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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 -
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 -
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 -
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 -
The Journal of Dermatological Treatment Jun 2018The 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... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Administration, Topical; Adult; Dermatologic Agents; Desoximetasone; Double-Blind Method; Erythema; Female; Humans; Male; Middle Aged; Skin; Ultraviolet Rays; Young Adult
PubMed: 29098908
DOI: 10.1080/09546634.2017.1395797 -
The Journal of Dermatological Treatment May 2018Desoximetasone 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... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Administration, Topical; Adolescent; Adult; Aged; Desoximetasone; Drug Administration Schedule; Drug Compounding; Female; Gastrointestinal Diseases; Humans; Infections; Male; Middle Aged; Skin; Treatment Outcome; Ultraviolet Rays; Young Adult
PubMed: 29098900
DOI: 10.1080/09546634.2017.1395803 -
Dermatology Online Journal Aug 2019Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence.... (Review)
Review
BACKGROUND
Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence. Spray vehicles may offer, convenience, and strong efficacy.
METHODS
A literature review was conducted using keywords: clobetasol, desoximetasone, betamethasone, triamcinolone, corticosteroid, topical, spray, vehicles, treatment, and clinical trial.
RESULTS
For moderate-to-severe plaque psoriasis, 87% of subjects achieved an Overall Disease Severity (ODS) Score ≤2 at week two and 78% achieved an ODS ≤1 after four weeks with clobetasol propionate (CP) 0.05% spray compared to 17% and 3% in the control group, respectively (P<0.001). For desoximetasone 0.25% spray, 31%-53% with moderate-to-severe psoriasis achieve Physician's Global Assessment (PGA) score ≤1 at day 28 versus 5%-18% in the vehicle spray group (P<0.01). For betamethasone dipropionate 0.05% spray, 19% with mild-to-moderate plaque psoriasis achieved an Investigator's Global Assessment (IGA) score ≤1 or a 2-grade reduction in IGA versus 2.3% in vehicle group (P≤0.001). For mild-to-severe steroid responsive inflammatory dermatoses, 64% using triamcinolone acetonide 0.2% spray achieved clear or almost clear skin at day 14 (no P value reported). Adverse events including burning, irritation, and dryness were similar across all corticosteroids.
Topics: Administration, Cutaneous; Aerosols; Dermatitis; Glucocorticoids; Humans; Inflammation; Medication Adherence; Patient Preference; Psoriasis
PubMed: 31553858
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 -
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