755-nm picosecond laser plus topical 20% azelaic acid compared to topical 20% azelaic acid alone for the treatment of melasma: a randomized, split-face and controlled trial.

PURPOSE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients. METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient's satisfaction assessments (PSA). RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period. CONCLUSION: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).

Application and evaluation of topical amphotericin B for the treatment of respiratory fungal infections.

BACKGROUND: In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections. METHODS: We conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023. RESULTS: Data from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects. CONCLUSION: The combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.

QbD Based Formulation Development and Optimisation of Ozenoxacin Topical Nano-Emulgel and Efficacy Evaluation Using Impetigo Mice Model.

To formulate and optimize Ozenoxacin nano-emulsion using Quality by Design (QbD) concept by means of Box-Behnken Design (BBD) and converting it to a gel to form Ozenoxacin nano-emulgel followed by physico-chemical, in-vitro, ex-vivo and in-vivo evaluation. This study demonstrates the application of QbD methodology for the development and optimization of an effective topical nanoemulgel formulation for the treatment of Impetigo focusing on the selection of appropriate excipients, optimization of formulation and process variables, and characterization of critical quality attributes. BBD was used to study the effect of "% of oil, % of Smix and homogenization speed" on critical quality attributes "globule size and % entrapment efficiency" for the optimisation of Ozenoxacin Nano-emulsion. Ozenoxacin loaded nano-emulgel was characterized for "description, identification, pH, specific gravity, amplitude sweep, viscosity, assay, organic impurities, antimicrobial effectiveness testing, in-vitro release testing, ex-vivo permeation testing, skin retention and in-vivo anti-bacterial activity". In-vitro release and ex-vivo permeation, skin retention and in-vivo anti-bacterial activity were found to be significantly (p < 0.01) higher for the nano-emulgel formulation compared to the innovator formulation (OZANEX™). Antimicrobial effectiveness testing was performed and found that even at 70% label claim of benzoic acid is effective to inhibit microbial growth in the drug product. The systematic application of QbD principles facilitated the successful development and optimization of a Ozenoxacin Nano-Emulsion. Optimised Ozenoxacin Nano-Emulgel can be considered as an effective alternative and found to be stable at least for 6 months at 40 °C / 75% RH and 30 °C / 75% RH.

Compatibility of Caffeine Clobetasol Propionate Dutasteride Nicotinamide and Progesterone in TrichoFoam™, a Natural Vehicle for Hair Foams.

BACKGROUND: Alopecia is a chronic dermatological disorder affecting men and women worldwide. Given the high incidence and significant impact on patients' well-being, options for managing and treating alopecia are essential. Topical available options remain limited and oral products may result in adverse effects. TrichoFoam™ is a ready-to-use foaming vehicle developed for compounding pharmacies and formulated with gentle, non-irritating, and sensory-pleasant ingredients. OBJECTIVE: The purpose of this study was to assess topical foams' physicochemical and microbiological stabilities of formulations compounded with TrichoFoam™ as the ready-touse vehicle. METHODS: HPLC analyses were conducted in a bracketed study covering concentrations of 0.1% to 2.0% of caffeine, 0.01% to 0.1% of clobetasol propionate, 0.1% to 0.25% of dutasteride, 0.25% to 0.50% of nicotinamide, and 0.25% to 2.5% of progesterone compounded with TrichoFoam™. Antimicrobial Effectiveness Testing was conducted at the beginning and end of the studies. RESULTS: Most formulations presented a beyond-use date of at least 90-180 days, except for clobetasol propionate, which showed compatibility for 14 days, and dutasteride 0.25%, which showed a BUD of 30 days. CONCLUSION: This validates the stability of the active pharmaceutical ingredients from different pharmacological classes with TrichoFoam™, suggesting that this ready-to-use vehicle can be an excellent alternative for personalized alopecia treatment.

PHARMACOKINETICS AND EFFICACY OF A SINGLE TOPICAL DOSE OF EPRINOMECTIN IN GIRAFFE (GIRAFFA SPP.).

