Topical Semisolid Drug Product Critical Quality Attributes with Relevance to Cutaneous Bioavailability and Pharmacokinetics: Part I-Bioequivalence of Acyclovir Topical Creams.

PURPOSE: To develop a toolkit of test methods for characterizing potentially critical quality attributes (CQAs) of topical semisolid products and to evaluate how CQAs influence the rate and extent of active ingredient bioavailability (BA) by monitoring cutaneous pharmacokinetics (PK) using an In Vitro Permeation Test (IVPT). METHODS: Product attributes representing the physicochemical and structural (Q3) arrangement of matter, such as attributes of particles and globules, were assessed for a set of test acyclovir creams (Aciclostad® and Acyclovir 1A Pharma) and compared to a set of reference acyclovir creams (Zovirax® US, Zovirax® UK and Zovirax® Australia). IVPT studies were performed with all these creams using heat-separated human epidermis, evaluated with both, static Franz-type diffusion cells and a flow through diffusion cell system. RESULTS: A toolkit developed to characterize quality and performance attributes of these acyclovir topical cream products identified certain differences in the Q3 attributes and the cutaneous PK of acyclovir between the test and reference sets of products. The cutaneous BA of acyclovir from the set of reference creams was substantially higher than from the set of test creams. CONCLUSIONS: This research elucidates how differences in the composition or manufacturing of product formulations can alter Q3 attributes that modulate myriad aspects of topical product performance. The results demonstrate the importance of understanding the Q3 attributes of topical semisolid drug products, and of developing appropriate product characterization tests. The toolkit developed here can be utilized to guide topical product development, and to mitigate the risk of differences in product performance, thereby supporting a demonstration of bioequivalence (BE) for prospective topical generic products and reducing the reliance on comparative clinical endpoint BE studies.

Heatmap Evaluation of Facial Hydration Using a Novel Python Program.

BACKGROUND: Evaluating cleansers and moisturizers provides important information to guide clinicians in the recommendation of these products. This project was performed to visualize skin hydration via heatmap after the use of a gentle skin cleanser (GSC) and moisturizing lotion (ML). METHODS: Half-face, intra-individual open-label study in healthy volunteers. Cleanser was administered in a single application that was then wiped off the face. Moisturizing lotion was applied at least once-daily for one week. Hydration measurements were made at 30 pre-defined points on half of the face, at baseline, and 30 minutes post-application; an additional assessment at week 1 was made for the moisturizing lotion. Heatmaps were generated using Python programming software to interpolate hydration values to colors that were then superimposed onto the volunteer's facial image.  Results: Five subjects completed the cleanser assessments, and 5 subjects completed the 30-minute evaluation for the lotion, with 4 completing the week 1 assessment. There was a visible shift in skin hydration post-GSC application from values approximately in the 12-42 AU (arbitrary unit) range to 30-60 AU at 30 minutes. Similarly, there was a shift in hydration from baseline to 30 minutes that continued to increase through week 1 of ML use. CONCLUSIONS: This innovative heatmap data generation showed a clear, visual change in hydration over time. There was a visible shift in hydration values from baseline to 30 minutes after application of cleanser; hydration also improved after use of moisturizing lotion at 30 minutes and increased after week 1 application.  J Drugs Dermatol. 2024;23(6):463-465.     doi:10.36849/JDD.8221.

INDIVIDUAL ARTICLE: Real-World Patient Cases Using Triple Lipid-Containing Cream for Cutaneous Healing Post Laser or Microneedling Radiofrequency Treatment.

Lipids play an essential role in skin barrier health. With age, there is a natural reduction of physiological lipids such as fatty acids, ceramides, and cholesterol. The triple lipid restore cream is a moisturizer that contains an optimized lipid ratio for aging skin. The cream contains a 2:4:2 ratio of ceramides, cholesterol, and fatty acids that have been shown to best support aging skin. The triple lipid restore cream has been used in combination with energy-based procedures, to provide patients with comprehensive integrated skincare regimens. With limited clinical data and guidelines available in regenerative medicine, real-world cases serve as an invaluable guide for patients and dermatologists in navigating rejuvenation treatment plans. J Drugs Dermatol. 2024;23:9(Suppl 1):s3-14.

