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Journal of Drugs in Dermatology : JDD Aug 2015Data from two Phase 3, double-blind, randomized, vehicle-controlled parallel studies were evaluated to determine the efficacy and safety of twice daily desoximetasone... (Randomized Controlled Trial)
Randomized Controlled Trial
Data from two Phase 3, double-blind, randomized, vehicle-controlled parallel studies were evaluated to determine the efficacy and safety of twice daily desoximetasone 0.25% spray for the treatment of plaque psoriasis. In addition to global disease assessments, scaling assessments were performed at baseline and at weeks 1, 2, and 4. To qualify for inclusion, subjects were required to have a clinical diagnosis of stable plaque psoriasis involving ≥10% of the body surface area (BSA), a combined target lesion severity score (TLSS) of ≥7 for the target lesion, a plaque elevation score of ≥3 (moderate) for the target lesion, and a Physician Global Assessment (PGA) score of 3 (moderate) or 4 (severe) at baseline for the overall disease severity. At the baseline visit, the mean proportions of BSA affected by psoriasis were 17% (range 10% to 86%) in the desoximetasone 0.25% spray group and 16% (range 10% to 70%) in the vehicle spray group. Approximately 90% of the patients in each group had moderate to very severe scaling at baseline. Desoximetasone 0.25% spray was effective with significant improvements in overall severity and was well tolerated, with dryness, irritation, and pruritus at the application site being the only reported adverse events occurring in >1% of patients, each of which occurred in less than 3% of patients. As a large proportion of psoriasis patients (94%) have reported being bothered by scaling, the relief of scaling was examined in these studies. At week 1, 69.7% of patients on desoximetasone 0.25% spray had scaling that was considered clear / almost clear / mild compared with 48.3% for those on vehicle spray ( P = .0027). By week 4, the proportion of patients with clear / almost clear / mild scaling had risen to 83.9% in the desoximetasone 0.25% spray group (P < .0001). After four weeks of treatment, 66.4% of patients in the topical corticosteroid group had an overall improvement of at least two grades of disease severity. This demonstrates that desoximetasone 0.25% spray provided fast and effective relief of scaling in patients with plaque psoriasis affecting 10% to 86% of their BSA.
Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Body Surface Area; Desoximetasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Psoriasis; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 26267727
DOI: No ID Found -
Cutis Nov 2006Long-term in vitro compatibility of desoximetasone and tacrolimus ointments prompted the current trial in humans. We aimed to evaluate the efficacy of twice-daily... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term in vitro compatibility of desoximetasone and tacrolimus ointments prompted the current trial in humans. We aimed to evaluate the efficacy of twice-daily simultaneous application of desoximetasone and tacrolimus in the treatment of atopic dermatitis versus tacrolimus monotherapy. Eighty-two subjects were treated in this multicenter, single-group, double-blinded, paired, 3-week follow-up clinical study of desoximetasone 0.25% and tacrolimus 0. 1% ointments versus tacrolimus 0.1% ointment and vehicle. Subjects were treated twice daily for 21 days or until clearing. Safety and efficacy were assessed at days 3, 7, 14, and 21. The combination of desoximetasone and tacrolimus ointment was superior to tacrolimus alone (P=.0002) in treating atopic dermatitis as measured by the summary of the scores for erythema, lichenification, pruritus, scaling/dryness, and oozing/crusting. Of note, pruritus at the application site was diminished in subjects treated with desoximetasone and tacrolimus together compared with tacrolimus alone (P=.04). Combination treatment with desoximetasone and tacrolimus offered increased efficacy and tolerability over tacrolimus alone in patients with atopic dermatitis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Dermatitis, Atopic; Desoximetasone; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Tacrolimus
PubMed: 17186796
DOI: No ID Found -
International Journal of Molecular... Feb 2021Psoriasis is a chronic autoimmune skin disease impacting the population globally. Pharmaceutical products developed to combat this condition commonly used in clinical...
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/cm compared to 24.22 ± 4.29 µg/cm 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.
Topics: Administration, Cutaneous; Administration, Topical; Chemical Phenomena; Chemistry, Pharmaceutical; Desoximetasone; Dose-Response Relationship, Drug; Drug Carriers; Drug Delivery Systems; Drug Stability; Gels; Humans; Hydrogen-Ion Concentration; Kinetics; Nanostructures; Permeability; Skin; Skin Absorption; Surface-Active Agents; Viscosity
PubMed: 33546426
DOI: 10.3390/ijms22041535 -
International Journal of Molecular... Oct 2023The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery...