Growing resistance to current antiparasitic medications, both in livestock and in zoological species under human care, makes it imperative to evaluate available drugs on the market, such as eprinomectin. In this prospective study, five males and one female of reticulated (Giraffa reticulata; n = 2), Masai (Giraffa tippelskirchii; n = 1), Nubian (Giraffa camelopardalis; n = 2), and hybrid subspecies (n = 1) of giraffe, received 1.5 mg/kg eprinomectin topically along the dorsum. Using high-performance liquid chromatography, concentrations of eprinomectin in plasma samples collected at 0, 4, 24, and 48 h, and 7, 14, 21, and 28 d were evaluated following drug administration. Complete blood cell counts and biochemistry panels were performed before (n = 6) and after (n = 3) eprinomectin administration. Samples for modified double centrifugal fecal flotation (n = 6) were evaluated prior to eprinomectin administration to evaluate for endoparasites and were repeated after the study (n = 5). Noncompartmental pharmacokinetic analysis was applied to the data. The observed maximum plasma concentration was 11.45 ng/ml and the time of observed maximum concentration was 2.67 d. The mean terminal half-life was 5.16 d. No adverse effects were observed related to eprinomectin administration and no blood work changes were observed. Parasite loads decreased (n = 3) or did not change (n = 2) after eprinomectin administration. The mean peak plasma concentration of eprinomectin in giraffe was similar to that achieved in cattle, despite using three times the dose.

Expert Recommendations on Use of Topical Therapeutics for Vitiligo in Pediatric, Adolescent, and Young Adult Patients.

Importance: Evidence-based recommendations for the treatment of vitiligo in pediatric, adolescent, and young adult patients in the US are needed. Objective: To develop evidence- and consensus-based expert recommendations on the diagnosis and treatment of vitiligo in young patients. Evidence Review: A process was developed to produce consensus recommendations addressing questions regarding pediatric vitiligo. A librarian-conducted literature review was performed using articles that met the inclusion criteria: published in English, containing primary data (including meta-analysis) and pediatric-specific data, and analysis of 6 or more patients. Included articles were graded by the Strength of Recommendation Taxonomy criteria and Oxford Centre for Evidence-based Medicine's Levels of Evidence and Grades of Recommendation. Research questions were reviewed on May 9, 2022, through a video conference. One month after the conference, participants participated in an online survey documenting their level of agreement with the generated statements, using a 5-point Likert scale. Findings: Articles on topical corticosteroids and/or topical calcineurin inhibitors (n = 50), topical Janus kinase inhibitors (n = 5), pseudocatalase (n = 2), and microdermabrasion (n = 2) met inclusion criteria. Forty-two recommendations were made on the diagnosis of vitiligo and optimal topical therapeutics, with 33 recommendations obtaining a 70% or greater composite agreement and strong agreement. Topical calcineurin inhibitors twice daily, topical corticosteroids with time limitation due to atrophy risk, and topical ruxolitinib, 1.5%, cream-used off-label for patients younger than 12 years and limited to nonsegmental vitiligo-were identified as evidence-based first-line therapies in the management of pediatric and adolescent patients, with specific guidance on age-based data, minimum therapeutic trial of 6 months or greater, prolonged therapy to prevent recurrence, and the positive benefit of coordinated use of UV therapeutic sources. Conclusions and Relevance: Evidence supports the use of topical calcineurin inhibitors, topical corticosteroids, and topical Janus kinase inhibitors as effective therapeutics for vitiligo in pediatric, adolescent, and young adult patients, with specific decisions on choice of agent based on factors such as site location, body surface area, and age.

Topical steroids or emollients: does order matter?

Topical corticosteroids, topical steroid-sparing agents, and emollients are all used to treat atopic dermatitis. However, there are no formal guidelines dictating the order and timing in which these topical modalities should be applied. Additionally, the order of application may change drug absorption, efficacy, and distribution. This is especially important for patients with atopic dermatitis. These patients have a dysfunctional skin barrier, which can lead to greater systemic absorption of drugs. Moreover, children already have an increased rate of systemic absorption due to a higher ratio of body surface area to body weight. Thus, the order of application of topical regimens is of the utmost importance in pediatric dermatology. This manuscript presents an updated review of the literature with a focus on guiding clinicians toward the best practices from the available resources.

