Topical Betamethasone Valerate As a Prophylactic Agent to Prevent Acute Radiation Dermatitis in Head and Neck Malignancies: A Randomized, Open-Label, Phase 3 Trial.

PURPOSE: We assessed the role of topical betamethasone as a prophylactic agent in patients receiving radiation for head and neck malignancies. METHODS AND MATERIALS: This randomized, open-label, phase 3 trial was completed at a single research institute. Patients receiving curative radiation for head and neck cancer were randomized into 2 groups of 75 patients each by computer-generated permuted block random assignment. Patients in the test arm applied 0.1% topical betamethasone valerate cream once a day, after radiation. Patients in the control arm received best supportive care. The Radiation Therapy Oncology Group acute toxicity grading scale was used to assess radiation dermatitis after every fifth fraction until completion and at 2 weeks after treatment. Primary outcome in both arms was the proportion of patients who developed grade 2 and 3 acute skin reaction. The trial is registered at the Central Trial Registry of India (CTRI/2017/04/008298). RESULTS: Between April 15, 2017, and October 30, 2018,150 patients were randomized into the study, with 75 patients in each arm. Fourteen patients in the test arm and 15 patients in the control arm did not complete the intended treatment. Per the intention-to-treat analysis, 25 of 75 patients (33.3%) and 38 of 75 patients (50.7%) developed grade 2 or greater radiation dermatitis in the test and control arms, respectively (absolute difference, 17.4%; 95% confidence interval, 4%-30%; P = .032). Fifteen of 75 patients (20%) developed grade 3 reactions in the test arm compared with 18 of 75 patients (24%) in the control arm (absolute difference, 4%; 95% confidence interval, 7%-15%; P = .554). CONCLUSION: Although prophylactic use of betamethasone significantly reduced the composite outcome of the proportion of patients developing grade 2 and grade 3 radiation dermatitis, it did not reduce the proportion of patients developing the clinically significant outcome of grade 3 radiation dermatitis.

Labial Adhesion: New Classification and Treatment Protocol.

STUDY OBJECTIVE: To determine the subtypes of labial adhesion (LA) and arrange treatment options accordingly. DESIGN AND SETTING: Patients who presented to our clinic with LA between July 2016 and February 2018 were divided into 4 groups. Location of the adhesion area, thickness of the adhesive tissue, and response to topical steroid (betamethasone valerate 0.1% ointment) therapy were identified as common features. PARTICIPANTS: Seventy-five prepubertal girls. INTERVENTIONS AND MAIN OUTCOME MEASURES: To determine the subtypes of the LA and evaluate the treatment response of patients in each subtype group. RESULTS: LA was divided into 4 subtypes according to their common characteristics. For patients with type I, 2 weeks of topical steroid treatment resulted in complete recovery (100%). For those with type II, 12 (80%) patients had complete response to topical steroid treatment for an average of 3 weeks. Type III and IV patients were completely unresponsive to topical steroid treatment. CONCLUSION: Classification of LA patients into subtypes and determination of treatment on the basis of this classification make a major contribution in planning the treatment of patients, not by trial-and-error, but using a predetermined strategy.

The use of steroid cream for physiologic phimosis in male infants with a history of UTI and normal renal ultrasound is associated with decreased risk of recurrent UTI.

