Betamethasone Valerate Research Articles

Reformulations of well-known active ingredients in the topical treatment of psoriasis vulgaris can improve clinical outcomes for patients.

Although the majority of patients with psoriasis vulgaris are treated exclusively with topical therapies, research to develop more effective topical therapies that are associated with higher patient satisfaction has lagged behind the development of systemic agents. The aim of this literature review was to determine whether there is documented evidence that applying an innovative approach to improving the formulation of active ingredients commonly used in the topical treatment of psoriasis can have a positive effect on clinical outcomes and patient-reported outcomes (PROs). The Embase and PubMed databases were searched for articles published between 2001 and 2016 that made direct head-to-head comparisons of different formulations of an active pharmaceutical ingredient (API), focusing on clinical outcomes and PROs. In total, 22 publications on APIs or API combinations met the eligibility criteria (19 head-to-head clinical trials, one pooled analysis, one health-economic modelling study and one systematic review). Significant clinical benefit associated with the use of a reformulated API over an older formulation was reported in three trials of clobetasol propionate, one trial of calcipotriol, three trials of betamethasone and five trials/pooled analyses of calcipotriol/calcipotriene + betamethasone dipropionate (Cal/BD) formulations. Significantly improved PROs associated with the use of a reformulated API over an older formulation were reported in three trials of clobetasol propionate, one trial of betamethasone valerate and two trials of Cal/BD formulations. These results demonstrate that the innovative reformulation of APIs used in the treatment of psoriasis can produce therapies that attain significantly improved clinical outcomes and PROs. This suggests that improvement in topical therapy for psoriasis need not only to be achieved by the identification of new targets and the development of new APIs, but that improvement in the vehicle used to deliver existing APIs has the potential to result in significant clinical and patient benefits.

Assessing the effectiveness of topical betamethasone to treat chronic chilblains: a randomised clinical trial in primary care.

GPs prescribe topical corticosteroids to patients with chronic chilblains despite poor evidence for their effectiveness. The authors of the current study therefore decided to assess the effectiveness of topical steroids in a primary care setting. To assess the effectiveness of topical application of betamethasone valerate 0.1% cream in patients with chronic chilblains. A placebo-controlled, double-blind, crossover, randomised clinical trial in a Dutch primary care setting. The study population consisted of 34 participants suffering from chronic chilblains. Intervention was topical application of betamethasone valerate 0.1% cream twice a day for 6 weeks compared with placebo. Primary outcome was the visual analogue scale on complaints (VOC). Secondary outcome was the visual analogue scale on disability (VOD). Both were assessed with a diary of daily scores on a 100 mm visual analogue scale. The authors took ambient temperatures into account, checked for a carry-over effect, performed additional analysis, and monitored adverse effects. On the primary outcome mean VOC, there was a difference of 0.56 mm (95% confidence interval [CI] = -2.88 to 3.99 mm) in favour of placebo (P = 0.744). On the secondary outcome mean VOD, there was a difference of 0.88 mm (95% CI = -2.22 to 3.98 mm) in favour of placebo (P = 0.567). This study found no carry-over effect and no adverse effects. In this study, topical betamethasone was not superior to placebo in the treatment of chronic chilblains. Topical betamethasone should not be used for chronic chilblains without new evidence.

Simultaneous Determination of Cinchocaine Hydrochloride and Betamethasone Valerate in Presence of Their Degradation Products.