The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery methods, such as tablets and injections. In the context of drug development, it is crucial to identify the optimal doses and delivery routes that ensure successful outcomes. Physiologically based pharmacokinetic (PBPK) models have been proposed to simulate drug delivery and optimize drug formulations, but the calibration of these models is challenging due to the multitude of variables involved and limited experimental data. One significant research gap that this article addresses is the need for more efficient and accurate methods for calibrating PBPK models for dermal drug delivery. This manuscript presents a novel approach and an integrated dermal drug delivery model to address this gap that leverages virtual in vitro release (IVRT) and permeation (IVPT) testing data to optimize mechanistic models. The proposed approach was demonstrated through a study involving Desoximetasone cream and ointment formulations, where the release kinetics and permeation profiles of Desoximetasone were determined experimentally, and a computational model was created to simulate the results. The experimental studies showed that, even though the cumulative permeation of Desoximetasone at the end of the permeation study was comparable, there was a significant difference seen in the lag time in the permeation of Desoximetasone between the cream and ointment. Additionally, there was a significant difference seen in the amount of Desoximetasone permeated through human cadaver skin at early time points when the cream and ointment were compared. The computational model was optimized and validated, suggesting that this approach has the potential to bridge the existing research gap by improving the accuracy and efficiency of drug development processes. The model results show a good fit between the experimental data and model predictions. During the model optimization process, it became evident that there was variability in both the permeability and the partition coefficient within the stratum corneum. This variability had a significant and noteworthy influence on the overall performance of the model, especially when it came to its capacity to differentiate between cream and ointment formulations. Leveraging virtual models significantly aids the comprehension of drug release and permeation, mitigating the demanding data requirements. The use of virtual IVRT and IVPT data can accelerate the calibration of PBPK models, streamline the selection of the appropriate doses, and optimize drug delivery. Moreover, this novel approach could potentially reduce the time and resources involved in drug development, thus making it more cost-effective and efficient.
Topics: Humans; Ointments; Desoximetasone; Skin; Skin Absorption; Computer Simulation; Administration, Cutaneous
PubMed: 37894801
DOI: 10.3390/ijms242015118 -
The Journal of Dermatological Treatment Feb 2018In extensive psoriasis, topical corticosteroids are generally only used to supplement phototherapy and systemic therapy. Spray formulations are easier than other vehicle... (Clinical Trial)
Clinical Trial
BACKGROUND
In extensive psoriasis, topical corticosteroids are generally only used to supplement phototherapy and systemic therapy. Spray formulations are easier than other vehicle preparations to apply and may be an option for treating extensive psoriasis.
OBJECTIVE
To evaluate the potential for hypothalamic-pituitary-adrenal axis suppression and efficacy of topical desoximetasone 0.25% spray formulation in patients with extensive psoriasis.
METHODS
A multicenter, open label, nonrandomized, clinical trial was conducted. Two groups of 12 adults with moderate to severe plaque-type psoriasis were treated with 0.25% desoximetasone spray for 28 days. Physician global assessment (PGA) and body surface area (BSA) were assessed. Cortisol-induced suppression test was performed at baseline, day 14 and day 28 to assess safety.
RESULTS
No statistically significant difference was seen in adrenal suppression; odds ratio of 0.779 (p = .85). The mean PGA improvement from baseline was 1.83 and 1.33 for moderate and severe psoriasis, respectively. Mean BSA involvement at baseline for moderate and severe psoriasis was 11% and 23%, respectively, improving to 5% and 19%, respectively.
CONCLUSIONS
Considerable improvement can be achieved with short-term potent topical corticosteroid treatment even in patients with severe, extensive psoriasis. For such use, topical desoximetasone has less risk of HPA-suppression than does topical clobetasol.
Topics: Administration, Topical; Adolescent; Adult; Aged; Body Surface Area; Dermatologic Agents; Desoximetasone; Drug Compounding; Female; Humans; Male; Middle Aged; Odds Ratio; Pituitary-Adrenal System; Psoriasis; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 28494626
DOI: 10.1080/09546634.2017.1329508 -
Pharmaceutics Jul 2023(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism...
(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.