Photo Visualization of Skintone Compatibility of an SPF 35 Sunscreen.

BACKGROUND: Visual casts and discoloration are common barriers to sunscreen use in melanin-rich populations. However, photoprotective measures are essential for individuals with all skin types, including darker skin. METHODS: Single-center, 7-day, open-label study of healthy adult females with Fitzpatrick Skin Types (FST) IV to VI and sensitive skin treated with once-daily daily facial moisturizer sun protection factor 35 (DFM SPF35). Subjects completed a cosmetic acceptability questionnaire at days 1 and 7. Photography using VISIA CR was performed at day 7. Adverse events were monitored throughout the study. RESULTS: Thirty-two (32) subjects participated; 31.3% had FST IV, 53.1% V, and 15.6% VI skin. DFM SPF35 was viewed as cosmetically elegant. At day 1, 96.7% of subjects agreed product was easy to apply; 90.0% reported soft skin after product use; 86.7% said it had a lightweight, non-greasy feel and hydrated the skin. At day 7, 93.7% reported no visible white residue on their skin and said the product applied easily/absorbed well. The majority (90.6%) would continue using and would recommend the product; and 87.5% reported the product blended seamlessly into their skin, which agreed with clinical photography. Responses were consistent among subjects with normal, oily, or combination skin. No adverse events were reported. CONCLUSIONS: DFM SPF35 blended well into the skin and was perceived favorably among subjects with SOC after 1 and 7 days of use. Subjects felt it had good cosmetic acceptability without unacceptable white residues or a greasy feeling. Dermatologists need to be versed in products that can be used on a variety of skin types.J Drugs Dermatol. 2024;23(7):515-518.  doi:10.36849/JDD.8223.

Stability and Formulation of Erlotinib in Skin Creams.

Recent studies have highlighted the benefit of repurposing oral erlotinib (ERL) treatment in some rare skin diseases such as Olmsted syndrome. The use of a topical ERL skin treatment instead of the currently available ERL tablets may be appealing to treat skin disorders while reducing adverse systemic effects and exposure. A method to prepare 0.2% ERL cream, without resorting to a pure active pharmaceutical ingredient, was developed and the formulation was optimized to improve ERL stability over time. Erlotinib extraction from tablets was incomplete with Transcutol, whereas dimethyl sulfoxide (DMSO) allowed 100% erlotinib recovery. During preliminary studies, ERL was shown to be sensitive to oxidation and acidic pH in solution and when added to selected creams (i.e., Excipial, Nourivan Antiox, Pentravan, and Versatile). The results also showed that use of DMSO (5% v/w), neutral pH, as well as a topical agent containing antioxidant substances (Nourivan Antiox) were key factors to maintain the initial erlotinib concentration. The proposed ERL cream formulation at neutral pH contains a homogeneous amount of ERL and is stable for at least 42 days at room temperature in Nourivan cream with antioxidant properties.

Formulation development of cream with mupirocin and essential oils for eradication of biofilm mediated antimicrobial resistance.

Staphylococcus aureus (S.aureus) is both a colonizer as well as a human pathogen that causes a variety of diseases. Mupirocin is a topical antimicrobial agent which is very effective against S.aureus infection. However, treating the S.aureus infection using mupirocin could be complicated due to biofilm formation. Consequently, resistance to mupirocin occurs and leads to chronic infection. The combination of mupirocin with a compound that has biofilm eradicating effect would be an ideal solution for effectively treating biofilm infections. Therefore, in this study, we have investigated the biofilm inhibitory and eradication effect of mupirocin with three essential oils (Cinnamon Oil (CO), Eugenol (EU) and Eucalyptus Oil (EO)) against sessile S.aureus. From these preliminary results, it was found that the mupirocin-CO (0.2 µg/ml-5.218 mg/ml) combination has a better synergistic antibiofilm effect against sessile S.aureus and the fractional inhibitory concentration index was found to be 0.458. The best combination of mupirocin with CO was loaded into a non-greasy O/W cream. The physico-chemical and microbiological evaluations were carried out for the prepared cream. The prepared cream has better biofilm eradication activity (40%) when compared to a marketed cream (20%).

Clinical relevance of positive patch test reactions to lanolin: A ROAT study.