Cinchocaine hydrochloride (CIN) and betamethasone valerate (BMV) are co-formulated in pharmaceutical formulations that could be used for local treatment of hemorrhoids. Both drugs are susceptible to hydrolytic degradation. Two sensitive and precise stability-indicating chromatographic methods were developed for the simultaneous determination of both active pharmaceutical ingredients. The developed methods were applied for quantitation of CIN and BMV in their pure forms, in presence of their corresponding degradation products and in their pharmaceutical formulation. The first method was a high performance liquid chromatographic (HPLC) one, separation and quantitation was achieved using a Waters Spheriosorb® 5 μm ODS2 C18 analytical column and an isocratic mobile phase formed of acetonitrile-acetate buffer (pH 6.5 ± 0.1) in a ratio of (55:45, v/v). The mobile phase was pumped at a flow rate of 1.2 mL/min. UV-detection was done at 240 nm using photodiode array detector. The second method was based on thin layer chromatography (TLC) fractionation coupled with densitometric determination. Separation was done on high performance thin layer chromatography (HPTLC) silica gel 60F254 plates using a developing system formed of chloroform-toluene-ethanol-acetic acid in a ratio of (4.5:4.5:1:1, by volume). The separated bands were scanned densitometrically at 240 nm. For the HPLC method, linearity was confirmed over concentration ranges of 4-300 and 4-350 μg/mL for CIN and BMV, respectively. For the HPTLC-densitometric method, the obtained ranges were 0.5-12 and 0.5-10 μg/band for CIN and BMV, respectively. The developed methods were optimized and validated according to the ICH guidelines. CIN acid degradation products were separated and identified by mass spectroscopy. The developed HPLC method was used to study the kinetics of acid and alkali degradation of the both drugs. The results obtained were statistically analyzed and compared with those obtained by applying the official methods for both drugs.

Bioequivalence Methodologies for Topical Drug Products: In Vitro and Ex Vivo Studies with a Corticosteroid and an Anti-Fungal Drug

ABSTRACTObjectiveTo examine whether in vitro and ex vivo measurements of topical drug product performance correlate with in vivo outcomes, such that more efficient experimental approaches can be reliably and reproducibly used to establish (in)equivalence between formulations for skin application.Materials and MethodsIn vitro drug release through artificial membranes, and drug penetration into porcine skin ex vivo, were compared with published human in vivo studies. Two betamethasone valerate (BMV) formulations, and three marketed econazole nitrate (EN) creams were assessed.ResultsFor BMV, the stratum corneum (SC) uptake of drug in 6 h closely matched data observed in vivo in humans, and distinguished between inequivalent formulations. SC uptake of EN from the 3 creams mirrored the in vivo equivalence in man (both clinically and via similar tape-stripping experiments). However, EN clearance from SC ex vivo did not parallel that in vivo, presumably due to the absence of a functioning microcirculation. In vitro release of BMV from the different formulations did not overlap with either ex vivo or in vivo tape-stripping data whereas, for EN, a good correlation was observed. No measurable permeation of either BMV or EN was detected in a 6-h in vitro skin penetration experiment.ConclusionsIn vitro and ex vivo methods for topical bioequivalence determination can show correlation with in vivo outcomes. However, these surrogates have understandable limitations. A “one-size-fits-all” approach for topical bioequivalence evaluation may not always be successful, therefore, and the judicious use of complementary methods may prove a more effective and reliable strategy.

Stability of a novel corticosteroid nasal irrigation solution: betamethasone 17-valerate added to extemporaneously prepared nasal irrigation solutions.

There are no commercially available nasal irrigation solutions containing corticosteroids. Instead, such preparations are extemporaneously prepared by adding existing corticosteroid formulations to nasal irrigation solutions. The stability of the corticosteroid betamethasone 17-valerate (B17V), in nasal irrigation solutions of different compositions and pH and stored under different temperatures, was studied to determine the optimal choice of solution and storage conditions. Triplicate extemporaneous preparations made with B17V were prepared by adding a predetermined volume of B17V lotion to each nasal irrigation solution: normal saline (NS), sodium bicarbonate (NaHCO3 ) powder dissolved in tap water, and a commercially available powder mixture (FLO Sinus Care Powder), dissolved in tap water or pre-boiled tap water. Preparations were stored at 30°C and 4°C. Sampling was carried out at 0, 1, 2, 6, and 24 hours. The concentrations of B17V and its degradation compound, betamethasone 21-valerate (B21V), were determined by high-performance liquid chromatography. Preparations stored at 30°C contained a lower amount of B17V and higher amount of B21V than those stored at 4°C. B17V stability in nasal irrigation solutions decreased in the following order: NS, FLO in fresh tap water, FLO in pre-boiled tap water, and NaHCO3 . The degradation rate of B17V increased with higher storage temperature and higher pH. B17V is most stable when added to NS and least stable in NaHCO3 solution. FLO solution prepared with either cooled boiled water or tap water is an alternative if administered immediately. Storage at 4°C can better preserve stability of B17V, over a period of 24 hours.

