A simple, rapid, cost-effective, and stability-indicating reverse phase high performance liquid chromatographic (RPHPLC) method was developed and validated for the simultaneous estimation of Tazarotene (TAZA) and Halobetasol propionate (HALO) in combined cream formulation. Chromatographic separation was achieved using a C18 column with an optimized mobile phase at a flow rate of 1.0 mL/min and detection at 254 nm. The method exhibited excellent linearity over the concentration range of 2–10 µg/mL for HALO and 1–5 µg/mL for TAZA, with correlation coefficients (r²) of 0.9994 and 0.999, respectively. The method was validated as per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines for parameters including linearity, accuracy, precision, robustness, specificity, limit of detection (LOD), and limit of quantitation (LOQ). Recovery studies showed results within 98–102%, and %RSD values for precision were less than 2%, indicating high reproducibility. Forced degradation studies under acidic, alkaline, oxidative, and thermal conditions demonstrated significant degradation without interference from degradation products, confirming the stability-indicating nature of the method. Assay results of marketed cream formulation were within acceptable limits. Hence, the developed RP-HPLC method is suitable for routine quality control and stability studies of combined TAZA and HALO pharmaceutical formulations.

ABSTRACT: Halobetasol propionate (HBT) is a topical corticosteroid used to manage Psoriasis. The current studies investigate microsponges-loaded gels of Halobetasol propionate. The HBT Microsponge was prepared by QESD method. Based on a preliminary trial, the polymer, surfactant and plasticizer were selected respectively as Eudragit RS-100, Poloxamer 407 and Propylene glycol. Microsponge was optimized by Box-Behnken design by selecting independent factors the drug-to-polymer ratio (A), the concentration of surfactant (B), the concentration of plasticizer (C), and the Stirring speed (D). These parameters were chosen to investigate their impact on dependent parameters, including the percentage of encapsulation efficiency (%EE, Y1), particle size (Y2), and percentage yield (Y3). Optimized microsponge containing HBT was converted into gel employing HPMC K100M as gelling agent to impart viscosity to the preparation and maintain the drug's activity by extending residence duration. Optimized HBT loaded microsponge-gel evaluated for Spreadability, viscosity, pH, In vitro diffusion study, Ex vivo permeation study and stability study. %EE, Pa. size and % yield of optimized microsponge was found to be 84.87±0.87%, 89.58±1.99 micron, 93.65±0.47% respectively.The porous nature of microsponge structure was confirmed by SEM analysis. The Spreadability and viscosity of optimized microsponge-based gel (MSPG-2) was found to be 4.1±0.07 g.cm/sec and 9748±14.12 cps. respectively. The pH was found to be favorable to skin condition would not produce any skin irritation. The drug content of optimized gel was found to be 98.8±0.57%. From the in-vitro and ex-vivo drug diffusion study shows that at the end of 12 hours Microsponge loaded gel diffuse more through the membrane as compared to marketed formulation. The product was stable up to 3 months which is confirmed by stability study.

Study on the absorption mechanism of glucocorticoids in the stratum corneum.

Hyperkeratotic plaque psoriasis represents a distinct morphological variant that is difficult to treat with topical therapies because thick lesions may impede the penetration of active ingredients. The immunoregulatory mechanisms of topical corticosteroids (TCSs) and tazarotene (TAZ) may contribute to combating hyperkeratosis and long-term remittance of psoriasis. A fixed-combination lotion containing the potent-to-superpotent TCS halobetasol propionate (HP, 0.01%) and TAZ (0.045%), indicated for the topical treatment of plaque psoriasis in adults, was developed to harness the therapeutic benefits of each active ingredient while minimizing their safety concerns. This review describes data supporting the efficacy of halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) and remittive effect after treatment cessation in patients with hyperkeratotic plaques. Pivotal trials demonstrate the superior efficacy and safety of HP/TAZ over each active ingredient alone. Furthermore, we summarize a recent clinical study, which showed that HP/TAZ reduces lesional levels of tumor necrosis factor alpha and interleukin 17A, critical proinflammatory cytokines involved in keratinocyte hyperproliferation and psoriasis pathogenesis. This review suggests that HP/TAZ is a valuable option for the topical treatment of severe hyperkeratotic plaques through its additive mechanisms targeting inflammation and keratinocyte regulation.

