Tazarotene Research Articles

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

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.

Binary Ethosomal Gel for Enhanced Transdermal Delivery of Tazarotene: Development, Refinement, in vitro Evaluation, and Skin Penetration Investigations

Background: Tazarotene (TZ) is a novel acetylenic class retinoid that selectively targets RARβ/γ. It is not particularly soluble or bioavailable, yet it is used to treat melanoma. Objective: To improve the tazarotene gel formula's transdermal distribution. Methods: TZ-incorporated binary ethosomes (TZ-BES) were developed for the current study. The cold technique and optimized Box-Behnken statistical design tools were used to synthesize the TZ-BES. The improved ethosome (TZ-BES13) was mixed with carbopol gel and tested for stability and ex vivo skin penetration, as well as viscosity, pH, spreadability, and drug content. Results: The optimal ethosomes (TZ-BES13) had a vesicle size of 168 nm, a PDI of 0.367, a zeta potential of -30 mV, and an entrapment effectiveness of 79.94%. TZ is enclosed in the ethosome matrix, as seen by the differential scanning calorimetry thermogram. FTIR shows that the TZ and additives are compatible. TZ-BES13-G2, the optimized TZ-BES13 gel, has a spreadability of 7.82 cm2, a pH of 6.52, a viscosity of 17235, and a drug content of 99.82±1.04%. Compared to the plan TZ-gel (43.54%), the TZ-BES13-G2 exhibits a much higher TZ release (89.22%). In 6 hours, rat abdomen skin permeability for TZ-BES13-G2 was 66.22±3.31%, much greater than that of plan TZ-gel (24.67%). The flow of TZ-BES13-G2 was 2.68 times greater than that of plan TZ-gel. The stability analysis showed that the formulation's properties had not changed significantly. Conclusion: Ethosomal gel offers an alternative mode of TZ administration when used topically.

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

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.

Tackling acne vulgaris by fabrication of tazarotene-loaded essential oil-based microemulsion: In vitro and in vivo evaluation

This study aimed to formulate and optimize an anti-acne drug namely tazarotene (TZR) in essential oil-based microemulsion (ME) using either Jasmine oil (Jas) or Jojoba oil (Joj). TZR-MEs were prepared using two experimental designs (Simplex Lattice Design®) and characterized for droplet size, polydispersity index, and viscosity. Further in vitro, ex vivo, and in vivo investigations were performed for the selected formulations. Results revealed that TZR-selected MEs exhibited suitable droplet size, homogenous dispersions, and acceptable viscosity, in addition to spherical-shaped particles in morphology. The ex vivo skin deposition study showed a significant TZR accumulation in all skin layers for the Jas-selected ME over the Joj one. Further, TZR didn't show any antimicrobial activity against P. acnes, however, it was boosted when it was incorporated into the selected MEs. The in vivo study results of the infected mice ears induced by P. acnes revealed that our selected MEs successfully reached a high level of ear thickness reduction of 67.1% and 47.4% for Jas and Joj selected MEs, respectively, versus only 4% for the market product. Finally, the findings confirmed the ability to use essential oil-based ME, particularly with Jas, as a promising carrier for topical TZR delivery in the treatment of acne vulgaris.

Novel Synergistic Approach: Tazarotene-Calcipotriol-Loaded-PVA/PVP-Nanofibers Incorporated in Hydrogel Film for Management and Treatment of Psoriasis.

Psoriasis is an autoimmune skin disease that generally affects 1%-3% of the total population globally. Effective treatment of psoriasis is limited because of numerous factors, such as ineffective drug delivery and efficacy following conventional pharmaceutical treatments. Nanofibers are widely being used as nanocarriers for effective treatment because of their multifunctional and distinctive properties, including a greater surface area, higher volume ratio, increased elasticity and improved stiffness and resistance to traction, favorable biodegradability, high permeability, and sufficient oxygen supply, which help maintain the moisture content of the skin and improve the bioavailability of the drugs. Similar to the extracellular matrix, nanofibers have a regeneration capacity, promoting cell growth, adhesion, and proliferation, and also have a more controlled release pattern compared with that of other conventional therapies at the psoriatic site. To ensure improved drug targeting and better antipsoriatic efficacy, this study formulated and evaluated a tazarotene (TZT)-calcipotriol (CPT)-loaded nanofiber and carbopol-based hydrogel film. The nanofiber was prepared using electrospinning with a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) K-90 polymeric blend that was later incorporated into a carbopol base to form hydrogel films. The prepared nanofibers were biochemically evaluated and in vitro and in vivo characterized. The mean diameters of the optimized formulation, i.e., TZT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-PVA/PVP-NF) and TZT-CPT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-CPT-PVA/PVP-NF) were 244.67 ± 58.11 and 252.31 ± 35.50 nm, respectively, as determined by scanning electron microscopy, and their tensile strength ranged from 14.02 ± 0.54 to 22.50 ± 0.03 MPa. X-ray diffraction revealed an increase in the amorphous nature of the nanofibers. The biodegradability studies of prepared nanofiber formulations, irrespective of their composition, showed that these completely biodegraded within 2 weeks of their application. The TZT-CPT-PVA/PVP-NF nanofibers exhibited 95.68% ± 0.03% drug release at the end of 72 h, indicating a controlled release pattern and following Higuchi release kinetics as a best-fit model. MTT assay, antioxidant and lipid profile tests, splenomegaly assessment, and weight fluctuation were all performed in the in vitro as well as in vivo studies. We found that the TZT-CPT-PVA/PVP-NF-based hydrogel film has high potential for antipsoriatic activity in imiquimod-induced Wistar rats in comparison with that of TT-PVA/PVP-NF nanofibers.

