Nanostructured Non-Ionic Surfactant Carrier-Based Gel for Topical Delivery of Desoximetasone.

Psoriasis is a chronic autoimmune skin disease impacting the population globally. Pharmaceutical products developed to combat this condition commonly used in clinical settings are IV bolus or oral drug delivery routes. There are some major challenges for effectively developing new dosage forms for topical use: API physicochemical nature, the severity of the disease state, and low bioavailability present challenges for pharmaceutical product developers. For non-severe cases of psoriasis, topical drug delivery systems may be preferred or used in conjunction with oral or parenteral therapy to address local symptoms. Elastic vesicular systems, termed "niosomes", are promising drug delivery vehicles developed to achieve improved drug delivery into biological membranes. This study aimed to effectively incorporate a corticosteroid into the niosomes for improving the drug bioavailability of desoximetasone, used to treat skin conditions via topical delivery. Niosomes characterization measurements were drug content, pH, spreadability, specific gravity, content uniformity, rheology, and physicochemical properties. Formulations used a topical gelling agent, Carbomer 980 to test for in vitro skin permeation testing (IVPT) and accelerated stability studies. The developed niosomal test gel provided approximately 93.03 ± 0.23% to 101.84 ± 0.11% drug content with yield stresses ranging from 16.12 to 225.54 Pa. The permeated amount of desoximetasone from the niosomal gel after 24 h was 9.75 ± 0.44 µg/cm2 compared to 24.22 ± 4.29 µg/cm2 released from the reference gel tested. Furthermore, a drug retention study compared the test gel to a reference gel, demonstrating that the skin retained 30.88 ng/mg of desoximetasone while the reference product retained 26.01 ng/mg. A controlled drug release profile was obtained with a niosomal formulation containing desoximetasone for use in a topical gel formulation showing promise for potential use to treat skin diseases like psoriasis.

Familial Reactive Perforating Collagenosis with Adolescence-Onset: A Rare Case Report and Literature Review.

Familial Reactive Perforating Collagenosis (FRPC) is a very rare form of benign dermatosis frequently presented during early childhood and not associated with systemic diseases. Less than 50 FRPC patients have been reported in the literature. Due to the limited number of cases, the pathophysiology of this unique entity remains elusive; moreover, no standard treatment has been agreed upon. Here, we report a case of FRPC in a 20-year-old male who was presented with generalized multiple discrete papules covered with central keratotic plugs in all regions of his body, particularly in the facial area, neck, abdominal, and extensor region of the extremities for more than 7 years. Similar symptoms were acknowledged in the patient's family members. Histopathological analyses identified the crateriform shape invagination in the epidermis filled with inflammatory lymphocytes and basophilic debris and perforated by basophilic collagen bundles from the underlying dermis. Based on the clinical and histopathological findings, the patient was diagnosed with FRPC. He was treated with topical desoximetasone 0.25% cream applied 2-3 times daily. A follow-up evaluation after 4 weeks revealed a near-complete resolution of skin papules. To our knowledge, this is the first report of FRPC case from Indonesia. Unlike the majority of FRPC patients who had their disease onsets during infancy or early childhood, FRPC skin manifestations in our patient started during the adolescence period. The resolution of skin manifestations after daily application of topical desoximetasone suggests that topical corticosteroids are a potential treatment option for FRPC patients.

A Promising Approach to Treat Psoriasis: Inhibiting Cytochrome P450 3A4 Metabolism to Enhance Desoximetasone Therapy.

(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism of cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic dermatitis, and psoriasis. In this study, we aimed to investigate the anti-psoriatic effect of a low dose of desoximetasone by inhibiting cytochrome P450 3A4 metabolism in the epidermis. (2) Methods: Psoriasis-like skin was induced in BALB/c mice via the topical administration of imiquimod. The mice were then topically treated with 0.01-0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient microemulsion, 0.25% commercial desoximetasone ointment, or 0.5 mg/gm clobetasol ointment. (3) Results: The topical application of 0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation restored the imiquimod-induced skin barrier disruption and resulted in fewer severe clinical and pathological features compared with the treatments with 0.25% commercial desoximetasone ointment and 0.5 mg/gm clobetasol ointment. (4) Conclusions: The cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation improved and prolonged the therapeutic effect of cytochrome P450 3A4 substrate drugs and may be a promising approach for psoriasis treatment.

Is topical treatment effective for psoriasis in patients who failed topical treatment?

Objectives: To determine if resistance to topical treatments can be overcome under conditions promoting adherence.Materials and Methods: Twelve psoriasis patients treated with topical 0.25% desoximetasone spray were randomized to either twice daily phone call reminders or no phone call and were treated for 2 weeks. Pruritus Visual Analog Scale (VAS), Psoriasis Area and Severity Index (PASI), Total Lesion Severity Score (TLSS), and, Investigator Global Assessment (IGA) assessed disease severity.Results: Most subjects improved in most scoring parameters. 100%, 91.7%, 83.3%, and 58.3% had improvements in itching, PASI, TLSS, and IGA, respectively.Conclusions: While our sample size was small and treatment duration short, the effect size of topical treatment was large under conditions designed to promote adherence.