Scalp involvement in plaque psoriasis is accompanied by itching and scaling that reduce quality of life and exacerbate psoriatic-associated hair loss. Challenges for the topical treatment of scalp psoriasis include messy formulations that reduce patient adherence and dermal penetration in hair-bearing areas. This open-label study evaluated the efficacy of fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ, indicated for the topical treatment of plaque psoriasis in adults) in subjects with moderate-to-severe scalp psoriasis. Subjects applied HP/TAZ to the scalp once daily for 12 weeks and were evaluated at 4-week intervals. Endpoints included subject-reported scalp itch, investigator-reported psoriasis scalp severity index (PSSI), and investigator- and subject-reported hair and scalp assessments. From baseline, subjects experienced significant reductions in scalp itch and PSSI by week 12 (-49% and -93%, respectively; P≤0.001). Similarly, ratings for all investigator- and subject-assessed hair and scalp parameters were significantly improved from baseline at week 12 (P≤0.002 for all). No adverse events were reported. HP/TAZ is an efficacious treatment for scalp psoriasis, and reductions in psoriatic disease and itch may reduce scratching, leading to improvements in hair and scalp health.

A Canadian Real-World Study of Fixed-DOSE combination of Halobetasol Propionate 0.01%/Tazarotene 0.045% Lotion for the Treatment of Moderate-to-Severe Plaque Psoriasis.

ABSTRACT Utilizing chromatography with green chemistry principles helps minimize harm to people and the environment. Since its recent release, the new combination of tazarotene (TAZ) and halobetasol propionate has gained popularity. Crisaborole (CRB) has recently also shown potential for treating psoriasis and can be coformulated with drugs like TAZ and anthralin. Currently, no method has been reported for the simultaneous determination of these drugs. In addition, an environmentally friendly high‐performance liquid chromatography (HPLC) method for any of them has yet to be developed. The challenge arises mainly due to TAZ's strong retention on reversed phase (RP) columns, which prompts the use of high amounts of organic solvent. To develop a green isocratic HPLC‐photodiode array (PDA) method, the central composite and Box–Behnken quality‐by‐design approaches were employed to study the impact of various factors and their interactions on multiple responses. Since TAZ could not be eluted using micellar phases alone, ethanol was selected as an organic modifier due to its accessibility, environmental friendliness, and limited studies on its use in micellar HPLC. The separation was achieved using a mobile phase of 0.01 M Brij‐35, 0.143 M sodium dodecyl sulfate (SDS), and 0.015 M ammonium acetate (pH 4.95): ethanol (83:17, v/v) at a 1.5 mL/min flow rate. The method utilized the monolithic Chromolith performance RP‐C 18 column (100 mm × 4.6 mm × 5µm) at 40°C with a run time less than 10 min. The linear range established was (3.00–150.00 µg/mL) with limits of detection (0.59–0.78 µg/mL) and quantification (1.79–2.37 µg/mL). The proposed method was applied to different dosage forms (ointment, cream, lotion) after optimizing a microextraction procedure with recoveries > 98.5%. It scored 0.7 on analytical greenness (AGREE), 76 on modified Green Analytical Procedure Index (MoGAPI), and 82.5 on Blue Applicability Grade Index (BAGI). Comparing these scores with reported methods underlines the value of incorporating a scoring system into GAPI and evaluating methods from the blue and green perspectives.

