
An appropriate analytical methodology, based on HPLC‐UV for the simultaneous determination of common retinoids, along with a screening method for retinoic acid, was developed and validated. Structural identity confirmation of the newer retinoid ‐ hydroxypinacolone retinoate was performed by LC‐MS.
Results
Retinol and retinyl palmitate were most often found, in concentrations mostly below 0.3%, and up to 1.3% retinol equivalents. Determined contents deviated significantly from the quantitatively declared ones in seven products (0‐130%). In more than half of the tested products, inconsistencies between the contained and labelled retinoid were noticed. These products, as well as in 14 additional anti‐age cosmetics, were screened for retinoic acid, which was detected in two products.
Conclusions
The obtained results from retinoids assay in commercial cosmetic products confirmed that the proposed method is appropriate for their routine analysis. The presence of retinoic acid in two products and determined retinoid contents above the Scientific Committee on Consumer Safety recommendations in 20% of the tested cosmetics reveal the need for their more strict regulation and quality control to ensure their efficacy and safety.
Introduction:
Three original cosmetic formulations containing retinol as an active component with liquid crystal, lamellar, and lipid bases were prepared. The formulas contain different concentrations of retinol, that is, 0.5%, 0.3%, and 0.15%.
Objectives:
The aim of the study was to evaluate a spectrophotometric method for assessing the quantity of retinol in the nine cosmetic products and to determine the viscosity of each formula.
Materials and methods:
The formulations were tested for stability; final product testing was preceded by sample weighing and pH measurement as well as exposure to the light source from xenon lamp that maps solar radiation in the range of 310-800 nm. Microbiological purity test was performed according to the PN-EN ISO 29621:2011 method and viscosity carried out using a cone-plate digital rheometer (DV-III Brookfield, version 3.0) on 0.5 cm3 emulsion samples at 32°C. The retinol content in preparations was assayed by UV spectrophotometry.
Results:
Each of prepared cosmetic products with retinol storing in a room temperature occurred to be stable. The liquid crystal emulsion has the higher viscosity than lamellar and lipid emulsions. Although the retinol concentration in lipid serum was determined with high accuracy, the method has some limitations associated with differences between the lipid cosmetic base and the lamellar and liquid crystal sera. Nevertheless, the UV spectrophotometric method described herein is a simple and highly accurate approach for determining the retinol content in lipid cosmetics: Its coefficient of correlation was R2 = 0.9982 with a relative standard deviation (n = 3) in the range of 0.5%-1.5%.
Conclusion:
The presented UV spectrophotometric method represents an effective tool for fast and accurate determination of retinol content in lipid formulations. Probably, the method could be used in studies of other retinol-based preparations, for example, medications, and for determining the effective life of retinol-containing products in storage.
This study was performed to examine the stability of retinol contained within oil-in-water (O/W) emulsions under UV and during storage at different temperatures. O/W emulsions were prepared using different emulsifiers and oil concentrations. The stability of the retinol contained in the O/W emulsions was investigated by measuring the percentage of residual retinol in the samples after UV exposure and storage at different temperatures (4, 25, and 40 °C). The oil concentration of the emulsion had a greater impact on UV stability than the type of emulsifier used, whereas the storage stability at different temperatures was affected by both the choice of emulsifier and the oil concentration. The storage stability of the retinol contained in the O/W emulsions may be related to the lipid oxidation properties of the emulsions rather than the latter's physical stability. Experiments with EDTA and different oil types were performed to confirm this theory.
Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.
J. Cosmet. Sci., 60, 485–500 (September/October 2009)
Retinol and retinyl palmitate are frequently used in cosmetic products. A simple, rapid, and sensitive reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection was developed for the quantitation of retinol, retinyl palmitate, and retinoic acid in cosmetic preparations. The analytes were extracted from a cosmetic/Celite mixture using a solvent system composed of equal amounts of hexane, isopropanol, and ethyl acetate, and the extract was injected directly into an HPLC chromatograph with a C18 column and UV detector set at 330 nm. Chromatographic separation was achieved by gradient elution with a mobile phase, starting with aqueous ammonium acetate buffer/methanol that was gradually changed to methanol/dichloromethane. The average recoveries of retinol, retinyl palmitate, and retinoic acid from spiked cosmetic products were 95% or higher. In a survey of 29 consumer cosmetic skin care products labeled to contain retinoids, most products were found to contain either retinol or retinyl palmitate at concentrations up to 2.2% (w/w), while a few products contained both ingredients. A number of products also contained cis isomers of retinol that could be quantitatively distinguished from the all-trans compound. The method can be used to quantitate several retinoids and their isomers in cosmetic products. The method will be useful for obtaining information needed to estimate levels of exposure to retinoids from cosmetic products.