BACKGROUND: Lanolin is often included when patch testing for common contact allergens. The clinical relevance of a positive patch test reaction to lanolin markers is, however, still a subject for debate. OBJECTIVES: To evaluate Amerchol L101 as a marker of lanolin allergy and investigate the clinical impact of lanolin-containing moisturizers on healthy and damaged skin using the repeated open application test (ROAT). METHODS: Twelve test subjects and 14 controls were patch tested with Amerchol L 101 and additional lanolin markers. Subsequently, a blinded ROAT was performed on the arms of the study participants for 4 weeks. Each participant applied a lanolin-free cream base and two different lanolin-containing test creams twice daily on one arm with intact skin and on the other arm with irritant dermatitis, induced by sodium lauryl sulfate (SLS). RESULTS: Eleven test subjects (92%) had positive patch test reactions to Amerchol L 101 when retested and one test subject (8%) had a doubtful reaction. None of the study participants had any skin reactions to the ROAT on intact skin and all participants healed during the ROAT on damaged skin. CONCLUSIONS: Lanolin-containing emollients do not cause or worsen existing dermatitis when performing ROAT in volunteers patch test positive to Amerchol L101.

Agarose Stearate-Carbomer940 as Stabilizer and Rheology Modifier for Surfactant-Free Cosmetic Formulations.

Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional, high-performance polymers are good alternatives to overcome these problems. In this study, agarose stearate (AS) with emulsifying, thickening, and gel properties was synthesized. Surfactant-free cosmetic formulations were successfully prepared from AS and carbomer940 (CBM940) mixed systems. The correlation of rheological parameter with skin feeling was determined to study the usability of the mixed systems in cosmetics. Based on rheological analysis, the surfactant-free cosmetic cream (SFC) stabilized by AS-carbomer940 showed shear-thinning behavior and strongly synergistic action. The SFC exhibited a gel-like behavior and had rheological properties similar to commercial cosmetic creams. Scanning electron microscope images proved that the AS-CBM940 network played an important role in SFC's stability. Oil content could reinforce the elastic characteristics of the AS-CBM940 matrix. The SFCs showed a good appearance and sensation during and after rubbing into skin. The knowledge gained from this study may be useful for designing surfactant-free cosmetic cream with rheological properties that can be tailored for particular commercial cosmetic applications. They may also be useful for producing medicine products with highly viscous or gel-like textures, such as some ointments and wound dressings.

Analytical method development and determination of hydrocortisone acetate and fusidic acid simultaneously in cream formulation, by reversed-phase HPLC.

In this study, an accurate, simple, economical, precise and reproducible reversed-phase HPLC method was developed for the estimation of fusidic acid and hydrocortisone acetate, according to the International Conference on Harmonization guidelines, in a cream formulation. Chromatographic separation was achieved by isocratic elution, on a Shimadzu reversed-phased high-pressure liquid chromatography instrument, equipped with a C18 column (150 × 4.6 mm, 5 µm) and UV detector at 225 nm wavelength, using acetonitrile and 0.05% trifluoroacetic acid (60:40), as a mobile phase and diluent, at flow rate 2 ml/min and an injection volume of 20 µl. The calibration curves were acquired with concentration range 80-120% and mean percentage recoveries for hydrocortisone acetate and fusidic acid were 100.14 and 100.81%, respectively. The limits of detection was obtained as 6.0667 and 6.807 µm ml-1 and the limits of quantification were 20.204 and 20.628 µm ml-1 for hydrocortisone acetate and fusidic acid, respectively. All of the validation parameters were within the acceptance criteria, as per International Conference on Harmonization requirements, for hydrocortisone acetate and fusidic acid. This method was found to be validated, simple, rapid and applicable for the simultaneous estimation of hydrocortisone acetate and fusidic acid by reversed-phased high-pressure liquid chromatography, for routine analytical testing in quality control, with a run time of 8 min.

A Novel Multi-Action Emollient Plus Cream Improves Skin Barrier Function in Patients with Atopic Dermatitis: In vitro and Clinical Evidence.