Background: Psoriasis on hair-bearing body areas may be difficult to treat with topical therapy, as hair may reduce penetration of active ingredients.1 Patients may also experience disease rebound following cessation of corticosteroid therapy.2,3 An appropriate vehicle for hair-bearing areas may increase penetration, and a combination of corticosteroid and tazarotene may improve maintenance of treatment effect following cessation.4-6 Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) and HP 0.01% lotion are indicated for treatment of plaque psoriasis in adults7,8 and contain a vehicle optimized for penetration.6,9 Previously, a post hoc analysis demonstrated the efficacy and safety of HP/TAZ and HP in treating men with plaque psoriasis on the leg, a representative area with body hair.10 Here, we expand on the previous study by reporting maintenance of efficacy following treatment cessation in this population. Methods: In phase 3 trials, participants with moderate-to-severe plaque psoriasis were randomized to treatment or vehicle once daily for 8 weeks (HP/TAZ, n=276; vehicle, n=142; HP, n=285; vehicle, n=145). Participants were assessed at 2-week intervals and at 4 weeks after treatment cessation (week 12).11,12 In this post hoc analysis, treatment success (≥2-grade improvement in investigator’s global assessment score and score of clear or almost clear); erythema, plaque elevation, and scaling success (≥2-grade improvement for each); and safety were assessed in men with psoriasis on the leg treated with HP/TAZ (n=87) or HP (n=91). Maintenance of effect was defined as the proportion of participants who achieved treatment, erythema, plaque elevation, or scaling success at week 8 and maintained success at week 12. Men were assumed to have leg hair. Treatment comparisons were indirect. Results: Four weeks after treatment cessation, HP/TAZ–treated participants exhibited increased rates of treatment success (week 8, 35.3%; week 12, 37.2%) and erythema success (week 8, 37.4%; week 12, 48.4%), whereas HP-treated participants exhibited decreased rates (treatment success: week 8, 35.5%; week 12, 23.1%; erythema success: week 8, 50.6%; week 12, 36.5%). HP/TAZ–treated participants exhibited less attrition in plaque elevation and scaling success after treatment cessation (week 8, 57.4% and 56.3%; week 12, 55.1% and 55.8%, respectively) versus HP-treated participants (week 8, 53.1% and 61.7%; week 12, 39.8% and 41.6%, respectively). For all outcomes, a greater proportion of participants receiving HP/TAZ achieved maintenance of effect from weeks 8 to 12 compared with participants receiving HP (range: HP/TAZ, 74%-85%; HP, 56%-62%). No new safety signals were identified. Conclusions: Following treatment cessation of HP/TAZ, men with plaque psoriasis on the leg experienced further disease improvement and maintained treatment effects at greater rates than those treated with HP, suggesting that tazarotene combined with HP provides prolonged efficacy in hair-bearing areas.

甾体激素类的污染及危害问题不容忽视,为了实现更加全面、准确的高通量分析,研究建立了固相萃取-超高效液相色谱-串联质谱同时测定水中糖皮质激素类(48种)、盐皮质激素类(1种)、雄激素类(4种)及孕激素类(8种)等共61种激素成分的多残留分析方法。采用HC-C18固相萃取柱对大体积(1 L)水样中的目标化合物进行富集净化,乙腈洗脱,以BEH C18色谱柱分离,以0.1%甲酸水溶液和乙腈为流动相梯度洗脱,用超高效液相色谱-串联质谱仪分离和检测。质谱采用电喷雾正离子电离、多反应监测模式,外标法定量。61种激素在相应的范围内,线性关系良好,相关系数均大于0.99,方法检出限为0.05~1.50 ng/L,在低、中、高3个加标水平下的回收率为62.3%~125.2%,相对标准偏差为1.1%~10.5%。将建立的方法应用于太湖流域的地表水、相关区域的地下水以及末梢水的分析,部分地表水和地下水中检出了可的松、丙酸氟替卡松、环索奈德、倍他米松双丙酸酯、氯倍他松丁酸酯、戊酸双氟可龙、卤倍他索丙酸酯、异氟泼尼龙、二氟孕甾丁酯和己酸羟孕酮等10种成分,其余51种成分未检出。该方法操作简单,灵敏度高,准确度好,对后续水安全的监测以及溯源调查有重要意义。对水中激素水平进行了地区分析,提出了未来污水处理工艺应将激素残留作为目标物进行针对性处理的建议。

53779 Fixed-Combination Halobetasol Propionate 0.01%/Tazarotene 0.045% and Halobetasol Propionate 0.01% Lotions for Plaque Psoriasis on Lower Extremities With Body Hair

53803 Early and Sustained Efficacy of Fixed-Combination Halobetasol Propionate and Tazarotene Lotion in Participants with Moderate-to-Severe Scaling or Plaque Elevation

An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. The expert panel reached consensus on 20 statements. Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence.