Characteristics of atopic dermatitis patients using complementary and alternative medicine: A literature review.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Due to the burden of the disease, some patients try complementary and alternative medicine (CAM). OBJECTIVE: To identify characteristics associated with CAM use in children and adults with AD. METHODS: We conducted a literature review in accordance with the PRISMA international guidelines for literature reviews and meta-analyses. A systematic search was performed in the PubMed database. Qualitative and quantitative analyses using a χ2 test were performed to compare characteristics between CAM users and non-users. A p-value of <0.05 was considered statistically significant. RESULTS: Out of 514 articles retrieved, 12 studies were included, giving a total of 2240 patients. Our statistical analysis identified an association between CAM use and rhino-conjunctivitis (p = 0.015 in children, p = 0.041 in adults), topical corticosteroid use (p = 0.042 in children, p = 0.008 in adults), and daily application of moisturizing cream (p = 0.002 in children, p < 0.001 in adults). Gender did not affect the decision to use CAM (p > 0.05). In studies, a higher number of affected eczema sites (p < 0.001), prior use of more than two conventional treatments (p = 0.047), and food avoidance diets (p = 0.016) were predictive of CAM use in children. In adults, a younger age (p < 0.05), higher education level (p = 0.043), and lower age at AD onset (p = 0.004) were related to CAM use. DISCUSSION: To our knowledge, this is the first literature review focusing on socio-demographic and disease determinants related to CAM use among AD patients. The lack of homogeneity in measuring tools makes it difficult to compare and synthesize the studies.

Treatment of Refractory Vulvar Lichen Sclerosus With Methotrexate.

We report the successful treatment of severe vulvar lichen sclerosus refractory to topical corticosteroids in 3 adult female patients using low-dose oral methotrexate. All cases reported symptomatic and clinical improvement within 12 weeks.

Drug-like properties of tyrosine kinase inhibitors in ophthalmology: Formulation and topical availability.

Tyrosine kinase inhibitors (TKIs) can inhibit edema and neovascularization, such as in age-related macular degeneration and diabetic retinopathy. However, their topical administration in ophthalmology is limited by their toxicity and poor aqueous solubility. There are multiple types of TKIs, and each TKI has an affinity to more than one type of receptor. Studies have shown that ocular toxicity can be addressed by selecting TKIs that have a high affinity for specific vascular endothelial growth factor receptors (VEGFRs) but a low affinity for epidermal growth factor receptors (EGFRs). Drugs permeate from the aqueous tear fluid into the eye via passive diffusion. Thus, a sustained high concentration of the dissolved drug in the aqueous tear fluid is essential for a successful delivery to posterior tissues such as the retina. Unfortunately, the aqueous solubility of the TKIs that have the most favorable VEGFR/EGFR affinity ratio, that is, axitinib and cabozantinib, is well below 1 µg/mL, making their topical delivery very challenging. This is a review of the drug-like properties of TKIs that are currently being evaluated or have been evaluated as ophthalmic drugs. These properties include their solubilization, cyclodextrin complexation, and ability to permeate from the aqueous tear fluid to the posterior eye segment.

Topical Use of Low-dose Tranexamic Acid Has no Effect on Drainage Volume after Medial Open Wedge High Tibial Osteotomy: A Case Control Study.

OBJECTIVE: Many studies reported that tranexamic acid (TXA) was effective in reducing surgical blood loss in the perioperative period of medial open wedge high tibial osteotomy (MOWHTO). However, few studies focused on the simple topical use of TXA in MOWHTO, and the modality and dosage of topical use of TXA varied. The purpose of this study was to observe the effect of topical use of low-dose TXA on drainage volume after MOWHTO, and to analyze the related influencing factors. METHODS: Data of patients who underwent MOWHTO combined with arthroscopic knee surgery in our department from January 2019 to September 2021 were retrospectively analyzed. A total of 105 patients (38 males and 67 females, aged 57.7 ± 7.5 years) were included in this study who received topical TXA or no TXA. The patients were divided into three groups: control group (39 cases), 0.5 g TXA group (40 cases), 1 g TXA group (26 cases). Postoperative drainage volume, wound healing, incidence of hematoma and deep venous thrombosis (DVT) were observed and analyzed in the three groups. The effects of gender, hypertension and diabetes on postoperative drainage volume were analyzed using a t-test. The correlation between age, body mass index (BMI), osteotomy gap and postoperative drainage volume were analyzed using the Pearson correlation coefficient. RESULTS: The average postoperative drainage volume of the control group was 259.54 ± 226.33 mL, that of the 0.5 g TXA group was 277.18 ± 177.68 mL, and that of the 1 g TXA group was 229.15 ± 219.93 mL. There was no statistically significant difference in postoperative drainage volume among the three groups (F = 0.423, p = 0.656). There was no local hematoma and wound infection in the three groups. The wound fat liquefaction was found in one patient of the control group. The incidence of DVT was 38.9% (7/18) and 57.1% (8/14) in the control group and 0.5 TXA group, respectively. There was no significant difference in the incidence of DVT between the above two groups (p = 0.476). The average postoperative drainage volume of male patients in the three groups was higher than that of female patients, and the differences were statistically significant (p < 0.05). There was no correlation between age, BMI, osteotomy gap and postoperative drainage volume in the three groups (p > 0.05). CONCLUSION: Topical use of low-dose TXA has no significant effect on drainage volume after MOWHTO. The drainage volume after MOWHTO in male patients was more than that in female patients. Topical administration of low-dose TXA does not increase postoperative complications, such as DVT and hematoma.

