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Topical application of the glucocorticoid betamethasone (BM) is a common treatment for inflammatory-related skin diseases, such as psoriasis. However, enhancing its bioavailability remains challenging due to poor skin permeability. Herein, we developed and evaluated hyaluronan-cholesterol (HACH) based nanohydrogel systems (NHs) and NHs-Carbopol formulation for dermal delivery of BM. Various parameters were investigated including particle size, surface charge, encapsulation efficiency, in vitro drug release kinetics and stability. The HACH-based NHs demonstrated high encapsulation efficiency, with apparent solubility improved up to 9-fold, small size (∼190 nm) and good stability at 4 ℃ and during long-term storage. Besides, the NHs-Carbopol formulation exhibited excellent rheological properties and an occlusive effect suitable for cutaneous application. Both in-vitro (using Strat-M® membrane) and ex-vivo (using pig ear skin) permeation studies revealed that these formulations significantly improved skin permeation and drug retention in the deeper layers of the epidermis and dermis, making it advantageous for the topical delivery of BM in psoriasis treatment. Moreover, the NHs system demonstrated potential anti-psoriatic activity by downregulating the proinflammatory cytokines in vitro in human keratinocytes (HaCaT cell line) and in an ex vivo 3D skin tissue model (EpiDerm-FT™)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease that severely impairs patient's life quality and represents significant therapeutic challenge due to its pathophysiology arising from skin barrier dysfunction. Topical corticosteroids, the mainstay treatment for mild to moderate AD, are usually formulated into conventional dosage forms that are impeded by low drug permeation, resulting in high doses with consequent adverse effects, and also lack properties that would strengthen the skin barrier. Herein, we aimed to develop biomimetic lamellar lyotropic liquid crystals (LLCs), offering a novel alternative to conventional AD treatment., Methods: In screening studies, pseudoternary phase diagrams alongside polarized light microscopy (PLM) and viscosity measurements were utilized. Next, the selected LCCs underwent comprehensive characterization via PLM, small-angle X-ray scattering, differential scanning calorimetry, and rheological analysis. Lastly, their performance was evaluated and compared with the commercially available reference medicine in chemical stability study, in vitro permeation testing, in vitro safety assessment using cell proliferation assay, inverted light microscopy, and Raman mapping of keratinocytes, besides gap closure assay performed by live-cell imaging., Results: Formulation (L/T)Ho30, containing the highest amount of lecithin/Tween 80 mixture (21%) and hempseed oil (28%), demonstrated lamellar microstructure with high skin hydration potential and favourable rheological features for skin administration. Moreover, in comparison with the reference medicine, it stood out by providing suitable chemical BD (betamethasone dipropionate) stability, improved 3-fold BD permeation, and excellent biocompatibility with over 85% cell proliferation at all tested concentrations, ensuring keratinocytes' integrity, as well as promoting skin healing with gap closure observed after 36 hours., Conclusion: Unique multi-target drug delivery strategy depicted in newly developed bioinspired lamellar LCCs structurally resembling stratum corneum intercellular lipids, with incorporated BD drug, and composed of multifunctional components that synergistically strengthen skin barrier, was presented here and shows a promising approach for improved AD treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Vitek et al.)

Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis., Competing Interests: Declarations Ethics approval and consent to participate The animal experiments were approved by the Ethics Committee for Experimental Use of Animals of the Shanghai Jiao Tong University School of Medicine (approval code: #SYXK-2013-0050). Consent for publication All authors agree for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This study evaluates the physicochemical compatibility of six active pharmaceutical ingredients (APIs) - 17-a-estradiol, betamethasone, finasteride, melatonin, prednicarbate, and spironolactone - in TrichoFoam™, a foaming vehicle designed for personalized alopecia treatments., Background: Alopecia, a condition impacting around 2% of the global population, can benefit from more effective and patient-friendly treatments. TrichoFoam™ represents a personalized medicine approach that utilizes a foam base to enhance the delivery and efficacy of topical treatments., Methods: The physicochemical compatibility was assessed using High-Performance Liquid Chromatography (HPLC) and Ultra-High Performance Liquid Chromatography (UHPLC) to ensure that the APIs remain stable and effective within TrichoFoam™. Products evaluated were: 17-a-estradiol 0.025% - 0.05%, betamethasone 0.1% - 0.2%, finasteride 0.01% - 0.25%, melatonin 0.05% - 0.5%, prednicarbate 0.1%, and spironolactone 1.0%. Forced degradation studies and stability-indicating analyses were conducted to determine the APIs' stability under various conditions., Results: The beyond-use dates found were: 17-a-estradiol 0.025% = 120 days; 17-a-estradiol 0.05%= 14 days; Betamethasone 17-valerate 0.1% = 180 days; Betamethasone 17-valerate 0.2% = 120 days; Finasteride 0.01% to 0.25% = 120 days; Melatonin 0.05% to 0.5%= 60 days; Prednicarbate 0.1% = 60 days; Spironolactone 1.0% = 14 days. The APIs demonstrated satisfactory compatibility with TrichoFoam™, with no significant chemical interactions or stability issues observed. Stability studies showed that the APIs maintained their efficacy within the foam base over time, with acceptable recovery percentages., Conclusion: This study can further support the use of TrichoFoam™ as a viable vehicle for delivering multiple APIs in a personalized alopecia treatment regimen. The compatibility and stability of the APIs within this formulation offer a promising advancement in tailored alopecia treatments, potentially improving patient adherence and therapeutic outcomes., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Epimers can show different biological activities and different pharmacological behaviors; therefore, their separation and analysis are crucial in the drug development process. Due to their similar chemical and physical properties, separation of epimers is challenging. This study demonstrates the application of cyclic ion mobility-mass spectrometry to separate, identify, and quantify dexamethasone and betamethasone in a binary mixture. Cyclic IMS separation of the isolated protonated dimer resulted in three peaks: dexamethasone homodimer, betamethasone homodimer, and their heterodimer. Besides providing improved separation over the protonated monomer, the presence of a heterodimer peak provides additional confirmation of an isomeric mixture. We identified the dexamethasone and betamethasone homodimer peaks by infusing pure solutions of each epimer and measuring each pure homodimer's arrival time. The measured peak areas indicated that the heterodimer is formed at twice the rate of each homodimer and that dexamethasone and betamethasone contribute equally to the heterodimer signal. Using this observation, we could accurately calculate the relative concentrations of each epimer by adding half of the heterodimer peak area to each homodimer peak area. These findings enable the identification and quantification of dexamethasone and betamethasone based on the arrival time distributions of their protonated dimers. This is the first demonstration of accurate relative quantification of epimers by separating charged dimers in the gas phase.

Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE 2 ). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases., (© 2024 Wiley‐VCH GmbH.)