Microsponge based gel as a simple and valuable strategy for formulating and releasing Tazarotene in a controlled manner

This study aims to deliver Tazarotene (TZR) in a controlled manner to reduce adverse effects in the form of a microsponge-based gel. It adopts the methodology of a similar study by the undersigned authors with respect to the drug Clindamycin. Under both studies, the methodology used is emulsion solvent diffusion. Accordingly, we altered the concentrations of polymer and emulsifier to generate four formulations of TZR microsponges. Additionally, we used two types of emulsifiers and two types of solvents to develop two further microsponge formulations. We then studied the physical properties of each formulation, as well as drug-polymer interactions. Echoing findings from our prior study of Clindamycin, we found that microsponge formulations coded by T1 and T3 had superior production yield and entrapment efficiency, and their particle size was suitable for dermal application. As in the prior Clindamycin study, each of the T1 and T3 microsponge formulations were incorporated into a Carbopol gel and evaluated in vitro. The optimal formulation was found to be the microsponge formulation gel T8, which released 87.63% of TZR over 12 h. No significant interactions between the drug and excipients were found through Fourier transform infrared spectroscopy and differential scanning calorimetry.

Development and Evaluation of Topical Nanoemulgel Formulation of Tazarotene for Effective Treatment of Excision Wounds

Aim: The aim of the present investigation entails the development and evaluation of topical nanoemulgel formulation of tazarotene for effective treatment of excision wounds Background: Tazarotene (TZR) is a retinoid derivative marketed for the treatment of acne and psoriasis and the recent investigations indicate its excellent wound healing potential. Despite having magnificent wound healing potential, it suffers from pharmacokinetic limitations of low aqueous solubility and local bioavailability. Conventional marketed formulations of TZR have been reported to cause significant skin irritation and redness after its topical application. Keeping this in view, present investigation was designed to develop nanoemulsion based gel with intention to resolve the above mentioned pharmacokinetic and pharmacodynamic issues. Objective: The goal of the study was to develop a stable and effective tazarotene-loaded nanoemulgel for treating excision wounds which can also overcome the issues associated with the native drug. Methods: Various oils, surfactants and co-surfactants were selected on the basis of their solubilisation potential for tazarotene. Pseudoternary phase plots were constructed to obtain stable nanoemulsion region for various proportions of oil, surfactant: co-surfactant (Smix) and water and determine optimized concentration ranges for robust formulation of tazarotene. Various characterization parameters were studied to investigate the optimized formulation having desired attributes of nanoemulsion. Reducing power assay and phamacodymanic studies were conducted to determine the wound healing potential of developed nanoemulgel. Results: TZR loaded nanoemulsion was successfully developed with nano-sized globules using tea tree oil with Tween 20 as surfactant and PEG 400 as co-surfactant. Prepared nanoemulsions were thermodynamically stable and were further gellified using Carbopol 940 as biodegradable gelling polymer. Prepared gels showed good spreadability, drug permeation and stability. In vivo investigations demonstrated that optimized formulation successfully masked the irritant nature of tazarotene. Moreover, the pharmacodynamic evaluation of developed nanoemulsion gel revealed its significant analgesic, anti-inflammatory properties in addition to its markable wound contraction as compared to control. Conclusion: The results demonstrated potential of developed nanoemulgel over marketed formulation to overcome the drawbacks like redness and erythema. It also showed significant healing efficacy over other

Statistical Sequential Experimentation: Preliminary Mixed Factorial Design, I-Optimal Mixture Design Then Finally Novel Design Space Expansion for Optimization of Tazarotene Cubosomes.