Background: Psoriasis is a chronic, genetically determined inflammatory skin condition characterized by erythematous plaques with silvery scales, affecting about 2% of the global population. It significantly impacts patients' quality of life, encompassing physical, emotional, and psychosocial dimensions. While the use of topical corticosteroids (TCS) with tazarotene has shown benefits in plaque psoriasis treatment, limited data are available on the efficacy of combining halobetasol and tazarotene. Objective: This study aimed to compare the efficacy of Tazarotene 0.045% cream (TAZ) versus Halobetasol Propionate 0.01% lotion (HP) for the treatment of scalp psoriasis at a tertiary care hospital in Karachi, providing insight into their comparative effectiveness and informing clinical decision-making. Methods: A randomized control trial was conducted at the Dermatology Department of Jinnah Postgraduate Medical Centre, Karachi, from August 2022 to February 2023. Ninety participants with scalp psoriasis were recruited and randomly assigned to two groups: Group A (n=45) received Tazarotene 0.045% cream, and Group B (n=45) received Halobetasol Propionate 0.01% lotion, both applied once daily for 6 weeks. The primary outcome was the change in Investigator's Global Assessment (IGA) score from baseline to week 6. Data analysis was performed using SPSS version 25, focusing on descriptive statistics and inferential analyses to evaluate treatment efficacy. Results: The study observed a significant reduction in IGA scores from baseline in both groups, with Group A (TAZ) showing a decrease from 3.89 ± 0.68 to 1.29 ± 0.62 and Group B (HP) from 3.87 ± 0.66 to 2.49 ± 0.62. The paired difference in IGA scores indicated a more pronounced improvement in the TAZ group (2.60 ± 0.75) compared to the HP group (1.37 ± 0.57), with significant differences between the groups (p<0.0001). Treatment success was observed in 82.2% of participants in the TAZ group compared to 51.1% in the HP group, with an odds ratio of 4.424 (95% CI: 1.690—11.578; p=0.002). Conclusion: Tazarotene 0.045% cream demonstrates significantly greater efficacy in treating scalp psoriasis compared to Halobetasol Propionate 0.01% lotion. The findings suggest Tazarotene as a preferable treatment option for scalp psoriasis, offering a better therapeutic outcome.

ObjectiveFixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved for the treatment of plaque psoriasis in adults, with a demonstrated efficacy and safety profile in phase 3 trials. This study examined the effect of HP/TAZ on the reduction of tumor necrosis factor alpha (TNF-α) and interleukin 17 A (IL-17A) and its correlation to psoriasis improvement.Materials and methodsTen adults with mild-to-moderate plaque psoriasis and 2 symmetrical plaques self-applied HP/TAZ (treated plaque) or vehicle lotion (untreated plaque) for 12 weeks. At baseline and each study visit (weeks 2, 4, 8, and 12), Investigator’s Global Assessment (IGA) score and erythema, scaling, and induration were assessed. Additionally, D-squame tape strips were utilized to quantify TNF-α and IL-17A in target lesions by enzyme-linked immunosorbent assay.ResultsSignificant improvements in mean IGA score in HP/TAZ–treated compared with untreated plaques were evident at week 2 and maintained through week 12 (p < 0.003). HP/TAZ significantly reduced TNF-α levels at weeks 4 through 12 (p < 0.03) and IL-17A levels at weeks 2 through 8 (p < 0.05) in treated compared with untreated plaques.ConclusionsHP/TAZ was highly effective in treating psoriasis plaques and, although HP/TAZ is not a biologic, effectively reduced cytokine-associated inflammatory markers that drive psoriatic disease.

SA56 Canadian Expert Consensus on Use of Halobetasol Propionate/Tazarotene Lotion for Plaque Psoriasis

Figure 3. Affected BSA reduction (A) and treatment success (B) at week 8. ***P<0.001 vs vehicle. BSA, body surface area; HP, halobetasol propionate; IGA, Investigator's Global Assessment. a No imputation of missing data. b Defined as ≥2-grade reduction from baseline in IGA score and a score of "clear" or "almost clear." Values have been adjusted for multiple imputation.