BACKGROUND: Emollients capable of restoring the skin barrier function would extend their role beyond basic maintenance therapy in atopic dermatitis (AD). OBJECTIVES: Investigate the effect of a novel emollient plus cream (EC; Dermoflan®) on the skin barrier in vitro and in patients with mild-to-moderate AD. METHODS: The effect of EC on the skin barrier recovery was evaluated using a tape-stripping (TS) model. After TS, organ cultures were treated with EC (undiluted or diluted 1:1 with water) and analyzed at 18-120 h using hematoxylin and eosin, Oil Red O, immunohistochemical, and immunofluorescent techniques. In a double-blind, randomized study, EC or placebo was applied once daily for 2 months to antecubital folds of the upper and lower limbs of patients with mild-to-moderate AD in clinical remission. Epidermal thickness, vascularization, and epidermal hydration were assessed by optical coherence tomography and corneometry, respectively, at baseline, and 1 and 2 months following treatment initiation. RESULTS: Following TS, EC treatment significantly increased epidermal thickness and lipid content versus diluent in the skin organ culture, as well as claudin-1, involucrin, and caspase-14 expression, suggesting skin barrier repair. EC treatment also decreased keratin-16 expression and increased levels of Toll-like receptors 1 and 2 versus diluent, suggesting involvement in regulating the epidermal immune response. In 20 patients randomized 1:1 to EC or placebo, EC treatment at the elbow fold/popliteal fossa significantly decreased epidermal thickness after 2 months, and the number of blood vessels at the elbow fold after 1 and 2 months, versus placebo. EC significantly improved the skin hydration after 2 months versus baseline. CONCLUSIONS: This novel multi-action EC may help to restore epidermal homeostasis and improve the skin of patients with AD. Results indicate that this novel multi-action EC could be a valid adjuvant therapy in patients with AD. Key Message: Novel multi-action emollient cream helps to restore epidermal homeostasis and improves the skin affected by AD.

Effect of Rubbing Application on the Skin Permeation of Active Ingredients from Lotion and Cream.

Effect of rubbing application on the skin permeation of a hydrophilic drug caffeine (CAF) and lipophilic drug rhododendrol (RD) from lotion and cream were investigated. Skin permeation of CAF was markedly increased by rubbing action independent of the formulation type. In addition, the skin penetration-enhancement effect was affected by the rubbing direction: rubbing application against the direction of hair growth showed the highest permeation compared with rubbing applications along the direction of hair growth and in a circular pattern on the skin. On the other hand, no enhancement effect was observed by the rubbing actions on the skin permeation of RD, regardless of formulation type. Change in the infundibula orifice size of hair follicles by the rubbing and following skin stretching may be related to the higher skin permeation for CAF. In contrast, high RD distribution into the stratum corneum may be a reason why no enhancement effect was observed by the rubbing action. These results can be helpful to predict safety and effectiveness of topically applied formulations.

Aquatic Toxicity Effects and Risk Assessment of 'Form Specific' Product-Released Engineered Nanomaterials.

The study investigated the toxicity effects of 'form specific' engineered nanomaterials (ENMs) and ions released from nano-enabled products (NEPs), namely sunscreens, sanitisers, body creams and socks on Pseudokirchneriella subcapitata, Spirodela polyrhiza, and Daphnia magna. Additionally, risk estimation emanating from the exposures was undertaken. The ENMs and the ions released from the products both contributed to the effects to varying extents, with neither being a uniform principal toxicity agent across the exposures; however, the effects were either synergistic or antagonistic. D. magna and S. polyrhiza were the most sensitive and least sensitive test organisms, respectively. The most toxic effects were from ENMs and ions released from sanitisers and sunscreens, whereas body creams and sock counterparts caused negligible effects. The internalisation of the ENMs from the sunscreens could not be established; only adsorption on the biota was evident. It was established that ENMs and ions released from products pose no imminent risk to ecosystems; instead, small to significant adverse effects are expected in the worst-case exposure scenario. The study demonstrates that while ENMs from products may not be considered to pose an imminent risk, increasing nanotechnology commercialization may increase their environmental exposure and risk potential; therefore, priority exposure cases need to be examined.

Analysis of Mercury in Skin Lightening Cream by Microwave Plasma Atomic Emission Spectroscopy (MP-AES).