Development of an Aloe vera-based Emulgel for the Topical Delivery of Desoximetasone

Objectives: Desoximetasone (DMS) is a widely recommended drug for the topical treatment of plaque psoriasis. However, low water solubility and short half life of DMS present major obstacles in the development of an effective topical formulation. Thus, there is a demand for the development of a safe and effective topical system to deliver hydrophobic DMS. The present study aimed to develop an Aloe vera-based emulgel formulation to ensure enhanced skin deposition of DMS for effective treatment of plaque psoriasis. Materials and Methods: Different formulations (DE1-DE4) of Aloe vera emulgel were prepared using dispersion technique, wherein varying concentrations of propylene glycol (6-14% w/w) and carbopol 934 (0.5-1.0% w/w) were used. Results: Zetasizer measurements revealed that the globule size of the formulations ranged from 10.34 µm±0.9 to 14.60 µm±1.4 (n=50). Extrudability analysis for the DE3 and DE2 formulations revealed an extrudability of 5.6±0.11 g/cm2 and 5.8±0.13 g/cm2, respectively. The pH of the formulations was recorded in the range of 5.8-6.8. Among these formulations, DE3 showed a maximum drug content of 94.64%±0.29 (n=3), and thus was used for further in vitro evalutions. A texture analyzer showed that an optimized DE3 formulation was firmer and exhibited optimal spreadability in comparison with the DE2 formulation. For DE3, the mean max force that represented "firmness" was recorded to be 833.37 g, where as the mean area, denoting "work of shear", was 324.230 g.sec. The DE3 formulation exhibited DMS permeation of 95.40±1.6% over a period of 7 h, as detrmined using an in house fabricated Franze diffusion cell. Evaluation of in vitro release kinetics revealed that the release of DMS fitted into the Korsmeyer-Peppas model. Conclusion: Physicochemical characteristics and enhanced in vitro permeation of DMS from Aloe vera emulgel highlight its suitability to be efficiently employed for the topical treatment of skin ailments.

Patients preferences for different corticosteroid vehicles are highly variable.

Introduction: Topical corticosteroids, available in an array of vehicles are used to control a variety of inflammatory skin diseases. Patients preferences for different vehicles may affect their willingness to use treatment. We assess corticosteroid vehicle preference and potential impact of topical characteristics on adherence and quality of life in patients with psoriasis.Methods: Subjects with psoriasis were recruited from Wake Forest University Dermatology Clinic. Subjects sampled desoximetasone 0.25% spray, betamethasone valerate 0.1% cream, triamcinolone acetonide 0.1% ointment, fluocinonide 0.05% gel, betamethasone valerate 0.1% lotion, clobetasol propionate 0.05% foam, and fluocinonide 0.05% solution in a predetermined randomized order. Subjects completed a Vehicle Preference Measure, Determinants of Adherence Measure, and a Determinants of Quality of Life Measure.Results: Patients preferences for the various products were highly variable. Regarding Determinants of Adherence, patients perception of absorption of the medication was ranked as 'quite important/extremely important' by 85% of total subjects. A majority of patients rated medication side effects as 'quite important/extremely important' when asked to consider topical characteristics effect on quality of life.Discussion: There was wide variation in patient preference for topical medication vehicles used for treating psoriasis. Several vehicle characteristics were considered important to adherence. Given the marked variation in vehicle preference, topical treatment should be individualized according to patients preferences.

Evaluations of Quality by Design (QbD) Elements Impact for Developing Niosomes as a Promising Topical Drug Delivery Platform.

Topical corticosteroids are used to treat a variety of skin conditions such as allergic reactions, eczema, and psoriasis. Niosomes are a novel surfactant-based delivery system that may be used to deliver desoximetasone via topical product application in order to mitigate common side effects associated with traditional oral delivery routes. The aim of this research was to identify the critical material attributes (CMAs) and critical process parameters (CPPs) that impact key characteristics of drug-loaded niosomes using a systematic quality by design (QbD) approach. An organic phase injection method was developed and used to manufacture the niosomes. The CMAs were identified to be drug amount, concentrations of surfactant and cholesterol, and types of lipids. The CPPs were phase volumes, temperature, mixing parameters, and addition rate based on previous research. The quality attributes measured were entrapment efficiency, particle size distribution, PDI, and zeta potential. These were used to determine the quality target product profile (QTPP) of niosomes. The experimental data indicate that the critical impacting variables for niosomes are: surfactant and cholesterol concentrations, mixing parameters, and organic-phase addition rate. Based on the experimental results of this study methanol:diethyl ether (75:25) as the organic system, drug:surfactant:cholesterol in 1:2:1 concentration, stearic acid as the charge-inducing material, 20 mL external phase and 10 mL internal phase volume, 65 °C external phase temperature, 60 min mixing time, 650 RPM mixing speed and 1 mL/ml addition rate is the ideal combination to achieve desirable desoximetasone niosomes with optimum entrapment efficiency and particle size for topical application.