A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of Vitiligo Patients.

Background:Vitiligo, a common disorder of depigmentation, is often difficult to treat. Corticosteroids are known to be effective, but with modest results. Although simvastatin has been reported to be effective for immunorelated dermatologic disorders including vitiligo, controlled trials are lacking. This study was conducted to compare the efficacy of topical betamethasone valerate 0.1% cream (as a standard method of treatment for vitiligo) versus a combination of betamethasone valerate plus oral simvastatin in the treatment of vitiligo.Materials and Methods:Eighty-eight subjects with symmetric vitiligo who had body surface involvement up to 20% were divided randomly into two groups. Group A were treated with betamethasone valerate 01% cream twice daily and Group B with betamethasone valerate 01% cream twice daily and oral simvastatin 80 mg daily for 12 weeks. Finally, 46 patients completed treatment after 12 weeks in both groups. The results were evaluated by a blind dermatologist using Vitiligo Area Scoring Index (VASI) score at baseline, 4th, 8th, and 12th week of treatment. In a similar way, subjective assessment performed by patients based on photo evaluation at the end of the study.Results:Despite a continuous reduction in VASI score in both groups, according to both physician (P = 0.13) and patient (P = 0.374) assessment oral simvastatin was not statistically more effective than conventional treatment of vitiligo.Conclusion:This study indicates that oral simvastatin is not associated with significant impacts in the treatment of vitiligo as compared to other inflammatory dermatologic conditions such as psoriasis. Indeed, other studies should be initiated regarding exact molecular and cellular effects of statins in the treatment of vitiligo.

Atorvastatin as an adjuvant with betamethasone valerate reduces disease severity and cardiovascular risks in Psoriasis.

Objectives:To evaluate the effect of Atorvastatin as an adjuvant with betamethasone valerate on disease severity and cardiovascular risks in chronic plaque type psoriatic patients.Methods:It is an interventional study conducted in Pharmacology Department of BMSI, JPMC with the collaboration of Dermatology Department of JPMC, Karachi. The duration of study was from June 2013 to June 2016. Seventy five psoriatic patients were prescribed Tablet Atorvastatin 40-20 mg/day (40mg for first three months twice daily followed by 20mg once daily for the next three month) plus topical Betamethasone Valerate 0.1% once daily for 6 months (three week apply than one week interval). The efficacy and safety profile of drugs was measured by PASI, DLQI, hsCRP, LFTS and Lipid profile.Results:The percentage change of PASI is 86.749±0.547, DLQI is 82.697±.2.61 and hsCRP is 40.371±8.505, which showed highly significant improvement in patient at the end of last follow up. LFTs and CPK for safety profile of therapy showed non-significant results.Conclusion:Atorvastatin used as an adjuvant therapy with currently existing standard therapy (topical betamethasone) in patients having mild to moderate plaque type psoriasis reduces disease severity and cardiovascular risks.

Green Ion Selective Electrode Potentiometric Application for the Determination of Cinchocaine Hydrochloride in Presence of Its Degradation Products and Betamethasone Valerate: A Comparative Study of Liquid and Solid Inner Contact Ion-Selective Electrode Membranes