ObjectiveThis study aims to illustrate the potential of sequential experimentation for statistically scientific based optimization of Tazarotene (TAZA) cubosomes.MethodsHot melt emulsification method was used for cubosomes preparation. A preliminary (3.2) mixed factorial design (MFD) was conducted to choose suitable types of stabilizer and surfactant that maximize entrapment efficiency (EE) and minimize particle size (PS). These chosen stabilizer and surfactant were to be used in the statistical design proposed for optimization of TAZA cubosomes (I-optimal mixture design) (IOMD). Glyceryl monooleate (GMO), stabilizer and surfactant amounts were the three mixture components (MixCs) studied in that design. Responses (EE, PS and drug percent released after 24 hours (Q24h)) were statistically analyzed. Numerical optimization using desirability function based on different responses’ importance was used to find an IOMD-optimized formulation (IOMD-OF) with the predetermined characters. Then, a novel statistical methodology of design space expansion was adopted to enhance Q24h. Suitable models to express EE, PS and Q24h were elucidated over the expanded mixture design (EMD) space. Validity of derived models was verified via prediction intervals and percent deviations of actual values from predicted ones for all the EMD design points. EMD was then navigated to find EMD-OF.ResultsAnalysis of MFD showed that Pluronic-F68 and polyvinyl alcohol were the best stabilizer and surfactant to be used. First stage optimization after IOMD analysis led to a formulation with unsatisfactory Q24h of 58.8%. After design space expansion adoption, re-analysis and re-optimization, a satisfactory EMD-OF having EE of 82.1%, PS of 273.0 nm and Q24h of 68.8% was found.ConclusionStatistical sequential experimentation with the novel design space expansion approach proved to be a successful paradigm for enhancing TAZA cubosomes optimization. Thus, this paradigm is expected to have promising future applications in various pharmaceutical formulations optimization.

Adjunctive Use of Halobetasol Propionate-Tazarotene in Biologic-Experienced Patients With Psoriasis.

Not all patients with psoriasis achieve a satisfactory response to their initial biologic monotherapy. Switching to a new biologic may be associated with new safety issues and additional costs. In this study, we assessed the effectiveness and safety of adjunctive halobetasol propionate (HP) 0.01%-tazarotene (TAZ) 0.045% lotion in adult patients with moderate to severe plaque psoriasis who had been receiving biologic monotherapy for 24 weeks or more but had inadequate responses. All participants received HP-TAZ lotion once daily for 8 weeks, then once every other day for 4 weeks, in addition to their ongoing biologics. This real-world study demonstrated that HP-TAZ lotion adjunctive to ongoing biologics is safe and effective and potentially a more economical alternative to switching biologics for patients with psoriasis with inadequate responses to biologic monotherapy.

DEVELOPMENT AND VALIDATION OF UV SPECTROSCOPIC METHOD FOR SIMULTANEOUS ESTIMATION OF TAZAROTENE AND HALOBETASOL PROPIONATE IN FIXED-DOSE COMBINATION

Simple, precise and accurate UV-Spectrophotometric simultaneous equation method for estimation of Halobetasol propionate (HALO) and Tazarotene (TAZA) were developed and validated as per ICH guidelines. This Method involves solving of simultaneous equations based on measurement of absorbance at two wavelengths 238 nm and 351 nm (λmax of HALO and TAZA) in methanol. HALO obey the Beer’s law in the concentration ranges 5-25μg/ml and TAZA (1- 5μg/ml). % Recovery for both the drugs were in the range of 98.46±0.854% to 99.21±0.688 for halo and 97.10±0.781 to 99.04±0.770 for TAZA respectively indicating excellent accuracy. The methods were precise, with a relative standard deviation of less than 2% for both drugs. The developed methods were validated according to ICH guidelines and values of accuracy, precision and other statistical analysis were found to be in good accordance with the prescribed values. Thus, method can be used for routine monitoring of drugs in industry for the assay of bulk drugs and commercial formulation.

Posttreatment maintenance of therapeutic effect with fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion for moderate-to-severe plaque psoriasis

Background The topical corticosteroid halobetasol propionate (HP) and retinoid tazarotene (TAZ) are effective in psoriasis treatment. Fixed-combination HP 0.01%/TAZ 0.045% lotion has demonstrated efficacy and safety in moderate-to-severe plaque psoriasis. Objective To investigate the maintenance of therapeutic effects after cessation of once-daily HP/TAZ treatment. Methods In two phase 3 studies (NCT02462070; NCT02462122), adults with moderate-to-severe psoriasis received HP/TAZ for 8 weeks. Data at week 12 were analyzed post hoc to evaluate posttreatment maintenance of treatment success (clear/almost clear skin), improvements in signs of psoriasis (erythema, plaque elevation, scaling), and reductions in affected body surface area (BSA). In a 52-week open-label study (NCT02462083), participants stopped HP/TAZ treatment after achievement of treatment success; data were analyzed post hoc to assess time to retreatment. Results Across all studies, most participants who achieved treatment success maintained this effect for at least one month posttreatment. Treatment effects were similarly maintained for improvements in signs of psoriasis and reductions in BSA. Some participants continued to improve after cessation of treatment. Maintenance of treatment success and time to retreatment were greater for participants who achieved clear skin. Conclusion HP/TAZ lotion provides therapeutic effects that persist after treatment cessation, supporting its use in long-term management of plaque psoriasis.