The influence of silica nanoparticle coating on the chemical stability and phase distribution of all-trans-retinol in submicron oil-in-water emulsions is reported. The chemical stability was studied as a function of UVA+UVB irradiation, and storage temperature (4 degrees C, ambient temperature, and 40 degrees C) for emulsions stabilised with lecithin and oleylamine as the initial emulsifier with and without silica nanoparticle layers. The chemical stability of all-trans-retinol was highly dependent on the emulsifier type and charge, with negligible influence of the initial loading phase of silica nanoparticles. A significant stability improvement (approximately 2-fold increase in the half-life of the drug) was observed by nanoparticle incorporation into oleylamine-stabilised droplets (i.e. electrostatically coated), with no considerable effect for partially coated lecithin-stabilised droplets. The chemical stability of all-trans-retinol incorporated into nanoparticle-coated emulsions was well-correlated to the phase distribution of the active agent, and the interfacial structure of emulsions as determined by freeze fracture-SEM. Specifically engineered nanoparticle layers can be used to enhance the chemical stability of active ingredients in emulsion carriers.
In all-in-one admixtures (AIOs), vitamins can be degraded and lipid can be peroxidized by light exposure, oxygen action, and multiple chemical interactions.
We investigated the impact of three commercial lipid emulsions and two multivitamin preparations on vitamin A and vitamin E chemical stability and lipid peroxidation potential of AIOs.
A soybean oil (Soy), soybean/medium-chain triacylglycerol oil (MCT), and olive/soybean oil (Olive)-based emulsion (all 20%), and a lyophilized (Lyo) and emulsified (Emu) multivitamin compounds, were tested. Two AIOs for each lipid emulsion were prepared, the former with Lyo and the latter with Emu. The concentrations of retinol palmitate, alpha-gamma-delta-tocopherol, and malondialdehyde were analyzed in AIOs, immediately (T0) and 24 hours (T24) after compounding.
Retinol palmitate, and alpha- and gamma-tocopherol were more stable in MCT-AIOs than in both Soy-AIOs and Olive-AIOs (p < 0.013; p < 0.001 respectively). Furthermore alpha-tocopherol was more stable in Lyo-AIOs than in Emu-AIOs (p < 0.004). Malondialdehyde (MDA) increased differently among the admixtures; however the concentrations were similar in all AIOs at T24.
The differences in retinol palmitate stability were due both to lipid emulsions per se and to interaction between lipid emulsions and multivitamin preparations. The alpha-gamma-tocopherol stability depended on both lipid emulsions and multivitamin preparations. In tested AIOs there was a different degradation rate of fat-soluble vitamins to keep the same lipid peroxidation level, since MDA concentrations at T24 were similar among AIOs.
Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.
Vitamin E acetate is often used rather than vitamin E as an ingredient of skin care products and dermatological preparations, because it lacks the free phenolic OH group. However, because of this the acetate as such is biologically inactive. In spite of this intrinsic inactivity, the skin is protected against the harmful effects of sunlight after topical application of vitamin E acetate. Therefore it is supposed that hydrolysis takes place in the skin and that the reaction product, the radical scavenger vitamin E, is responsible for the protection observed. In this in vivo study with the rat, we have investigated the hydrolysis of RRR-alpha-tocopheryl acetate (vitamin E acetate) in the epidermis in relation to UV radiation protection. (As a measure of protection, we used the UV-induced binding of 8-methoxypsoralen to epidermal biomacromolecules.) After a period of 5 h from a single application of vitamin E acetate, hydrolysis into free vitamin E was not observed. No protection was found at this time point, corresponding with the absence of vitamin E. After treatment for 5 days, consisting of one topical application daily, the percentage of acetate present in the stratum corneum which was hydrolysed into free vitamin E was less than 1%, whereas the corresponding value for the viable layer of the epidermis was about 5%. The hydrolysis of vitamin E acetate in the epidermis proceeded very slowly. As a result, the absolute amount of free vitamin E, found in the total epidermis after treatment for 5 days with the acetate, was only a few times higher than the normal level. Yet, this very small amount of free vitamin E proved to be sufficient for maximal protection in this animal model. The results show that vitamin E acetate acts as a prodrug, which very slowly releases minute amounts of active vitamin E.