Efficacy of diltiazem 2% rectal gel in the treatment of chronic anal fissure: a retrospective observational study.

OBJECTIVE: The aim of this study is to describe the effectiveness and safety of a magistral formulation of diltiazem 2% rectal gel as a treatment for chronic anal fissure. MATERIAL AND METHODS: A retrospective observational study of all patients that began treatment with diltiazem 2% gel during 2019. The primary endpoint of the study was anal fissure healing. We also looked for differences in effectiveness between those initiating treatment and those who had been previously treated, long-term effectiveness through a 2-year follow-up and frequency of adverse effects. RESULTS: Of the 166 patients included in the study, anal fissure healed in 72.9%. We detected adverse effects in 12 patients, the most common was local irritation. After 2 years of follow-up, 88% of patients did not relapse. CONCLUSION: In this study, use of topical diltiazem 2% has been shown to be effective and safe in the treatment of anal fissure and should be considered as the first line of therapy.

OBJETIVO: El objetivo de este estudio es describir la efectividad y la seguridad de una fórmula magistral de diltiazem 2% gel rectal, como tratamiento de la fisura anal crónica. MATERIAL Y MÉTODOS: Un studio observacional retrospectivo de todos los pacientes que comenzaron a ser tratados con diltiazem 2% gel durante el año 2019. La variable principal del estudio fue la cicatrización de la fisura anal. También se buscaron diferencias de efectividad entre aquellos que iniciaban el tratamiento y los que ya habían sido tratados previamente, efectividad a largo plazo mediante un seguimiento de 2 años y frecuencia de aparición de efectos adversos. RESULTADOS: De los 166 pacientes incluidos en el estudio, el 72,9% cicatrizaron la fisura anal. No detectamos diferencias estadísticamente significativas de efectividad entre los pacientes naive y aquellos que ya habían sido tratados. Detectamos efectos adversos en 12 pacientes, siendo el más frecuente la irritación local. Tras 2 años de seguimiento, el 88% de los pacientes no presentaron ninguna recaída. CONCLUSIÓN: En este estudio, el uso de diltiazem 2% tópico ha mostrado ser efectivo y seguro en el tratamiento de la fisura anal y debería considerarse como primera línea terapéutica.

A proposal to reduce the amount of permethrin entering wastewater resultant from topical use to treat scabies.

The incidence of scabies is rising in the last years. Subsequently, the use of pharmaceuticals to treat the disease has also increased. Treatment with topical permethrin is usually recommended as a first line agent. This substance is also an aquatic contaminant that is toxic for many non-target organisms, and has been included as a priority substance in the recently published proposal of the European Water Framework Directive. Current guidelines neglect the potential environmental impact of this drug, recommending that the cream should be applied head to toe and "washed off after 8-12 h". Recently, a wiping procedure before hand washing after application of the topical treatment resulted in a 66 % reduction of the amount of diclofenac released in wastewater. The authors suggested that this method could be explored for other topical treatments. In the case of scabiosis, a protocol implicating the whole body needs to be designed. The absorption of topical permethrin is low. Considering the growing incidence of scabies, the amount of the pyrethroid reaching the environment may also be increasing. Therefore, we believe that applying the wiping procedure to the case of topical permethrin deserves consideration. Other measures to minimize the amount of permethrin residues reaching wastewater by washing clothes and bed linen such as wearing single-use pijamas should also be explored. In conclusion, we need to apply a One Health approach in the treatment with scabies, without neglecting the environmental impact of pharmaceuticals. It is not rational to forget drugs once they go down the drain.