Six week evaluation of the potential for topical desoximetasone 0.25% spray to induce photoallergic skin reaction.

PURPOSE: Desoximetasone 0.25% topical spray is a novel formulation that has not been tested or approved for safety and efficacy. The primary objective was to determine the potential of desoximetasone 0.25 and 0.05% topical sprays, as well as a vehicle to induce photoallergic skin reaction after repeated topical application and irradiation to the skin using a controlled photopatch testing procedure. MATERIALS AND METHODS: 53 subjects completed the study, each with six application sites (two of each treatment), three of which were irradiated and three non-irradiated, for an induction period of three weeks and then challenge period at week 6. RESULTS: Desoximetasone 0.25 and 0.05%, as well as vehicle showed no evidence of potential to induce photosensitization. There was statistically significantly greater irritation at the vehicle irradiated site in comparison to the irradiated treatment area of desoximetasone 0.25% (p = .005) and the irradiated treatment area of desoximetasone 0.05% (p = .008). CONCLUSION: Our results suggest that regular treatment with desoximetasone 0.25 and 0.05% spray, followed by UV light exposure does not induce photosensitization or photo-irritation. These findings increase confidence for the use of this topical spray in eczema or psoriasis patients who may also be receiving UV light therapy and may contribute to the clinical management of these patients.

4-Day evaluation of the irritation potential of topical desoximetasone 0.25% and 0.05% spray on light-exposed skin.

PURPOSE: The safety and potential side effects of desoximetasone 0.25% and 0.05% sprays have not previously been studied. The primary objective of this study was to determine the irritation potential of desoximetasone 0.25%, 0.05% and vehicle sprays in response to irradiation. MATERIALS AND METHODS: Thirty-four subjects were enrolled in the study, each with three study treatments (desoximetasone 0.25%, 0.05% topical sprays and vehicle) were applied to two sites each on the back of every subject, with half of the sites irradiated with filtered UV light. Dermal reactions at the test sites were evaluated using a visual scale with corresponding numerical scores that rated the degree of erythema and oedema. RESULTS: Desoximetasone 0.25%, 0.05%, and vehicle caused no detectable signs of phototoxicity when examined on days 3 and 4. Mean scores of desoximetasone 0.25%, 0.05% and vehicle to non-irradiated treatment areas showed no signs of irritation. CONCLUSIONS: Our results suggest that regular application of desoximetasone 0.25% and 0.05% topical sprays do not induce photosensitization or photoirritation. The safety of this topical spray may help with clinical management of patients using topical corticosteroids while also receiving therapeutic UV light exposure. Thus, patients can use desoximetasone sprays without concerns of side effects due to therapeutic light or sun exposure.

An Open-label, Observational Study Evaluating Desoximetasone Topical Spray 0.25% in Patients with Scalp Psoriasis.

Objective: The goal of this study was to evaluate efficacy and safety of desoximetasone spray 0.25%, a topical corticosteroid, in the management of scalp and body psoriasis. Design: This was an open-label, observational study. Participants: Twenty adults aged 18 years or older with chronic scalp psoriasis present on at least 30 percent of the scalp surface area and an Investigator Global Assessment (IGA) scale score of scalp disease of at least 2 on a scale of 0 to 4 were included in the study. Measurements: Study spray was applied twice daily for four weeks, followed by 12 weeks of twice-daily application for two consecutive days weekly. Results: At Week 4, the mean Physician Global Assessment (PGA) scale score had decreased 54.8 percent, from moderate disease to almost clear. Body surface area (BSA) had decreased by 51.2 percent, BSA × PGA had decreased by 63 percent, and scalp IGA had decreased by 64.5 percent from moderate to almost clear. Additionally, mean Psoriasis Scalp Severity Index (PSSI) score was 27.3±10.0 at baseline and decreased 82.4 percent to 4.8±5.2 and scalp surface area (SSA) was reduced by 70.7 percent at Week 4. The initial Scalp Index score was a mean of 65.7±15.0 at baseline and was reduced by 44.3 percent and 40.8 percent at Weeks 4 and 16, respectively. The initial response was maintained after a change to twice-weekly, twice-daily dosing, with a 48.4-percent decrease in PGA, a 17.1-percent decrease in BSA, a 31.5-percent decrease in BSA × PGA, a 51.6-percent decrease in scalp IGA, a 63.4 percent decrease in PSSI, and a 42.3-percent decrease in SSA seen at Week 16. Minimal adverse events were experienced by seven subjects. Conclusion: Desoximetasone spray 0.25% produced rapid improvements in PGA, BSA, BSA×PGA, scalp IGA, PSSI, SSA.