This research aimed at developing an analysis method, which was optimized and validated to determine the content of mercury in skin lightening cream discovered in the market in Bandar Lampung, Indonesia, through the use of microwave plasma atomic emission spectroscopy (MP-AES). The optimization on the analysis method was conducted on pump rate, viewing position, and reductant concentration in order to obtain the highest mercury emission intensity, while the solution stability was optimized to know the stability of mercury in the solution. The result showed that the method developed had precision with a relative standard deviation of 2.67%, recovery value of 92.78%, and linearity with an r value of 0.993, respectively. The sensitivity of the instrument detection had a limit of analysis method detection and quantification of 0.59 and 1.98 µg/L, respectively. The results of the test of the lightening cream (8 of 16 samples) positively contained mercury in the range of 422.61-44,960.79 ng/g. Therefore the method of analysis developed may be used for routine analysis of chemicals in any cosmetics products.

Perfume and Flavor Engineering: A Chemical Engineering Perspective.

In the last two decades, scientific methodologies for the prediction of the design, performance and classification of fragrance mixtures have been developed at the Laboratory of Separation and Reaction Engineering. This review intends to give an overview of such developments. It all started with the question: what do we smell? The Perfumery Ternary Diagram enables us to determine the dominant odor for each perfume composition. Evaporation and 1D diffusion model is analyzed based on vapor-liquid equilibrium and Fick's law for diffusion giving access to perfume performance parameters. The effect of matrix and skin is addressed and the trail of perfumes analyzed. Classification of perfumes with the perfumery radar is discussed. The methodology is extended to flavor and taste engineering. Finally, future research directions are suggested.

Aspergillus oryzae-Fermented Wheat Peptone Enhances the Potential of Proliferation and Hydration of Human Keratinocytes through Activation of p44/42 MAPK.

Identifying materials contributing to skin hydration, essential for normal skin homeostasis, has recently gained increased research interest. In this study, we investigated the potential benefits and mechanisms of action of Aspergillus oryzae-fermented wheat peptone (AFWP) on the proliferation and hydration of human skin keratinocytes, through in vitro experiments using HaCaT cell lines. The findings revealed that compared to unfermented wheat peptone, AFWP exhibited an improved amino acid composition, significantly (p < 0.05) higher DPPH scavenging capability and cell proliferation activity, and reduced lipopolysaccharide-induced NO production in RAW 264.7 cells. Furthermore, we separated AFWP into eleven fractions, each ≤2 kDa; of these, fraction 4 (AFW4) demonstrated the highest efficacy in the cell proliferation assay and was found to be the key component responsible for the cell proliferation potential and antioxidant properties of AFWP. Additionally, AFW4 increased the expression of genes encoding natural moisturizing factors, including filaggrin, transglutaminase-1, and hyaluronic acid synthase 1-3. Furthermore, AFW4 activated p44/42 MAPK, but not JNK and p38 MAPK, whereas PD98059, a p44/42 MAPK inhibitor, attenuated the beneficial effects of AFW4 on the skin, suggesting that the effects of AFW4 are mediated via p44/42 MAPK activation. Finally, in clinical studies, AFW4 treatment resulted in increased skin hydration and reduced trans-epidermal water loss compared with a placebo group. Collectively, these data provide evidence that AFW4 could be used as a potential therapeutic agent to improve skin barrier damage induced by external stresses.

Formulation of Pickering emulsions for the development of surfactant-free sunscreen creams.