The aim of this work was the development of a film-forming formulation (FFF) for the topical treatment of psoriasis that shows an increased substantivity compared to conventional semi-solid dosage forms. The developed formulation is an oleogel. It is based on a combination of castor oil and medium chain triglycerides, and the oil-soluble film former MP-30 (Croda GmbH, Nettetal, Germany), a polyamide that upon mixing with a polar oil entraps the oil und thus substantially increases the viscosity of the formulation up to a semisolid state. Betamethasone dipropionate (BDP) and calcipotriole (CA) were used as active pharmaceutical ingredients (APIs). Oleogels of different compositions were evaluated regarding substantivity, rheological properties, ex-vivo penetration into the skin and ex-vivo permeation through the skin. Marketed products were used as controls. It was found that the amount of betamethasone dipropionate penetrating and permeating into and through the skin from the film-forming formulation is at an intermediate value compared to the marketed products. The substantivity of the developed formulation is described by an amount of 57.7 % formulation that remains on the skin surface and is thus significantly higher compared to the marketed products. In the film forming formulation, the proportion of API penetrating the skin remains the same when the skin repetitively brought in contact with a piece of textile during the penetration experiment. In contrast with the in-market formulations tested, this proportion was reduced by up to 97 %. As a result, the developed formulations can lead to an increased patient compliance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Antenatal glucocorticoids (GCs) reduce respiratory distress syndrome (RDS) in preterm infants and are associated with reduced lung liquid content. Our aim was to assess whether airway gene expression of mediators of pulmonary epithelial sodium and liquid absorption, and further, respiratory morbidity, associate with cord blood GC concentrations., Methods: The study included 64 infants delivered <32 weeks gestation. Cortisol and betamethasone in umbilical cord blood were quantified with liquid chromatography-tandem mass spectrometry. The total GC concentration was calculated. Gene expression of the epithelial sodium channel (ENaC), Na,K-ATPase, and serum- and GC-inducible kinase 1 at <2 h and at 1 day postnatally in nasal epithelial cell samples was quantified with reverse transcription-polymerase chain reaction. The mean oxygen supplementation during the first 72 h was calculated., Results: Concentrations of cord blood betamethasone and total GC were significantly lower in infants with RDS and correlated with mean oxygen supplementation. Expression of αENaC and α1- and β1Na,K-ATPase at <2 h correlated with betamethasone and total GC concentrations. Expression of Na,K-ATPase was lower in infants with RDS., Conclusion: Enhancement of lung liquid absorption via increased expression of sodium transporters may contribute to the beneficial pulmonary effects of antenatal GCs., Impact: RDS is related to lower umbilical cord blood GC concentrations and lower airway expression of sodium transporters. In addition to the timing of antenatal GC treatment, resulting concentrations may be of importance in preventing RDS. Induction of sodium transport may be a factor contributing to the pulmonary response to antenatal GCs.

Corticosteroids were used normally as anti-inflammatory drugs. However, in some area certain corticosteroids might be illegally used as growth promoting agent in feed, and as prohibited doping substances in game and sport for human or/and animal performance-enhancing. Synthesized structural similar corticosteroids were popular in black market because they can pass routine drug screening. In this study two new artificial synthesized corticosteroids were found in claimed hydrolyzed wheat product. Liquid chromatography coupled with high resolution mass spectrometry (HRMS, Orbitrap) was applied to separate and elucidate the corticosteroids in the sample. Two unknown peaks with optical spectra similar to corticosteroids were first screened out at the beginning, and then their accurate molecular weight (M + H + ) m/z 533.29059 and m/z 603.33289 were detected by HRMS. Element formulas of unknowns were calculated by the accurate mass and isotopes abundance. Structures were proposed by their fragment ions at high energy collision dissociation (HCD, 10 eV) and compared with candidate standard compounds. The two unknowns shared similar molecular skeleton with steroid core structure and presented man made fluorine element in their molecule. As the results, the unknowns in the sample were artificial synthesized, and the sample product was not a real food. The detected corticosteroids were also synthesized as reference compounds for conformation. Two new corticosteroids named betamethasone dibutyrate and betamethasone tributyrate were found and first time reported in this work. The legality of structural similar/modified corticosteroids were blurry and their safety were unverified. The confirmed identifications of two new found corticosteroids, and their mass spectra were provided in this paper for the reference of drug detection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric materials are not mechanically stable enough, and have high rates of biodegradation. Thus, synthetic materials such as gellan gum can be used to produce composite structures with biological signals to promote tissue-specific interactions while providing the desired mechanical properties. In this work, we aimed to produce hydrogels of tyramine-modified gellan gum with silk fibroin (Ty-GG/SF) via horseradish peroxidase (HRP), with encapsulated betamethasone, to improve the biocompatibility and mechanical properties, and further increase therapeutic efficacy to treat rheumatoid arthritis (RA). The Ty-GG/SF hydrogels presented a β-sheet secondary structure, with gelation time around 2-5 min, good resistance to enzymatic degradation, a suitable injectability profile, viscoelastic capacity with a significant solid component and a betamethasone-controlled release profile over time. In vitro studies showed that Ty-GG/SF hydrogels did not produce a deleterious effect on cellular metabolic activity, morphology or proliferation. Furthermore, Ty-GG/SF hydrogels with encapsulated betamethasone revealed greater therapeutic efficacy than the drug applied alone. Therefore, this strategy can provide an improvement in therapeutic efficacy when compared to the traditional use of drugs for the treatment of rheumatoid arthritis.