BACKGROUND: An uncircumcised male infant with a history of urinary tract infection (UTI), physiologic phimosis, and a normal renal ultrasound is a common patient referred to pediatric urology clinics. Topical steroid creams have been shown to effectively release physiologic phimosis. OBJECTIVE: The objective of this study was to test the hypothesis that use of steroid cream for physiologic phimosis is associated with a lower UTI recurrence in uncircumcised male infants with normal renal ultrasounds. STUDY DESIGN: Uncircumcised males younger than 12 months referred for a UTI with a normal renal ultrasound were included. A longitudinal data set was created, and recurrent UTIs were identified. The proportion with a recurrent UTI was compared between those who received a prescription for a steroid cream for phimosis and those who did not. The morbidity of the initial and recurrent UTIs was also described. The association of recurrent UTI with vesicoureteral reflux (VUR) was also evaluated. RESULTS: A total of 192 uncircumcised males with a median age of 5.8 months (interquartile range [IQR]: 3.5-7.9 months) were included. Twenty-seven patients were treated with a course of betamethasone valerate 0.1% cream, and 165 were not (Summary Table). There were no significant differences between groups in the frequency of voiding cystourethrogram (VCUG), diagnosis of VUR, or use of continuous prophylactic antibiotics (CAP). During a median follow-up of 8.7 months (IQR: 3.1-17.5 months), none of the patients treated with steroid cream had a recurrent UTI compared with 27 of 165 (16%) patients not treated (P = 0.02). Among the 173 patients whose initial UTI was febrile, recurrent febrile UTIs occurred in no treated patients and 23 of 150 (15%) untreated patients (P = 0.047). DISCUSSION: The results of this study are consistent with those of a previous randomized trial of steroid cream for physiologic phimosis which found lower recurrent UTI in those whose foreskins became retractable. In addition, the results are consistent with the declining incidence of UTIs in uncircumcised males mirroring the natural history of physiologic phimosis resolving. This study is limited by its retrospective nature and non-standardized follow-up. CONCLUSION: The use of steroid cream for physiologic phimosis is associated with a decreased risk of recurrent UTIs in uncircumcised male infants with a normal renal ultrasound. In this group, steroid cream for physiologic phimosis is a well-tolerated and simple alternative to circumcision to potentially decrease risk of recurrent UTI.

Potential of biocompatible polymeric ultra-thin films, nanosheets, as topical and transdermal drug delivery devices.

The aim of the present study was to assess the potential of biocompatible polymeric nanosheets as topical and transdermal drug-delivery devices. Nanosheets are two-dimensional nanostructures with a thickness in the nanometer order, and their extremely large aspect ratios result in unique properties, including high transparency, flexibility, and adhesiveness. Nanosheet formulations containing betamethasone valerate (BV) as a model drug and consisting of poly (L-lactic acid) or poly (lactic-co-glycolic) acid were fabricated through a spin-coating-assisted layer-by-layer method using a water-soluble sacrificial membrane. The fabricated formulations could incorporate and release higher amounts of BV compared with a commercial ointment, and the amounts could be controlled by the polymers used, the amount of BV added, and the use of controlled-release membranes. The presence of BV had a minimal effect on thickness, transparency, adhesiveness, and moisture permeability of nanosheets, permitting their application to any area of skin for a long period of time. Therefore, this biocompatible polymeric nanosheet formulation represents a novel and promising topical and transdermal drug delivery device, which has potential to deliver drugs regardless of the area of skin.

Hyaluronic acid-modified betamethasone encapsulated polymeric nanoparticles: fabrication, characterisation, in vitro release kinetics, and dermal targeting.

Atopic dermatitis (AD) is a chronically relapsing eczematous skin disease characterised by frequent episodes of rashes, severe flares, and inflammation. Till date, there is no absolute therapy for the treatment of AD; however, topical corticosteroids (TCs) are the majorly prescribed class of drugs for the management of AD in both adults and children. Though, topical route is most preferable; however, limited penetration of therapeutics across the startum cornum (SC) is one of the major challenges for scientists. Therefore, the present study was attempted to fabricate a moderate-potency TC, betamethasone valerate (BMV), in the form of chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. To further improve the targeting efficiency of BMV and to potentiate its therapeutic efficacy, the fabricated BMV-CS-NPs were coated with hyaluronic acid (HA). The prepared NPs were characterised for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, loading capacity, crystallinity, thermal behaviour, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimised HA-BMV-CS-NPs exhibited optimum physicochemical characteristics including finest particle size (< 300 ± 28 nm), higher zeta potential (+ 58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that HA-BMV-CS-NPs displayed Fickian diffusion-type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency of BMV was comparatively higher in case of BMV-CS-NPs; however, the amount of drug retained into the epidermis and the dermis was comparatively higher in case of HA-BMV-CS-NPs, compared to BMV-CS-NPs. Conclusively, we anticipate that HA-BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.