The sustainable and green chemistry principles enable scientists to protect and benefit the economy, people and the planet by finding creative and innovative ways to reduce waste, conserve energy, and discover replacements for hazardous substances. In this work, an environmentally friendly ion selective electrode (ISE) potentiometric method was developed for the determination of cinchocaine hydrochloride (CIN) in presence of its degradation products either in bulk powder or in its combined pharmaceutical formulation with betametahsone valerate. Two novel CIN-selective electrodes were fabricated and evaluated. The fabrication of electrodes was based on sodium tetrakis [3,5-bis (trifluoromethyl)phenyl]borate as a cationic exchanger in a PVC matrix with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer and using 2-hydroxy propyl-β-cyclodextrin (2-HP β-CD) as an ionophore. A comparative study was conducted using two designed CIN-selective electrodes; a conventional liquid inner contact, sensor 1, and a glassy carbon solid contact electrode, sensor 2. Sensor 1 has a linear dynamic range of 3.0 × 10−5 mol L−1 to 1.0 × 10−2 mol L−1, with a Nernstian slope of 54.89 mV/decade and a detection limit of 5.01 × 10−6 mol/L. Sensor 2 shows linearity over the concentration range of 1.0 × 10−5 mol L−1 to 1.0 × 10−2 mol L−1, with a Nernstian slope of 57.01 mV/decade and a limit of detection of 2.51 × 10−6 mol L−1 which is much improved as a result of diminishing ion fluxes in this solid contact ion-selective electrode. The present electrodes show clear selectivity for CIN from several inorganic, structurally related organic molecules, sugars, co-formulated drug, some common drug excipients and its degradation products. The results obtained by the proposed sensors were statistically analyzed and compared with those obtained by official method. No significant difference for either accuracy or precision was observed.

Contact allergy in the population of patients with chronic inflammatory dermatoses and contact hypersensitivity to corticosteroids.

IntroductionClinical studies indicate that contact allergy to glucocorticosteroids (GCS) is not rare and has been increasingly reported over the past decade. Among the risk factors for developing contact hypersensitivity to topical corticosteroids, chronic inflammatory skin diseases and polyvalent contact allergy seem to be most important.AimTo present the structure of contact allergy in the population of patients with chronic inflammatory dermatoses (CID) and contact hypersensitivity to corticosteroids.Material and methodsTwenty-seven patients with contact allergy to GCS and chronic inflammatory dermatoses were patch tested with 28 European Baseline Series allergens and 8 corticosteroid allergens. This study group consisted of 5 patients with atopic dermatitis (AD), 15 patients with contact eczema (CE) and 7 with chronic leg eczema (CLE). Nineteen (70.4%) patients were females and 8 (29.6%) were males.ResultsIn the study group, the most sensitizing non-steroidal allergens were nickel sulfate (51.8%), cobalt chloride (33.3%) and balsam of Peru (29.6%). The most sensitizing corticosteroid allergens were budesonide (77.8%), betamethasone valerate and clobetasol propionate (55.5% each). A total of 77.8% of patients allergic to GCS also showed sensitivity to at least one non-steroidal allergen from the European Baseline Series.ConclusionsThe most important risk factors for developing contact allergy to corticosteroids appear to be chronic inflammatory dermatoses, long disease duration, extended on-and-off topical corticosteroid use, patients presenting two or more positive patch test results and polyvalent contact allergy to metal salts and to other non-steroidal haptens.

Differences in therapeutic effects of topically applied corticosteroid and tacrolimus on atopic dermatitis-like symptoms in NC/Nga mice

BackgroundTopical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood. ObjectiveThis study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms. MethodsAD-like dermatitis was induced in the dorsal skin of NC/Nga mice by repeated topical application of Dermatophagoides farinae body (Dfb) ointment twice weekly for three weeks. Mice with dermatitis scores over 5 were divided into five groups with equal dermatitis scores and treated with BMV, CBP, TAC, or Vaseline (Vas) once daily for two consecutive days, or were not treated (NT). Scratching behavior was analyzed using a SCLABA®-Real system. Transepidermal water loss (TEWL) before and after treatment was measured using a Tewameter® TM210. Skin collected from each group was analyzed histologically. ResultsAfter the second treatment, dermatitis showed significantly greater improvement in the CBP and TAC-treated groups than in the Vas-treated and NT groups. The numbers of scratching bouts were significantly lower in CBP and TAC-treated mice than in Vas-treated mice. TEWL was significantly lower in TAC-, but not in CBP-, treated mice than in Vas-treated mice. Immunohistochemical examination showed that BMV, CBP and TAC did not reduce the increased densities of epidermal protein gene product 9.5- and substance P-immunoreactive fibers. The numbers of dermal CD4-immunoreactive T cells were significantly lower in BMV and CBP-treated mice than in Vas-treated and NT mice. The numbers of dermal eosinophils were significantly lower in BMV, CBP and TAC-treated mice than in Vas-treated and NT mice, with CBP showing the strongest effect. CBP significantly reduced epidermal thickness compared with Vas and NT. There were no significant differences in the numbers of interleukin-31-immunoreactive cells and mast cells, or in expression of epidermal thymic stromal lymphopoietin among all five groups. ConclusionThe therapeutic potency of TAC against AD-like symptoms, including pruritus, is equal to that of the corticosteroid CBP. Epidermal innervation of sensory nerves itself might not be related to the therapeutic effects of topical tacrolimus and corticosteroids in its early phase.