PubMed: 37631230
DOI: 10.3390/pharmaceutics15082016 -
Journal of Drugs in Dermatology : JDD Aug 2017
BACKGROUND: Topical corticosteroids are the most common dermatologic medications and are available in numerous different vehicles. Adherence is limited by traditional... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
BACKGROUND: Topical corticosteroids are the most common dermatologic medications and are available in numerous different vehicles. Adherence is limited by traditional vehicles because they are messy and time consuming to apply. The preferred spray formulations have the advantage of being applied with ease, resulting in improved adherence and subsequently improved psoriasis. One limitation of topical treatments, especially spray vehicles, is the potential for irritation and sensitization.
OBJECTIVE: To evaluate the irritation and sensitization potential of topical desoximetasone spray formulation.
METHODS: A multicenter, double-blinded, randomized, controlled study assessed the irritancy and sensitization of 0.25% and 0.05% topical desoximetasone spray. Controls included vehicle, a positive control (0.1% sodium lauryl sulfate), negative control (0.9% saline), and an active comparator control (clobetasol spray). The primary outcome of the study was to evaluate the difference in mean cumulative irritation and potential sensitization response of desoximetasone 0.25% and 0.05% topical sprays.
RESULTS: Of the 297 enrolled, 269 completed the study per protocol for the irritation phase and 250 completed the protocol for the sensitization phase. At 22 days, desoximetasone 0.25 and 0.5% spray were less irritating than clobetasol 0.05% spray; mean irritation score difference of -0.46 and -0.57, respectively. Median total irritation score over the 22 days was 0 for all products. No subjects demonstrated any sensitization reaction to any of the six products. No serious adverse reactions were reported.
LIMITATIONS: Selection bias, use of a healthy population, limits the external validity. In addition, the duration of the study was short lived, unlike numerous inflammatory skin diseases.
CONCLUSIONS
Desoximetasone spray has little potential for irritation or sensitization. The availability of another spray option for patients desiring less messy treatment may facilitate better adherence and treatment outcomes.
J Drugs Dermatol. 2017;16(8):755-758.
.Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Dermatologic Agents; Desoximetasone; Double-Blind Method; Drug Compounding; Female; Humans; Male; Medication Adherence; Middle Aged; North Carolina; Pharmaceutical Vehicles; Treatment Outcome; Young Adult
PubMed: 28809990
DOI: No ID Found -
Turkish Journal of Pharmaceutical... Sep 2021Desoximetasone (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...
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 -based emulgel formulation to ensure enhanced skin deposition of DMS for effective treatment of plaque psoriasis.
MATERIALS AND METHODS
Different formulations (DE1-DE4) of 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/cm and 5.8±0.13 g/cm, 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 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 release kinetics revealed that the release of DMS fitted into the Korsmeyer-Peppas model.
CONCLUSION
Physicochemical characteristics and enhanced permeation of DMS from emulgel highlight its suitability to be efficiently employed for the topical treatment of skin ailments.
PubMed: 34496553
DOI: 10.4274/tjps.galenos.2020.33239 -
Journal of Drugs in Dermatology : JDD Sep 2017Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disorder. One of the most disturbing symptoms of AD is pruritus. The first line treatment for AD is... (Clinical Trial)
Clinical Trial
BACKGROUND
Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disorder. One of the most disturbing symptoms of AD is pruritus. The first line treatment for AD is topical corticosteroids, topical immunomodulators, topical barrier creams, oral antihistamines, and systemic treatments. Desoximetasone 0.25% spray is a superpotent topical corticosteroid delivered in a novel way and it may be a suitable option for the treatment of pruritus in adult atopic dermatitis patients.
STUDY DESIGN
A single-center, open labeled pilot study was conducted to investigate the efficacy and safety of desoximetasone 0.25% spray for pruritus in adult atopic dermatitis patients.
RESULTS
Twice daily application of desoximetasone 0.25% spray to affected areas resulted in a significant reduction in all outcomes (IGA, pruritus, VAS assessment of pruritus) within 1 week of initiation of treatment. The reductions exhibited were sustained throughout the study period of 4 weeks. Significant improvements in quality of life, as measured by the DLQI, were observed. No adverse events were reported.
CONCLUSION
Desoximetasone 0.25% spray is effective for treating pruritic symptoms of AD. Given its efficacy and convenience as a spray, desoximetasone 0.25% spray should continue to be evaluated as a treatment for AD in larger trials.
J Drugs Dermatol. 2017;16(9):919-922.
.Topics: Administration, Cutaneous; Adult; Dermatitis, Atopic; Dermatologic Agents; Desoximetasone; Female; Glucocorticoids; Humans; Male; Middle Aged; Pilot Projects; Pruritus; Quality of Life; Treatment Outcome
PubMed: 28915287
DOI: No ID Found