Nanoencapsulation of betamethasone valerate using high pressure homogenization-solvent evaporation technique: optimization of formulation and process parameters for efficient dermal targeting.

Betamethsone valerate (BMV), a medium potency topical corticosteroid, is one of the most commonly employed pharmacological agents for the management of atopic dermatitis in both adults and children. Despite having remarkable pharmacological efficacy, these agents have limited clinical implication due to poor penetration across the startum cornum (SC). To mitigate issues related to targeted delivery, stability, and solubility as well as to potentiate therapeutic and clinical implication, the nanodelivery systems have gained remarkable recognition. Therefore, this study was aimed to encapsulate BMV into the chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. The prepared NPs were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, loading capacity, crystallinity, thermal behavior, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimized BMV-CS-NPs exhibited optimum physicochemical characteristics including small particle size (< 250 ± 28 nm), higher zeta potential (+58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that BMV-CS-NPs displayed Fickian-diffusion type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency and the amount of BMV retained into the epidermis and the dermis were comparatively higher in case of BMV-CS-NPs compared to BMV solution. Conclusively, we anticipated that BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.

Simultaneous HPLC Determination of Betamethasone Esters-Containing Mixtures: Analysis of Their Topical Preparations.

Topical pharmaceutical preparations containing betamethasone esters are widely prescribed for treatment of severe inflammatory skin conditions. Some betamethasone esters-containing preparations are formulated with either an antibacterial or an antifungal agent or a vitamin D3 derivative. A fast reversed-phase high-performance liquid chromatography method has been developed for the simultaneous determination of three betamethasone esters-containing binary mixtures along with the excipients of their dosage forms using clobetasone butyrate as internal standard. The first mixture was betamethasone valerate and fusidic acid (Mixture I) with chlorocresol as preservative. The second mixture was betamethasone dipropionate (BTD) and clotrimazole (Mixture II) with benzyl alcohol as preservative. The third mixture was BTD and calcipotriol monohydrate (Mixture III). Optimized chromatographic separation was achieved on a Discovery® C18 (4.6 × 250 mm, 5 µm) column, using water: acetonitrile (35:65, v/v) as mobile phase at flow rate of 1 mL/min with UV detection at 230 nm. The method was validated according to ICH guidelines. The regression coefficients were > 0.999 for all drugs. The method was successfully applied for the determination of the studied drugs in bulk, synthetic mixtures and dosage forms. The developed method is accurate, sensitive, selective and precise and can be used for routine analysis in quality control laboratories.

The use of biodegradable microneedle patches to increase penetration of topical steroid for prurigo nodularis.

BACKGROUND: The stratum corneum is an almost impermeable barrier. Recently, microneedles have been used to increase drug delivery passing the stratum corneum by incorporating the drug within the microneedle or by coating the surface of the microneedle with the drug. OBJECTIVE: This study was performed to investigate whether applying a biodegradable microneedle patch after topical steroid application increases penetration of the steroid in vitro, as well as treatment efficacy in patients with prurigo nodularis. MATERIALS & METHODS: In vitro penetration of topical steroids after biodegradable microneedle patch application was measured using a 3D skin model. To evaluate the treatment efficacy of the combination of biodegradable microneedle and topical steroids, a split-body clinical study was performed. RESULTS: Penetration of topical steroid in the in vitro skin model was significantly greater in the microneedle-applied skin. In a split-body clinical study with prurigo nodularis patients, the area and height of skin lesions decreased after four weeks of treatment on both sides, however, the microneedle patch side exhibited a significantly greater decrease in both area and height, compared to the control side. The pruritus visual analogue scale was also significantly lower on the microneedle side. CONCLUSION: We suggest that simply applying a microneedle patch after topical steroid application could be a useful strategy for treating refractory skin diseases such as prurigo nodularis.

Comparative study of fractional CO2 laser and fractional CO2 laser-assisted drug delivery of topical steroid and topical vitamin C in macular amyloidosis.