Clinical Evaluation of a Topical Unani Polyherbal Formulation in the Management of Photodamaged Facial skin: An open-label Standard Controlled Trial.

Introduction: Ageing is a natural process of life. With increasing age, the skin suffers progressive morphological and physiological decrement. Hyperpigmentation, Wrinkles, and roughness of skin are some of the symptoms of aged skin. Exposure to sunlight, pollution, stress, nicotine, etc aggravates Skin aging. This study aimed to determine the efficacy and safety of polyherbal formulation and compare its efficacy with the standard drug tretinoin in subjects of moderate to advanced Photoaged facial skin. Ingredients of polyherbal formulation are Aarade baqla (Vicia faba), Jau (Hordeum vulgare), Nakhud (Cicer arietinum),Masoor (Lens esculenta), Tukhm e turb (Raphanus sativus), Khardal (Brassica nigra), Haldi (Curcuma longa), Kateera (Cochlospermum religiosum). Methods: This was a randomized open-label standard controlled study. 82 eligible subjects were allocated equally into test and control groups by computer-generated random numbers. In the test group, a paste of 15 gm polyherbal formulation in milk, and the control group, 0.025% Tretinoin 1 gram was used topically on the face once a day for two months. The response was assessed by theclinician using following different scales for different parameters. Assessment of Skin hyperpigmentation: It was assessed by the Skin Hyperpigmentation Index online calculator (SHI). It describes the ratio of two scores, namely the hyperpigmented skin of the affected area and normal sun-protected skin from the same patient. The image was recorded with a Digital microscope-Win7 from a hyperpigmented area and normal sun-protected area. Both the images were uploaded on https://shi.skinimageanalysis.com/ and calculated the mean value of hyperpigmentation. SHI ranges from 1 (no hyperpigmentation) to 4 (maximum hyperpigmentation) where scores between 1 and 2 showed as light hyperpigmentation, 2-3 as medium hyperpigmentation, and scores between 3 and 4 as severe hyperpigmentation. Assessment of Fine wrinkles: Fine wrinkles number was determined by digital photography. The photographs were taken through Canon EOS 1500D DSLR Camera with an 18-55 mm Lens. Three images were taken of each subject's face (right, left, and center full face) on Baseline and Day 15th, 30th, 45th, and 60th to assess visible changes/improvement in their fine wrinkles score. Assessment of Nasolabial Fold: Modified Fitzpatrick Wrinkle Scale (MFWS) was used to assess Nasolabial folds. The scale comprised four main classes of Nasolabial wrinkling: 0, 1, 2, and 3 representing absent, fine, moderate, and deep wrinkles, respectively, and three inter classes i.e., 0.5, 1.5, and 2.5 to estimate wrinkle depth. The definitions of the entire classes of the scale are as follows: Class 0 = No wrinkle. No visible wrinkle; continuous skin line; Class 0.5 = Very shallow yet visible wrinkle; Class 1= Fine wrinkle. Visible wrinkle and slight indentation; Class 1.5= Visible wrinkle and clear indentation. <1-mm wrinkle depth; Class 2= Moderate wrinkle. Visible wrinkle, 1- to 2-mm wrinkle depth; Class 2.5= Prominent and visible wrinkle. More than 2-mm and less than 3-mm wrinkle depth; Class 3=Deep wrinkle. Deep and furrow wrinkle; more than 3-mm wrinkle depth. Assessment of Forehead lines score: Forehead lines were assessed (number and depth) by a Validated Grading Scale for Forehead Lines. The Forehead Lines Grading Scale is a 5- point photonumeric rating scale that was developed to objectively quantify resting (static) and hyperkinetic (dynamic) forehead lines. The scale ratings are 0 for no wrinkles, 1 for no wrinkles present at rest but fine lines with facial expression, 2 for fine wrinkles present at rest and deep lines with facial expression, 3 for fine wrinkles present at rest and deeper lines with facial expression, and 4 for deeper wrinkles at rest and deeper furrows with facial expression. Assessment of lateral canthal lines: The number of lateral canthal lines was determined by a Validated Grading Scale for Crow's Feet. The Crow's Feet Grading Scale is a 5- point photonumeric rating scale developed to objectively quantify the severity of crow's feet. This scale was applied to two separate evaluations of crow's feet: at rest (static) and with expression (dynamic). The scale ratings are 0 for no wrinkles, 1 for very fine wrinkles, 2 for fine wrinkles, 3 for moderate wrinkles, and 4 for severe wrinkles. Assessment of Facial Skin Roughness: The Allergan Skin Roughness Scale was used for facial skin roughness assessment. The area of assessment for the Allergan Skin roughness Scale is the area between the nasolabial fold to the preauricular cheek and from the inferior orbital rim to the mandible. The Allergan Skin Roughness Scale assigns a grade from none (0) to extreme (4) that describes the severity of skin coarseness, crosshatching, and elastosis in the midface area. The scale grading are 0 (None) Smooth visual skin texture, 1 (Minimal) Slightly coarse and uneven visual skin texture, 2 (Moderate) Moderately coarse and uneven visual skin texture; may have early elastosis, 3 (Severe) Severely coarse visual skin texture, cross-hatched fine lines; may have some elastosis, and 4 (Extreme) Extremely coarse visual skin texture, cross Hatched deep creases; extreme elastosis. Assessment of Facial Dullness: Dullness was assessed on a clinical basis with an arbitrary scoring ranging from 0 to 9 where 0-3=mild, 3.5-6=moderate, and 6.5-9=severe facial skin dullness. Assessment of quality of life: Subjects' life quality was assessed by the Dermatology Life Quality Index questionnaire. It consists of 10 questions. Each question is scored on a four-point Likert scale: Very much = 3, A lot = 2, A little = 1, Not at all = 0, Not relevant = 0 and Question unanswered = 0. The DLQI is calculated by adding the score of each question, resulting in a maximum of 30 and a minimum of 0. Where, 0-1= no effect at all on patient's life, 2-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life. Results: Both groups showed a significant improvement in Fine Wrinkles, Forehead Lines, Crow's Feet, Roughness, Dullness, Nasolabial Fold, Hyperpigmentation, and Quality of Life parameters. (P < .001) A large number of subjects in the control group reported mild to moderate redness, itching, dryness, and blackening of the skin, while in the test group, absolutely no side effects were reported during treatment. Conclusion: The effects in both groups were substantial, but the polyherbal formulation is safe and effective for use in photoaged facial skin. It may be a more feasible easily accessible cheap and safe formulation to prevent skin aging and restore skin elasticity and make skin brighter. Further studies to evaluate the efficacy of formulation on objective parameters using standard instruments should be done for appropriate measurements of parameters.