A Comparative Clinical Demonstration of the Spreadability of Tazarotene Lotion 0.045% versus Trifarotene Cream 0.005%

Abstract not available.

Novel Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Race

Abstract not available.

Efficacy and Safety of a Novel Tazarotene 0.045% Lotion in Females and Males With Moderate-to-Severe Acne

Abstract not available.

Fixed combination of tazarotene and betamethasone dipropionate for treatment of psoriasis vulgaris: The result of a phase 3, multicenter, randomized controlled trial.

Long-term use of corticosteroids or local use of tazarotene (TAZ) alone for the treatment of psoriasis cause safety issues and low compliance rates. Combining these two may optimize their efficacy and minimize safety concerns. This study aimed to evaluate the clinical efficacy and safety of a fixed combination of TAZ 0.05% and betamethasone dipropionate 0.05% (BM) for psoriasis vulgaris. A multicenter, randomized, single-blinded, controlled phase 3 clinical trial was conducted. A total of 600 Chinese subjects with psoriasis vulgaris were randomized (3:1:1) to TAZ/BM cream, TAZ gel or BM cream groups for 6weeks with an 8-week follow up. The primary efficacy assessment end-point was 75% improvement in Psoriasis Area and Severity Index (PASI-75) at 6weeks. Secondary outcome assessments included PASI-90, percentage of PASI decrease and so forth. Safety and treatment-related adverse events were monitored throughout the study. Our results demonstrated that the TAZ/BM group exhibited statistically significant superiority in PASI-75 over TAZ (6.74% vs 1.67%) within 2weeks. After 6weeks of treatment, PASI-75 was 44.94% in the TAZ/BM group while 19.17% and 35.00% in the TAZ and BM group, respectively. At the 8-week follow up, the relapse rate of the TAZ/BM group was significantly lower than the BM group (10.62% vs 29.63%, P=0.0269) though comparable with the TAZ group (10.00%). The most frequently reported treatment-related adverse event was mild to moderate level of skin irritation events. TAZ/BM combination has significant advantages over TAZ, including satisfying efficacy, rapid onset and reduced local stimulation. Meanwhile, compared with BM, it has the advantages of longer relief time and reduced clinical relapse rate. The TAZ/BM combination drug provides psoriatic patients an alternative drug with high efficacy and low relapse rate and safety concerns.

Halobetasol 0.01%/Tazarotene 0.045% Lotion for Moderate-to-Severe Psoriasis: Pooled Phase 3 Analysis of Males and Females

Halobetasol 0.01%/Tazarotene 0.045% Lotion for Moderate-to-Severe Psoriasis: Pooled Phase 3 Analysis of Males and Females

UV spectrophotometric method for simultaneous estimation of betamethasone valerate and tazarotene with absorption factor method: Application for in-vitro and ex-vivo characterization of lipidic nanocarriers for topical delivery.

The present study elucidates the development of an accurate, precise and simple simultaneous estimation method for the routine analysis of Betamethasone Valerate (BV) and Tazarotene (TZ). This combination is widely used in the treatment of psoriasis. No method has been reported so far for the simultaneous estimation of BV and TZ in topical dosage forms. The method proposed by this study for the quantification of BV and TZ is the Absorption factor method. The developed method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline. The validated method was found to be linear in a concentration range of 10-38μg/mL and 4-14μg/mL for BV and TZ respectively with a regression coefficient >0.990. The method was validated for accuracy and precision which revealed the recovery of >99.80% with RSD <2.0. The method was found to be precise with RSD <2% for inter and intraday. The developed method was employed for quantification of BV and TZ in lipid based nanocarriers formulation and their in-vitro drug release samples. Further, the developed method was successfully applied for the estimation of BV and TZ in the ex-vivo skin matrix. This showed that the method can sensitively determine the drugs in aqueous and biological samples.

Comparison of a Novel Tazarotene 0.045% Lotion to Tazarotene 0.1% Cream: Patient-Reported Outcomes from a Phase 2 Clinical Trial

Abstract not available.

Efficacy, Safety, and Tolerability of a Halobetasol 0.01%/Tazarotene 0.045% Fixed Combination in the Treatment of Moderate-to-Severe Plaque Psoriasis in a Hispanic Population: Post Hoc Analysis of Two Phase 3 Randomized Controlled Trials

Abstract not available.

Efficacy of Halobetasol 0.01%/Tazarotene 0.045% (HP/TAZ) Fixed Combination in the Treatment of Moderate Plaque Psoriasis: Indirect Comparison Between Pooled Phase 3 Trials of HP/TAZ and Oral Treatment (Apremilast)

Abstract not available.