Macular amyloidosis (MA) represents a common variant of primary localized cutaneous amyloidosis. It has a characteristic female predominance; none of the treatment modalities described is either curative or uniformly effective in patients with macular amyloidosis. To determine the effect of fractional CO2 laser in macular amyloidosis in comparison to fractional CO2 laser-assisted drug delivery of topical steroids and topical vitamin C, the study includes 10 female patients with cutaneous macular amyloidosis aged between 20 and 62 years. Patients were treated with four sessions of fractional CO2 laser with 4 weeks interval. Laser treatments were performed using fractional CO2 laser with the following parameters (power 18 W, spacing 800 µm, dwell time 600 µs, stacking 3). The lesion is divided into three areas: area 1, treated by fractional laser only; area 2, treated by fractional laser followed by topical corticosteroid application under occlusion for 24 h; and area 3, treated by fractional laser followed by topical vitamin C serum application under occlusion for 24 h. All lesions were examined clinically and histologically before the therapy and 1 month after the end of the therapy to evaluate the degree of improvement. All treated areas show significant decrease in pigmentation score after treatment, significant drop in rippling (P value < 0.016), and improvement of lichenification; as regards the histological improvement, there was a significant decrease of the amyloid amount after treatment. As regards the amyloid amount, results show significant decrease in the amount of amyloid in all of the three treated areas. Area 2 reported the highest decrease in the amyloid amount followed by areas 1 and 3. One patient (10%) was highly satisfied by the treatment, 6 (60%) reported moderate degree of satisfaction, while only 3 (30%) reported mild satisfaction. Minimal complication occurred in the form of post-inflammatory hyperpigmentation in 1 patient. None of the patients suffered pain, ulceration, or infection. Fractional CO2 alone can be used to improve the texture of macular amyloidosis. If used to assist the delivery of topical steroids and topical vitamin C, improvement can be highly increased.

Palm Olein Emulsion: a Novel Vehicle for Topical Drug Delivery of Betamethasone 17-Valerate.

This study aims to investigate the use of palm olein as the oil phase for betamethasone 17-valerate (BV) emulsions. The physicochemical properties of the formulations were characterized. In vitro drug release study was performed with the Hanson Vertical Diffusion Cell System; the samples were quantified with HPLC and the results were compared with commercial products. Optimized emulsion formulations were subjected to stability studies for 3 months at temperatures of 4, 25, and 40°C; the betamethasone 17-valerate content was analyzed using HPLC. The formulations produced mean particle size of 2-4 µm, viscosities of 50-250 mPa.s, and zeta potential between -45 and -68 mV. The rheological analyses showed that the emulsions exhibited pseudoplastic and viscoelastic behavior. The in vitro release of BV from palm olein emulsion through cellulose acetate was 4.5 times higher than that of commercial products and more BV molecules deposited in rat skin. Less than 4% of the drug was degraded in the formulations during the 3-month period when they were subjected to the three different temperatures. These findings indicate that palm olein-in-water emulsion can be an alternative vehicle for topical drug delivery system with superior permeability.

Are the Spanish baseline series markers sufficient to detect contact allergy to corticosteroids in Spain? A GEIDAC prospective study.

BACKGROUND: Corticosteroids are among the most commonly used topical drugs. Contact allergy to these exists, but can be easily missed. Corticosteroid screening markers have been included in the baseline series with the aim of detecting most of the sensitized patients. OBJECTIVES: To assess the prevalence of contact allergy to topical corticosteroids in Spain and examine the usefulness of corticosteroid markers to detect contact allergy to corticosteroids. METHODS: In total, 3699 patients referred to 20 dermatology departments across Spain for patch testing with the baseline series, including budesonide and tixocortol pivalate, were also tested with six supplementary corticosteroids (methylprednisolone aceponate, mometasone furoate, prednicarbate, clobetasol propionate, betamethasone 17-valerate, and betamethasone 17,21-dipropionate). Additionally, 2547 (68.8%) patients were tested with hydrocortisone 17-butyrate. RESULTS: Fifty-four patients showed positive reactions to at least one of all tested corticosteroids (1.46%). Thirty-nine (1.05%) reacted to at least one of the additionally tested corticosteroids; among these, 24 of 39 (61.5%) did not react to any of the corticosteroid allergy screening markers tested. CONCLUSIONS: More than half of the patients who were allergic to the additionally tested corticosteroids were not detected with the corticosteroid allergy markers. An update of the corticosteroid allergy screening markers is encouraged, with consideration of group 3 corticosteroids.