Palmarplantar erythrodysesthesia in the patients with oncological pathology treated with multikinase inhibitors and the method for its correction

Introduction. The modern anti-tumour preparations from the group of multikinase inhibitors exhibit the high clinical effectiveness. Courses of therapy with such medications are indispensable and vitally important for the treatment of the patients presenting with oncological pathology but, unfortunately, happen to give rise to the development of a toxic reaction in the form of рalmar-plantar erythrodysesthesia which not infrequently prevents the completion of the full-scale treatment. The determination of the adequate skin condition is an indispensable component of the combined treatment of the oncological patients. Materials and methods. The present study included 9 patients treated with various preparations from the group of multikinase inhibitors. All of them developed toxic cutaneous reactions in the form of grade II-III palmar-plantar erythrodysesthesia which was corrected with the use of thioctic acid-based preparation at a daily dose of 600 mg given during 14 days in the combination with pharmaphoresis of the cream containing 0.1% of betamethasone valerate. Results. The use of the proposed therapeutic modality resulted in the reduction of the severity of the clinical manifestations of palmar-plantar erythrodysesthesia, such as erythema, infiltration, desquamation, fissures, etc. Simultaneously, the treatment eliminated certain subjective symptoms including pruritus, pain, and paresthesia. Taken together, these effects significantly improved the patients’ condition and allowed the course of antitumour therapy to be totally completed. Conclusion. The patients presenting with palmar-plantar erythrodysesthesia should be managed with the use of multikinase inhibitors in the combination with the oral administration of a thioctic acid-based preparation and local pharmaphoresis of the cream containing 0.1% of betamethasone valerate.

Topical corticosteroid abuse on face: a clinical study of 100 patients

<p class="abstract"><strong>Background:</strong> Prolonged and uninterrupted use of topical corticosteroids on face is globally prevalant and this misuse has reached monstrous proportion in India. The topical corticosteroid abuse leads to various local adverse effects on face which are difficult to treat. The aim of this study was to ascertain the magnitude, demographics, cause and adverse effects of TC abuse on the face in the dermatology out-patient department.</p><p class="abstract"><strong>Methods:</strong> A total of 100 patients with history of topical corticosteroid abuse on face for a minimum period of one month were enrolled in this study.<strong></strong></p><p class="abstract"><strong>Results:</strong> In our study, majority of the patients were females (76%) and the most common age group was 21-30 years with 49% patients. The duration of application was <6 months (45%) in majority of patients. Most common topical corticosteroids abused were betamethasone valerate in 49% and clobetasol propionate in 40% cases.</p><strong>Conclusions:</strong> Topical corticosteroid abuse on face is quite common with varied presentation. There is need to take urgent remedial steps and increase awareness about this problem in general population.

Analysis of salicylic acid, arbutin and corticosteroids in skin whitening creams available in Pakistan using chromatographic techniques.