Pharmacokinetic Profile of Brepocitinib with Topical Administration in Atopic Dermatitis and Psoriasis Populations: Strategy to Inform Clinical Trial Design in Adult and Pediatric Populations.

INTRODUCTION: Topical brepocitinib, a tyrosine kinase (TYK)2/Janus kinase (JAK)1 inhibitor, is in development for psoriasis (PsO) and atopic dermatitis (AD). Quantitative analyses of prior clinical trial data were used to inform future clinical trial designs. METHODS: Two phase 2b studies in patients with AD and PsO were used to characterize the amount of topical brepocitinib and the resultant systemic trough concentration (CTrough) using a linear mixed-effects regression (LMER). This model was used to predict brepocitinib systemic CTrough for higher treated body surface areas (BSAs) in adults and children. Information from non-clinical and clinical trials with oral brepocitinib was leveraged to set safety thresholds. This combined approach was used to inform future dose-strength selection and treated BSA limits. RESULTS: Data from 256 patients were analyzed. Patient type, dose strength, and frequency had significant impacts on the dose-exposure relationship. Systemic concentration in patients with PsO was predicted to be 45% lower than in patients with AD from the same dose. When topically applied to the same percentage BSA, brepocitinib systemic exposures are expected to be comparable between adults and children. The systemic steady-state exposure after 3% once daily and twice daily (2 mg/cm2) cream applied to less than 50% BSA in patients with AD and PsO, respectively, maintains at least a threefold margin to non-clinical safety findings and clinical hematologic markers. CONCLUSION: The relationship between the amount of active drug applied and brepocitinib systemic CTrough, described by LMER, may inform the development strategy for dose optimization in the brepocitinib topical program.