Preclinical Assessment of Steroidal Nanostructured Lipid Carriers Based Gels for Atopic Dermatitis: Optimization and Product Development.

BACKGROUND: Betamethasone Valerate (BV) is a potent topical corticosteroid. Preparation of nanostructured lipid carriers (NLC) involves process parameters optimization and formulations were developed. It is available in several conventional formulations like creams and ointments which have well-known problems of frequent dosing and consequently additional side effects. The aim is to ascertain the probability of NLC as an exclusive carrier for betamethasone valerate topical application with regard to release modulation and improved therapeutic effect. METHOD: Preparation of BVNLC formulations involves rigorous broad range optimization of process parameters viz. selection of lipids, surfactants, formulation technique, stirring time, stirring speed and homogenization cycles. Accordingly, optimized parameters were selected and formulation table was developed. Characterizations of developed NLC comprise particle shape, size, zeta potential, percent drug entrapment, in vitro drug release studies. The optimized NLC formulation was gelled and evaluated for ex vivo permeation studies and preclinical anti-inflammatory testing. RESULTS: The permeation studies revealed that enhancement ratio of BVNLC based gel was 2.59 folds higher as compared to plain BV gel. Release models indicated anomalous (non-fickian) diffusion viz. drug release is controlled by more than one process i.e. superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. Preclinical studies indicated a significant (P < 0.05) extended anti-inflammatory effect and 16.5% inhibition compared to plain gel. CONCLUSION: The outcome of entire characterization advocates that the developed formulation is efficient as once a day dosing in therapy of atopic dermatitis.

Atorvastatin as adjunctive therapy for chronic plaque type psoriasis versus betamethasone valerate alone: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Psoriasis is a T helper 1 cell-mediated chronic inflammation. Statins have been found to have anti-inflammatory and immunomodulatory effects targeting T helper 1 cells and thus, are being investigated as treatments for psoriasis. AIMS: To investigate the efficacy and safety of atorvastatin as adjunctive treatment for mild to moderate chronic plaque psoriasis; and the impact of atorvastatin on quality of life. The study also aimed to correlate the beneficial effects of atorvastatin with its lipid-lowering effects. METHODS: Twenty-eight (19-65 year old) mild-moderate chronic plaque psoriasis patients were randomly assigned to two groups (treatment group: atorvastatin 40 mg OD; control group: placebo OD) and followed up for 6 months. All were allowed to use betamethasone valerate 0.1% ointment twice a day for a maximum of 3 weeks continuous application with 1-week rest periods in between. Primary outcome measures were the mean percentage reduction in Psoriasis Area and Severity Index (PASI) scores and percentage of patients achieving PASI-50. RESULTS: Fourteen patients (treatment: 6, control: 8) completed the trial. Mean reductions in PASI scores between the treatment (2.15 ± 2.17) and control (1.69 ± 2.36) groups were not statistically significant (P = 0.636). Intention-to-treat analysis of PASI-50 showed increased risk of treatment failure with atorvastatin as adjunct but estimates were not significant. Changes in Dermatology Life Quality Index (DLQI) scores (P = 0.214) and high-sensitivity C-reactive protein (P = 0.884) were likewise not statistically significant. Reductions in PASI scores were not linearly correlated with reductions in total cholesterol (P = 0.924), triglycerides (P = 0.274), low-density lipoprotein-cholesterol (P = 0.636), high-density lipoprotein-cholesterol (P = 0.584), or high-sensitivity C-reactive protein levels (P = 0.906). Adverse effects in the treatment group were transient elevated transaminases (n = 1) and mild myalgia (n = 1). LIMITATIONS: A 50% dropout rate was experienced. This remarkably high dropout rate decreases the robustness of the study results. CONCLUSIONS: Although atorvastatin exhibited earlier percentage reduction in PASI scores, it was not able to produce an additional benefit compared to psoriatic patients applying steroid alone.