Topical therapies are commonly used to treat psoriasis, either as monotherapy for milder disease or as adjuncts to systemic and biologic drugs. Topical steroids and tazarotene are both options for topical psoriasis treatment, but as monotherapies, they are associated with adverse events (AEs) that make adherence to prescribed treatment challenging. In addition, the topical vehicles may have an unappealing appearance or texture that proves impractical for patients. Consequently, patients may not use treatments as prescribed. This noncompliance can lead to a frustrating cycle of treatment, discontinuation, and retreatment without achieving treatment goals. Psoriasis is a chronic disease; thus, topical treatment options are needed that address these barriers to use and promote long-term adherence, making satisfactory improvement of psoriasis more attainable. In this review, we discuss patient preferences for topical therapies with vehicles that are moisturizing, nongreasy, and quickly absorbed. We then introduce the vehicle formulation of fixed-dose combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion, which has a unique matrix mesh formulation that enhances uniform absorption, allows for efficient drug delivery, and aligns with patient preferences. In addition to vehicle benefits, the combination of HP and TAZ has been shown to minimize AEs seen with either monotherapy. In clinical trials, HP/TAZ was efficacious and associated with a low rate of AEs with long-term use. This evidence supports the use of HP/TAZ as a topical treatment for patients with psoriasis facing challenges adhering to prescribed treatments and looking to break the cycle of unsatisfactory treatment outcomes. J Drugs Dermatol. 2023;22(3):247-251. doi:10.36849/JDD.7399.

IntroductionTo date, there have been no head-to-head clinical studies comparing calcipotriol 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) aerosol foam and halobetasol propionate 0.01% plus tazarotene 0.045% (HP/Taz) lotion for the treatment of plaque psoriasis. However, the efficacy of 4 weeks of Cal/BD foam and 8 weeks of HP/Taz lotion has been compared using a matching-adjusted indirect comparison (MAIC) approach. Here, we compare the efficacy and safety of Cal/BD foam and HP/Taz lotion for up to 52 weeks.MethodsAn unanchored MAIC was conducted using individual patient data from the PSO-LONG Cal/BD foam trial and a 52-week, open-label phase 3 study of HP/Taz lotion (NCT02462083). Key outcomes of interest were Physician’s Global Assessment (PGA) success (PGA 0/1 with ≥ 2-point improvement) after 4 or 8 weeks of open-label therapy; the proportion of patients who had body surface area affected (BSA) ≤ 3 after open-label therapy who maintained BSA ≤ 3 to week 52; and adverse events (AEs).ResultsAfter matching, patients were statistically significantly more likely to have PGA success after 4 weeks of Cal/BD foam than after 8 weeks of HP/Taz lotion (84.5% versus 54.4%; p < 0.01). At week 52, 92.5% and 92.4% of patients receiving proactive and reactive Cal/BD foam, respectively, maintained BSA ≤ 3, compared with 49.3% of those treated with HP/Taz lotion (both p < 0.01). Treatment-related AEs, AEs leading to withdrawal, and AEs associated with drug application (dermatitis, application site pain, and pruritus) were significantly rarer with Cal/BD foam than with HP/Taz lotion (all p < 0.01).ConclusionsCal/BD aerosol foam demonstrated significantly greater efficacy than HP/Taz lotion, and had a more favorable safety profile, compared with HP/Taz lotion, for up to 52 weeks. Proactive Cal/BD foam maintenance therapy and reactive use of Cal/BD foam following relapse both had significant advantages over HP/Taz lotion.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00824-9.

ABSTRACT Introduction Halobetasol propionate foam has been established as an efficacious and easy-to-use topical treatment for adults with plaque psoriasis. Its recent approval in the United States expanded its use for adolescents from ages 12 to 17 years old. Areas covered We briefly summarize the chemistry of halobetasol and review clinical trials involving halobetasol propionate 0.05% foam to evaluate its efficacy and safety profile with a specific focus on adolescents with plaque psoriasis. Expert opinion Halobetasol propionate 0.05% foam is an effective and cosmetically elegant superpotent topical corticosteroid, with a tolerable safety profile in adolescents. The use of this foam offers another option to address patient-specific needs and preferences, adding to the toolbox of currently available treatments for adolescent psoriasis.

33385 A polymeric emulsion of halobetasol propionate and tazarotene in the treatment of palmoplantar psoriasis