The degradations of 13-cis-retinoic acid and all-trans-retinoic acid in an organic solvent were determined with an HPLC assay. The degradation curves at 70, 50 and 37 degrees C all showed autocatalytic characteristics for both isomers. For this kind of complex reaction, the usual method cannot be used to estimate the shelf-lives and half-lives at room temperature. In this work a new method was developed to directly calculate the shelf-lives and half-lives. From this equation the activation energy was found to change as the multiple step reaction progressed.
The goal of this study was to compare vitamin A, E, C, B12, B2 and folic acid concentrations in parenteral nutrition solutions in multilayer and single layer EVA bags. Two different bag trade marks were used: Bexen and Miramed. We measured vitamin concentrations at 24 hours, the fifth and seventh day after refrigerated storage and the eighth day after 24 hours at room temperature. Trace-element and temperature influence were studied. Vitamins A, E, B12, B2 and folic acid had a similar behaviour with multi-layer and one-layer bags. No differences were observed between solutions with and without trace-elements. The concentrations remained within acceptable ranges. We observed a clear decrease of vitamin C, that can be avoided with the use of multilayer bags. These bags can be useful in home parenteral nutrition or when vitamins cannot be added immediately before its administration. An important loss of vitamin A was also detected in parenteral nutrition solutions without lipids, both in multilayer and single layer bags, despite photoprotection and refrigeration.
13-Cis retinoic acid (Accutane) was extracted from a cream, gel, capsule and beadlet dosage from using supercritical carbon dioxide modified with 5% methanol as the mobile phase. The pump pressure and the extraction chamber and restrictor temperature were experimentally optimized at 325 atm and 45 degrees C, respectively. A 2.5-min static and 5-min dynamic extraction time were used. The supercritical fluid extraction (SFE) eluent was trapped in methanol, injected into the high-performance liquid chromatographic (HPLC) system, and quantitated by ultraviolet detection at 360 nm. Application of the SFE method to spiked placebo dosage forms gave 13-cis retinoic acid recoveries of 98.8, 98.9, 98.8 and 100% for the cream, gel, capsule and beadlet, respectively, with R.S.D.s in the range 0.6-0.9% (n = 4). Inter-day percent error and precision of the extraction were 1.1-2.0 and 0.2-2.4% (n = 3), respectively, and intra-day percent error and precision were 1.0-3.0 and 0.3-2.1% (n = 8), respectively. Percent error and precision data for spiked celite samples in the 0.05-1.0 microgram ml-1 range were 0.59-4.75 and 1.8-2.1% (n = 3), respectively. The extraction method was applied to commercial 13-cis retinoic acid dosage forms and the results compared to unextracted samples. Linear regression analysis of concentration versus peak height gave a correlation coefficient of 0.9991 with a slope of 7.468 and a y-intercept of 0.1923. The percent error and precision data were 1.3-5.3 and 0.2-1.5% (n = 4), respectively. The photoisomers of 13-cis retinoic acid were also extracted with the method and recoveries of 90.4-92.4% with R.S.D.s of 1.5-3.4% were obtained (n = 4).
Liquid chromatographic (HPLC) methods with fluorescence detection at different wavelengths were developed for measurements of retinoic acids (13-cis and all-trans) in pharmaceutical dosage forms and components of 'retinoid solution' (all-trans retinoic acid, vitamin A palmitate and beta-carotene), a galenical of 'Di Bella therapy', using reversed phase columns under isocratic conditions. The stability of all-trans retinoic acid in cream and all-trans retinoic acid and vitamin A palmitate in 'retinoid solution' was investigated. Solid-phase extraction (SPE), using C18 sorbent was applied to the analysis of retinoic acids (9-cis, 13-cis and all-trans) in the 'retinoid solution' to obtain a practical and reliable sample clean-up. The results showed that these preparations (cream and solution) can be conveniently stored in the dark (t.a. or 2-8 degrees C): under these conditions about 86-87% of the all-trans retinoic acid initial concentration in both formulations and about 73-78% of vitamin A palmitate in the 'retinoid solution' remained after 90 days, while under sunlight exposure rapid degradation of the drugs was observed.