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

BACKGROUND: Topical 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. OBJECTIVE: This 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. METHODS: AD-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. RESULTS: After 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. CONCLUSION: The 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.

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 and Safety of Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam Compared with Betamethasone 17-Valerate-Medicated Plaster for the Treatment of Psoriasis.

BACKGROUND: Fixed combination calcipotriol as hydrate (Cal) 50 µg/g plus betamethasone as dipropionate (BD) 0.5 mg/g aerosol foam is an alcohol-free treatment for psoriasis. Betamethasone 17-valerate 2.25 mg (BV)-medicated plasters are recommended for treating psoriasis plaques localized in difficult-to-treat (DTT; elbow, knee, anterior face of the tibia) areas. OBJECTIVE: The aim of this study was to compare the efficacy of Cal/BD foam with BV-medicated plaster in patients with plaque psoriasis. METHODS: In this phase IIa, randomized, single-center, investigator-blinded, 4-week study, both Cal/BD foam and BV-medicated plaster were applied once daily to six test sites (three for each treatment). The primary efficacy endpoint was absolute change in total clinical score (TCS; sum of erythema, scaling, and infiltration); secondary endpoints were changes from baseline in each individual clinical score, ultrasonographic changes (total skin and echo-poor band thickness), and safety; and post hoc analysis was change from baseline in TCS on DTT areas. RESULTS: Thirty-five patients were included. Least-squares mean change in TCS from baseline was significantly greater for Cal/BD foam (-5.8) than BV-medicated plaster (-3.7; difference -2.2; 95% confidence interval -2.6 to -1.8; p < 0.001); greater changes for Cal/BD foam were observed from day 8 for each clinical sign. Absolute total skin and echo-poor band thickness change was significantly greater for Cal/BD foam than for BV-medicated plaster (both p < 0.001). Post hoc analyses showed that Cal/BD foam was significantly more effective than BV-medicated plaster on DTT areas after 4 weeks (p < 0.001), and both treatments were well tolerated. CONCLUSION: Cal/BD foam demonstrated superior efficacy versus BV-medicated plasters, including on DTT areas, in patients with plaque psoriasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT02518048.

Corticosteroid transdermal delivery significantly improves arthritis pain and functional disability.

Arthritis is characterized by pain and functional limitation affecting the patients' quality of life. We performed a clinical study to investigate the efficacy of a betamethasone valerate medicated plaster (Betesil) in improving pain and functional disability in patients with arthritis and osteoarthritis. We enrolled 104 patients affected by osteoarthritis (n = 40) or arthritis (n = 64) in different joints. Patients received diclofenac sodium cream (2 g, four times a day) or a 2.25-mg dose of Betesil applied to the painful joint every night before bedtime for 10 days. Pain and functional disability were assessed, by the Visual Analogue Scale (VAS) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores. Redness was assessed by clinical inspection, and edema by the "fovea sign" method. C-reactive protein (CRP) was also measured; CRP can be used to cost-effectively monitor the pharmacological treatment efficacy and is increased during the acute-phase response, returning to physiological values after tissue recovery and functional restoration. All measurements were at baseline and at 10-day follow-up. At 10-day follow-up, a greater improvement in VAS and WOMAC pain and WOMAC stiffness and functional limitation scores from baseline was observed in patients treated with Betesil compared with diclofenac (all p < 0.01). At 10-day follow-up, improvement in redness, edema, and CRP levels from baseline was also greater in patients treated with Betesil compared with diclofenac (all p < 0.01). This study demonstrates the safety and efficacy of transdermal delivery of betamethasone valerate in patients affected by arthritis and osteoarthritis.