A simple, new and efficient reversed-phase high-performance liquid chromatography method was developed and validated for the separation of most popular ingredients in skin whitening creams. For RP-HPLC analysis, a Hibar(®) C18 250 mm × 4.6 mm, 5 μm column (Merck Millipore, Carolina, USA) as stationary phase with a mobile phase consisting a mixture of acetonitrile, methanol and water 40 : 40 : 20 (pH 7.0), respectively, at flow rate of 0.8 mL min(-1) (total run time 10 min) at room temperature was used. Detection was performed at 254 and 280 nm using photodiode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification. The method results in excellent separation of skin whitening agents in cosmetic creams. The method is specific for salicylic acid, arbutin, cortisone, hydrocortisone, betamethasone valerate and betamethasone dipropionate. The calibration curve of skin whitening agents was linear with the regression analysis showed r(2) ≥ 0.999. %RSD for inter- and intraday precision were determined as 0.461 and 0.329 for salicylic acid, 0.427 and 0.317 for arbutin, 0.360 and 0.346 for cortisone, 0.336 and 0.350 for hydrocortisone, 0.463 and 0.339 for betamethasone valerate and 0.385 and 0.372 for betamethasone dipropionate, respectively. LOD and LOQ were calculated as 0.48 and 1.20 μg mL(-1) for salicylic acid, 0.09 and 0.22 μg mL(-1) for arbutin, 0.07 and 0.18 μg mL(-1) for cortisone, 0.06 and 0.24 μg mL(-1) for hydrocortisone, 0.07 and 0.20 μg mL(-1) for betamethasone valerate and 0.02 and 0.06 μg mL(-1) for betamethasone dipropionate. The recovery of skin whitening agents were 97.18% for salicylic acid, 97.99% for arbutin, 98.30% cortisone, 97.63% for hydrocortisone, 98.65% for betamethasone valerate and 98.18% for betamethasone dipropionate, respectively. According to this study, salicylic acid is present in 87.88% skin whitening creams, arbutin in 96.97%, cortisone in 60.60%, hydrocortisone in 48.48%, betamethasone valerate in 15.15% and betamethasone dipropionate present in 12.12% cosmetic creams available in Pakistan.

Formulation factors affecting the isomerization rate of betamethasone-17-valerate in a developmental hydrophilic cream – a HPLC and microscopy based stability study

The formulation of betamethasone-17-valerate (BV) into topical medicines presents a significant challenge for the formulation chemist. The substance is susceptible to acid and base catalyzed isomerization in aqueous environments, which results in valerate transesterification from carbon 17 to carbon 21 of the steroid ring system. This acyl migration process is of significant clinical importance since the 21-valerate ester possesses only a fraction of the potency of the 17-valerate parent compound. Isomerization of BV should therefore be reduced to a minimum through design of a suitable drug vehicle. In this study, the effect of varying the concentration of several excipient components on the isomerization rate of betamethasone valerate in a model hydrophilic cream has been investigated. These excipients include the emulsifier macrogolstearylether-20/21, the co-emulsifier cetylstearyl alcohol and the thickening agent hydroxyl propyl methylcellulose. Additionally, the influence of pH, the presence of the antioxidant, alpha-tocopherol, as well as the chelating agent, disodium edetate, on the stability of the formulation have been investigated. Trial drug product formulations, which were designed to investigate the influence of the above-mentioned components/parameters were manufactured and their stability was tested according to current ICH Guidelines. The content, purity and crystalline structure of the active substance in these formulations was analyzed by a combination of HPLC and microscopy techniques. The study demonstrates that the rate of isomerization of betamethasone valerate depends significantly on the concentration of emulsifier used in the cream formulation. At higher concentrations of emulsifier the isomerization proceeds rapidly with significant degradation over a period of weeks, whereas at lower concentrations significant degradation may not be observed, even after several years’ storage. The influence of the emulsifier has been shown to be independent of the pH value of the aqueous phase of the cream. These findings have not been reported in previous literature reports on this topic, which have tended to focus on the influence of pH. The results are likely to be of interest to pharmaceutical chemists working on the formulation of glucocorticoids as well as to local- and hospital pharmacists who carry out the practice of dilution of proprietary corticoid preparations, where the choice of diluent is likely to be critical for ensuring the stability of the diluted product.

Efficacy of betamethasone valerate medicated plaster on painful chronic elbow tendinopathy: a double-blind, randomized, placebo-controlled trial.