Vitamins A and E are the most light-sensitive vitamins. Vitamin A is degraded by photolysis, while vitamin E degrades by photo-oxidation. The composition of the parenteral nutrition mixture and the container could therefore influence degradation during daylight administration. The aim of this study was therefore to determine the influence of fat emulsion and the type of bag on the photo-degradation of vitamins A and E in Parenteral Nutrition (PN) mixtures during simulated infusion in daylight.
Representative adult PN mixtures, with and without fat emulsion, were prepared. Samples for analysis were taken from infusates and each bag during simulated infusion. Degradation of vitamins A and E was determined by stability-indicating HPLC analysis.
Results indicated that vitamin A loss proceeded rapidly during infusion, resulting in up to 80% loss in 6 hours, even with light protection of the bag. The presence of fat emulsion did not provide significant light protection. Vitamin E degradation was substantial if mixtures were prepared in EVA bags but was largely prevented if PN mixtures were compounded and stored in multi-layered bags.
It is recommended that all PN bags should be light-protected during infusion in daylight. The use of multi-layered bags will prevent vitamin E losses during infusion.
Vitamin A and vitamin A palmitate photostability were tested in different media. Ethanol and octyl octanoate solutions of these two vitamins, as such and with the addition of sunscreens (3,4 methylbenzilidencanfora, butyl methoxy dibenzoylmethane and octyl methoxycinnamate) or beta-carotene and butylated hydroxy toluene, were analysed spectrophotometrically after UVB or UVA irradiation. An O/W fluid emulsion with 0.5% w/w of retinyl palmitate, with and without butylated hydroxy toluene, was prepared. The oil containing the vitamin was extracted with HCl and aluminium sulfate and analysed spectrophotometrically after UVB or UVA irradiation. The fluid emulsion containing retinyl palmitate with and without butylated hydroxy toluene was stored at different temperatures and analysed every week spectrophotometrically for a month. Of the sunscreens tested butyl methoxy dibenzoylmethane showed the strongest protective action towards vitamin A and vitamin A palmitate, whereas beta-carotene did not protect either vitamin. Butylated hydroxy toluene inhibited the photodegradation of both vitamins dissolved in octyl octanoate, suggesting that oxygen may be involved in their degradation. O/W emulsion promoted slightly the degradation of vitamin A ester. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light and heat.
Vitamin A palmitate photostability in relation to UVA and UVB was tested in hydroxy ethyl cellulose hydrogels at pH 4.0, 5.6, 7.0, and 8.0, alone and with the addition of sunscreens (3,4-methylbenzilidencamphor or butyl methoxy dibenzoylmethane) or an antioxidant (butylated hydroxy toluene). The photostability of vitamin A palmitate was also tested in encapsulated systems (Tagravit A1 microcapsules, Lipotec liposomes, phosphatidylcholine liposomes, and Lipotec nanocapsules) dispersed in gels at pH 5.6 and 7.0. The stability of retinyl palmitate over time in hydroxy ethyl cellulose hydrogels at pH 5.6 and 7.0 (stored one month at 25 degrees C or 40 degrees C), alone or with butylated hydroxy toluene, was also tested. The stability of retinyl palmitate over time in encapsulated systems, dispersed in gels at pH 5.6 and 7.0, was also studied. O/W emulsions were also prepared to compare the stability of vitamin A palmitate introduced in a lipophilic/hydrophilic medium (O/W emulsions) and a hydrophilic medium (hydrogels). HPLC analysis showed that encapsulated systems such as Lipotec nanocapsules, Tagravit A1 microcapsules, phosphatidylcholine liposomes, and Lipotec liposomes protect the vitamin A ester over time from hydrolysis and from oxidation to retinaldeide and retinoic acid, and that Lipotec nanocapsules and phosphatidylcholine liposomes also improve the vitamin's photostability. A change in pH (from 5.6 to 7.0) of the gels did not influence the vitamin ester's stability. pH levels of 4.0 and 8.0 determined a decrease in the stability of retinyl palmitate in the gels. A high concentration of sunscreens improved the photostability of retinyl palmitate in the gels at pH 5.6 and 7.0. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light at all the pH levels studied and by heat at pH 5.6 and 7.0, as can be seen from the study of the photostability of vitamin A palmitate under UVB and UVA and of stability over time. Rheological studies showed a slight decrease in the viscosity of the gels after UVB-UVA irradiation and a higher decrease in the viscosity of the gels and the emulsions after storage at 25 degrees C and 40 degrees C. This decrease can be attributed to a partial degradation of hydroxy ethyl cellulose and of emulsifier, as can be seen from the decrease in shear stress versus shear rate values under these conditions of storage, denoting a depolymerization of the rheological modifier.