OBJECTIVE: Pickering emulsions are increasingly used in the pharmaceutical and cosmetic fields, especially for topical applications, since these systems require solid particles as emulsifiers instead of surfactants which are known to cause skin irritation. The solid inorganic nanoparticles (TiO2 and ZnO) used as UV filters in sunscreen formulations may also stabilize emulsion droplets, so that the utility of surfactants may be questioned. Surfactant-free sunscreen emulsions solely stabilized by such nanoparticles (NPs) have been studied. METHODS: The ability of these NPs to stabilize o/w emulsions containing a 'model' oil phase, the C12 -C15 alkylbenzoate, has been assessed. ZnO and hydrophilic silica-coated TiO2 NPs widely used in sunscreen products were used together with their mixtures. The emulsification efficiency, the control of droplet size and the stability of o/w Pickering emulsions solely stabilized by NPs were investigated. A ZnO/TiO2 NPs mixture characterized by a theoretical SPF of 45 was finally used as unique emulsifiers to develop a surfactant-free sunscreen emulsion. RESULTS: Stable Pickering emulsions containing 10 up to 60 wt% of C12 -C15 alkyl benzoate were formulated with 2 wt% ZnO in the aqueous phase. The droplet size was controlled by the solid NPs content with respect to oil and the emulsification process. Hydrophilic TiO2 NPs did not allow the stabilization of emulsions. The substitution of TiO2 for ZnO up to 60-70 wt% in a 20/80 o/w emulsion was successfully performed. Finally, a ZnO/TiO2 NP mixture was tested as unique emulsifier system for the formulation of a sunscreen cream. Despite a lower viscosity, the obtained Pickering emulsion was stable and exhibited a photoprotective effect similar to the corresponding surfactant-based sunscreen cream with an in vitro SPF of about 45. CONCLUSION: Surfactant-free Pickering emulsions can be stabilized by the UV-filter nanoparticles for the manufacture of sunscreen products.

OBJECTIFS: Les émulsions de Pickering sont de plus en plus utilisées dans les domaines pharmaceutique et cosmétique, notamment pour les applications topiques, car ces systèmes utilisent des particules solides comme émulsifiants au lieu de tensioactifs qui sont connus pour provoquer des irritations cutanées. Les nanoparticules inorganiques solides (TiO2 et ZnO) utilisées comme filtres UV dans les formulations d'écran solaire peuvent également stabiliser les gouttelettes d'émulsion, de sorte que l'utilité des tensioactifs peut être remise en question. Des émulsions de protection solaire sans tensioactifs et uniquement stabilisées par de telles nanoparticules (NP) ont été étudiées. MÉTHODES: La capacité de ces NP à stabiliser les émulsions H/E contenant une phase huileuse «modèle¼, le benzoate d'alkyle C12 -C15 , a été évaluée. Des NP de ZnO et de TiO2 couvert de silice hydrophile, que l'on trouve largement dans les produits de protection solaire, ont été utilisées séparément et en mélange. L'efficacité d'émulsification, le contrôle de la taille des gouttelettes et la stabilité des émulsions de Pickering H/E uniquement stabilisées par les NP ont été étudiés. Un mélange de NP ZnO/TiO2 caractérisé par un SPF théorique de 45 a finalement été utilisé comme émulsifiant unique pour développer une émulsion de protection solaire sans tensioactif. RÉSULTATS: Des émulsions de Pickering stables contenant 10 à 60% en poids de benzoate d'alkyle C12 -C15 ont été formulées avec 2% en poids de ZnO dans la phase aqueuse. La taille des gouttelettes était contrôlée par la teneur en NP solides par rapport à l'huile et le procédé d'émulsification. Les NP de TiO2 hydrophile n'ont pas permis la stabilisation des émulsions. La substitution des NP de TiO2 par du ZnO jusqu'à 60-70% en poids dans une émulsion 20/80 H/E a été réalisée avec succès. Enfin, un mélange de NP ZnO/TiO2 a été testé en tant que système émulsifiant unique pour la formulation d'une crème solaire. Malgré une viscosité plus faible, l'émulsion de Pickering obtenue était stable et présentait un effet photoprotecteur similaire à la crème solaire à base de tensioactif correspondante avec un SPF in vitro d'environ 45. CONCLUSION: Les émulsions Pickering sans tensioactifs peuvent être stabilisées par les nanoparticules de filtre UV pour la formulation de produits de protection solaire.

Guinea pig seborrheic dermatitis model of Malassezia restricta and the utility of luliconazole.