to investigate the efficacy and safety of a medicated plaster containing betamethasone valerate (BMV) 2.25 mg in patients with chronic elbow tendinopathy. randomized, double-blind, placebo-controlled study with assignment 2:2:1:1 to BMV medicated plaster applied daily for 12 hours, daily for 24 hours or matched placebo. 62 patients aged ≥18 years with chronic lateral elbow tendinopathy were randomized. The primary efficacy variable was pain reduction (VAS) at day 28. Secondary objectives included summed pain intensity differences (SPID), overall treatment efficacy and tolerability. mean reduction in VAS pain score at day 28 was greater in both BMV medicated plaster groups, -39.35±27.69 mm for BMV12-h and -36.91±32.50 mm for BMV24-h, than with placebo, -20.20±27.32 mm. Considering the adjusted mean decreases, there was a statistically significant difference between BMV12-h and placebo (p=0.0110). Global pain relief (SPID) and overall treatment efficacy were significantly better with BMV. BMV and placebo plasters had similar local tolerability and there were few treatment-related adverse events. BMV plaster was significantly more effective than placebo at reducing pain in patients with chronic elbow tendinopathies. The BMV plaster was safe and well tolerated.

Development and validation of an UHPLC method for the determination of betamethasone valerate in cream, gel, ointment and lotion

An ultra high performance liquid chromatographic method has been developed and validated for the determination of betamethasone valerate (BMV) in topical dermatologic formulations. For the development of the method, response surface methodology based on a three-level full factorial design was used. The eluent composition, the column dimension and the flow rate were chosen as relevant experimental parameters to investigate. The response surface plots revealed an optimum separation by using a RP column (30mm×2mm i.d., 2.2μm particle size), at 30°C; isocratic mobile phase consisting of acetonitrile:water (60:40) at a flow rate of 0.2mLmin−1 and a wavelength set at 254nm. The proposed method was validated for four types of matrices according to ICH guidelines requirements. Dexamethasone acetate (DMA) was used as internal standard. Linearity was studied in the range of 5–200μgmL−1 for BMV in spiked matrix samples. Recoveries were in the range of 95–105% and precision was better than 5% for both analytes, either in cream, gel, ointment, or lotion formulations, when using simple sample preparation. Retention times were 0.95min for DMA and 1.40min for BMV, demonstrating a short method run time. The method was successfully applied for routine analysis of dermatological formulations containing betamethasone valerate.

Treatments for Cutaneous Lichen Planus: A Systematic Review and Meta-Analysis.

Cutaneous lichen planus (CLP) is an inflammatory dermatosis. Its chronic relapsing course and frequently spontaneous regression hamper the assessment of treatment effectiveness. To evaluate the efficacy of available treatment modalities for CLP. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov registry. We performed a systematic review of the current literature. All randomized controlled trials, nonrandomized case-control studies, and cohort studies with more than one treatment arm were included. The primary outcomes were complete response and time to complete response. The secondary outcomes were partial response, relapse, time to relapse, reduction of itch, the adverse event rate, and withdrawal due to adverse events. Sixteen studies met the inclusion criteria, of which 11 were randomized controlled trials. Most trials had a small sample size. In the rare studies in which variants other than generalized or classic lichen planus were included, they could not be analyzed separately. Body-of-evidence quality ranged from very low to moderate. Acitretin, sulfasalazine, and griseofulvin were associated with increased overall response rates in comparison with placebo. Narrow-band ultraviolet B radiation (NBUVB) was more effective than 6 weeks' low-dose prednisolone in achieving a complete response, and prednisolone was more effective than enoxaparin. Hydroxychloroquine was more effective than griseofulvin in achieving an overall response. Betamethasone valerate 0.1% ointment had comparable efficacy to calcipotriol ointment. Methotrexate was effective, with a nonsignificant difference in the complete response rate in comparison with oral betamethasone. In nonrandomized controlled trials, oral psoralen plus ultraviolet A photochemotherapy (PUVA) had comparable efficacy to a PUVA bath and NBUVB. Psoralen plus sunlight exposure (PUVASOL) and betamethasone dipropionate 0.05% cream were effective relative to a short course of oral metronidazole. Several effective treatment options are available for CLP. Further well-designed studies are warranted to investigate the efficacy of topical glucocorticoids-the current first-line therapy-as well as other treatment modalities, and the treatment of different variants of CLP.

Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems

The effect of incorporating the lipidic medium-chain triglyceride (MCT) into polymeric film-forming systems (FFS) for topical drug delivery has been evaluated. First, the in vitro release of betamethasone-17-valerate (BMV), a representative dermatological drug, was determined from FFS comprising either hydrophobic polyacrylate co-polymers, or hydrophilic hydroxypropyl cellulose, with and without MCT. Release was enhanced from both polymers in the presence of MCT. Atomic force microscopy imaging and nanoindentation of FFS with MCT revealed two-phase structured films with softer inclusions (0.5 to 4μm in diameter) surrounded by a more rigid structure. Chemical mapping with Raman micro-spectroscopy showed that MCT was primarily confined to the inclusions within the polymer, which predominated in the surrounding film. BMV was distributed throughout the film but was more concentrated outside the inclusions. Furthermore, while BMV dissolved better into the hydrophobic films, it was more soluble in the MCT inclusions in hydrophilic films, suggesting its increased availability for diffusion from these softer regions of the polymer and explaining the release enhancement observed. Second, ex vivo skin penetration studies clearly revealed that uptake of BMV was higher from hydrophobic FFS than that from the more hydrophilic polymer due, at least in part, to the superior anti-nucleation efficiency of the former. Drug was quickly taken up into the SC from which it then diffused continuously over a sustained period into the lower, viable skin layers. In the presence of MCT, the overall uptake of BMV was increased and provides the basis for further optimisation of FFS as simple, convenient and sustained formulations for topical therapy.

Improvement of inflammatory dermatoses severity and quality of life in patients treated with a betamethasone valerate plaster (LIBERE study)

Background: A ready to use betamethasone valerate 0.1% (BMV) dressing was effective and well-tolerated by patients receiving chronic plaque psoriasis treatment. Objective: Collect data related to BMV dressing used in the context of market authorization. Methods: An observational, prospective study, including 258 patients with a maximum 4-weeks-treatment of inflammatory dermatosis with BMV 2.25 mg plaster was performed. The prescription pattern was described and the disease severity assessed using a Physician Global Assessment (PGA). Patient satisfaction as well as their quality of life (DLQI) were evaluated. Clinical evaluation was performed before and after the treatment. Results: The DLQI scores improved from 10.0 ± 5.4 to 3.5 ± 3.5 points (p < 0.0001) and PGA decreased from 12.5 ± 3.1 to 4.2 ± 3.0 points (p < 0.0001). The highest DLQI and PGA improvement was reported for the eczema group. Subjects reported the test dressing was better than prior therapies with 93.5% very satisfied and 90.4% satisfied. Conclusions: The BMV dressing is well-tolerated and effective in the treatment of inflammatory dermatoses, improving both the objective signs of the disease as well as patients’ quality of life.

Detection of glucocorticoid receptor agonists in effluents from sewage treatment plants in Japan

Glucocorticoids (GCs) are widely used as anti-inflammatory drugs. Our previous study demonstrated that several GCs such as cortisol and dexamethasone (Dex) were frequently detected in effluents collected from Japanese sewage treatment plants (STPs) in 2012. In this study, we used the GC-Responsive Chemical-Activated LUciferase gene eXpression (GR-CALUX) assay to elucidate GC receptor (GR) agonistic activities of ten pure synthetic GCs and selected STP effluents in Japan for assessment of the risks associated with the presence of GR agonists. The tested GCs demonstrated dose-dependent agonistic effects in the GR-CALUX assay and their EC50 values were calculated for estimation of relative potencies (REPs) compared to Dex. The GR agonistic potency was in the rank of: clobetasol propionate>clobetasone butyrate>betamethasone 17-valerate>difluprednate>betamethasone 17,21-dipropionate>Dex>betamethasone>6α-methylprednisolone>prednisolone>cortisol. The GR agonistic activity in STP effluents as measured in Dex-equivalent (Dex-EQ) activities ranged from <3.0–78ngL−1 (median: 29ngL−1, n=50). To evaluate the contribution of the target GCs, theoretical Dex-EQs were calculated by multiplying the concentrations of each GC by its respective REP. Our calculation of Dex-EQ contribution for individual GR agonists indicated that the well-known GCs cortisol and Dex should not be given priority for subsequent in vivo testing, monitoring and removal experiments, but rather the highly potent synthetic GCs clobetasol propionate and betamethasone 17-valerate (REP=28 and 3.1) as well as other unidentified compounds are important GR agonists in STP effluents in Japan.