Cosmetic stability prediction relies on quantitative chemical determinations of active components after certain times and in different temperatures. However, physical stability, an important parameter in skin care products is not considered in these conditions. This study proposes the determination of cosmetic stability chemical and physical parameters validated by (HPLC) chromatography and rheological measurements, respectively, using a gel-cream containing retinyl palmitate and tocopheryl acetate as a model system. The predicted shelf life addresses both the physical and chemical aspects of the system. Results emphasize the importance of studying both parameters by showing the relation of components degradation and physical stability. Moreover, they contribute to an improved understanding of physical and chemical stability aspects of cosmetic formulations, mainly if they contain Vitamins A and E derivatives.
Two commercial anti-aging products, RETI C and RETI C concentrate emulsions, containing retinol and vitamin C, were studied. The concentration of vitamin A was determined over time, subjecting the creams to an accelerated stability test. Both emulsions, when stored at 25 degrees C, showed a moderate decrease over time in retinol concentration, while after storage at 40 degrees C the percentage of retinol degraded increased over time. Under UVA irradiation, the retinol degraded to a greater extent than under UVB irradiation, both in RETI C and RETI C concentrate emulsions. In order to verify the anti-aging effectiveness of the emulsions, an in vivo test on some female volunteers was carried out, evaluating the visible results of the application of the creams on the skin surface. The creams were rather unstable after storage at 40 degrees C, but they were effective in treating the signs of aging and in reducing facial wrinkles.
Retinol (ie,vitamin A) is commonly used in dermatology as an adjunct to treat rhytids, acne,and dyschromia. However, vitamin A and many of its derivatives have poor photostability and are unstable in the presence of oxygen.
We aimed to assess the stability of retinol under simulated patient application conditions in a commercially available hydroquinone 4% cream containing retinol 0.3%, avobenzone (ultraviolet-A sunscreen), octinoxate (ultraviolet-B sunscreen), vitamins C and E (antioxidants), and moisturizers.
One gram of the preparation was applied as a thin film to the inside base of 4 groups of four 100-mL wide-mouthed beakers, incubated in a 37+/-2 degrees C water bath. Each experimental group consisted of 4 beakers for assays at 0.5,1,2,and 4 hours. The samples were exposed to varying combinations of full spectrum light and headspace gas (air or inert nitrogen gas [N2 ]). Retinol content was assayed via high-pressure liquid chromatography using a 1:9 water:methanol solvent system. The control group (group 5) was not exposed to full-spectrum light or headspace gas but served for comparative purposes.
On exposure to light and room air, retinol stability was 94.4% at 0.5 hour, 94.8% at 1 hour, 92.4% at 2 hours, and 91.5% at 4 hours. The retinol contained in the preparation was stable for >or=4 hours. Samples exposed to light and N 2 gas demonstrated 96.5% and 91.3% stability at 0.5 hour and 4 hours exposure times, respectively. Samples that were not exposed to light had a stability of 99.2% (group 3, exposed to air) and 96.9% (group 4, exposed to N(2)) of the initial retinol present after 4 hours.
The retinol in the hydroquinone 4%/ retinol 0.3% cream with antioxidants and sunscreens underwent <10% degradation under simulated-use conditions, including exposure to UV light, oxygen, and body temperature.
Stability of cosmetic formulations containing esters of vitamins E and A: chemical and physical aspects
- T Guaratini
- MD Gianeti
- PMBGM Campos
Guaratini T, Gianeti MD, Campos PMBGM. Stability of cosmetic
formulations containing esters of vitamins E and A: chemical and
physical aspects. Int J Pharm. 2006;327:12-16.
Stability of Vitamins in Pharmaceutical Preparations‐A Review
- Kondepudi N
Kondepudi N. Stability of Vitamins in Pharmaceutical Preparations-A
Review. Int J Res Appl Sci Eng Technol. 2016;4:499-503.
Photodecomposition and phototoxicity of natural retinoids
- W Tolleson
- S Cherng
- Q Xia
- M Boudreau
- J Yin
- E Al
Vitamin A and vitamin E isoforms stability and peroxidation potential of all‐in‐one admixtures for parenteral nutrition
- M Guidetti
- A Sforzini
- G Bersani
- C Corsini
- G Grossi
- E Al