Seborrheic dermatitis (SD) is a multifactorial disease in which Malassezia restricta has been proposed as the predominant pathogenic factor. However, experimental evidence supporting this hypothesis is limited. A guinea pig SD model using a clinical isolate of M. restricta was used to elucidate the pathogenicity of M. restricta. Also, the efficacy of 1% luliconazole (LLCZ) cream, a topical imidazole derivative, against M. restricta was compared with that of a 2% ketoconazole (KCZ) cream in the same guinea pig model. Dorsal skin hairs of guinea pig were clipped and treated with M. restricta by single or repeated inoculations without occlusion. Skin manifestations were examined macroscopically and histologically. A quantitative polymerase chain reaction (PCR) assay was also performed for mycological evaluation. An inflammatory response mimicking SD occurred after repeated as well as single inoculation but not in abraded skin. The inflammation score attained its maximum on day 11 and persisted until day 52. The yeast form of the fungal elements was distributed on the surface of stratum corneum and around the follicular orifices, and an epidermal and dermal histological reaction was observed. Application of 1% LLCZ or 2% KCZ cream significantly improved the skin manifestations and decreased the quantity of M. restricta rDNA in the skin lesions. The efficacy of topical antifungal drugs suggested that M. restricta is a pathogenic factor contributing to SD.

Effects of anti-wrinkle and skin-whitening fermented black ginseng on human subjects and underlying mechanism of action.

The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks FBG cream significantly reduced appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.

Scope and limitations of nuclear magnetic resonance techniques for characterisation and quantitation of vitamin D in complex mixtures.

BACKGROUND: The accurate determination of vitamin D in skin is of considerable importance in evaluating penetration of skin health products through the different layers of the skin. OBJECTIVE: We report on the characterisation and quantitation of vitamin D in an idealised sample and in complex mixtures which mimic that of a typical skin cream, using qNMR, 2D NMR and DOSY techniques. METHODS: The characterisation and quantitation conditions were acquired over several heterogeneous samples, allowing for analysis of how the dynamic range and complexity of the different sample mixtures affect the limits of detection (LOD) and limits of quantitation (LOQ) of vitamin D. NMR is of particular value to this task as it is non-destructive, uses a primary ratio method for quantification, and tolerates a wide variety of hydrophilic and hydrophobic components within a given matrix. RESULTS: In this investigation, we have attained a trueness level <10%, repeatability values of <1% and brought the limit of quantitation down to 100 nmol/L (≈limit of baseline range of vitamin D2 and D3 per litre seen in vivo), commenting on the limitations observed, such as peak overlap and sensitivity limits. CONCLUSIONS: Pure shift optimised sequences allow us to reduce peak overlapping, allowing further characterisation of individual compounds and the separation of complex mixtures using NMR.

Novel Polymeric Lotion Formulation of Once-Daily Tazarotene (0.045%) for Moderate-to-Severe Acne: Pooled Phase 3 Analysis.

Background: As current tazarotene formulations indicated for acne (0.1%) can cause irritation, a new tazarotene 0.045% lotion formu-lation was developed using polymeric emulsion technology. The objective was to assess efficacy, safety, and tolerability of tazarotene 0.045% lotion in patients with moderate-to-severe acne in a pooled analysis of data from two identical phase 3, double-blind, random-ized, vehicle-controlled 12-week clinical studies. Methods: Patients aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion applied once daily. Inflammatory and noninflammatory lesion counts and Evaluator's Global Severity Score (EGSS) were assessed. Treatment success was defined as a ≥2-grade improvement in EGSS and a score of 'clear'/'almost clear'. Adverse events (AEs) and cutaneous safety and tolerability were also assessed. Results: In total, 1614 patients (mean age: 20.5 years) were randomized to tazarotene 0.045% lotion (n=799) or vehicle (n=815). At week 12, tazarotene 0.045% lotion demonstrated statistically significant superiority versus vehicle in reducing inflammatory and non-inflammatory lesion counts (least-squares mean percent changes from baseline: inflammatory, -57.9% vs -47.8% [P<0.001]; noninflam-matory, -56.0% vs -42.0% [P<0.001]). Treatment success at week 12 was also greater with tazarotene 0.045% lotion versus vehicle (30.4% vs 17.9%; P<0.001). The most frequent treatment-emergent AEs related to tazarotene treatment were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). Conclusions: The new tazarotene 0.045% lotion formulated with polymeric emulsion technology demonstrated statistically signifi-cantly superior efficacy versus vehicle and was well tolerated in pediatric and adult patients with moderate-to-severe acne in this pooled analysis of 2 vehicle-controlled phase 3 studies. J Drugs Dermatol. 2020;19(3):272-279. doi:10.36849/JDD.2020.4869.