Background: Epidural steroid injection (ESI) is a common practice for pain treatment since 1953. In 2014, the FDA issued a warning about ESI. Studies have focused on the effect of the particle size and their ability to generate harmful aggregates. Although steroid aggregates provide longer times for reabsorption, therefore a longer anti-inflammatory effect, they are potentially harmful to the central nervous system via embolic mechanisms.Previous studies have established that steroidal aggregates with asizes over 100 mu m are potentially able to occlude blood vessels. Studies by Tiso et al and Benzon et al addressed the role of steroids on CNS adverse events, with similar outcomes. The main difference was on the role of aggregates with a size over 100 mu m, which Benzon et al. attributed to the ability of certain steroid preparations to rapidly precipitate and form large aggregates., Objectives: Studying the effect of the time elapsed between mixing the steroid preparation and injection on the number and size of aggregates with sizes above 100 mu m., Study Design: Original study in basic science., Setting: Basic scienceMETHODS: Steroids evaluated are commonly used in Spain for ESI: betamethasone, triamcinolone, and dexamethasone. The size and number of the aggregates was determined for undiluted commercial steroid preparations in the usual amount for a single and double dosage used for ESI.Samples were examined with a Leica TCS-SP2 microscope at the first, the fifth and the 30th minute after shaking the preparations. Aggregates observed in the different preparations were manually counted and grouped in the following size range: 0-20, 20-50, 50-100, 100-300, 300-500 and > 500 mu m.Statistical analysis was carried out using the R software. Nonparametric techniques were used in the comparison of aggregate size. Global comparison of the groups using the Kruskal-Wallis test and post-hoc comparisons using the Wilcoxon test, adjusting P-values by the Holm method for multiple comparisonsRESULTS: Aggregates present in triamcinolone and betamethasone samples were statistically larger than in dexamethasone samples. Triamcinolone suspensions produced significantly larger aggregates than betamethasone five minutes after mixing. Triamcinolone preparations produced greater particle aggregates (> 500 mu m), which were not present in dexamethasone and betamethasone preparations., Limitations: Study how the human internal factors like blood elements and spinal fluid could interact with steroids and influence the size of the aggregates formed., Conclusions: This study demonstrates that the size of the particles injected depends on the type of steroid and the time allowed between mixing and injecting. The results demonstrate that waiting longer than 5 minutes between mixing and injecting can predispose the formation of potentially harmful aggregates in triamcinolone and betamethasone samples. The presence of greater particle aggregates (> 500 mu m) may occlude some important vessels and arteries with serious adverse results. Vigorous shaking of the injectable could prevent such events., Key Words: Epidural steroid injection, triamcinolone, betamethasone, dexamethasone, steroid aggregates.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT., Results: Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis., Conclusions: Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.

Mass spectral analysis of dexamethasone and betamethasone reveal intense signals at m/z 373.19994 (using a Thermo Q Exactive high-resolution mass spectrometer coupled with Dionex UltiMate 3000 UHPLC + operated in the positive ion mode), matching the signal of meprednisone, the 11-oxo version of methylprednisolone, along with its parent signal; possibly due to dehydrohalogenation of these drugs at MS. The parent mass of meprednisone is exactly same as that of dehydrohalogenated mass of dexamethasone and betamethasone; and are co-eluting, displaying same mass spectra. Specifically when they are administered together, identifying meprednisone (a drug for which there is zero tolerance in some regions of the world), is a great challenge with currently available techniques because it could be easily mistaken for dexamethasone or betamethasone, drugs allowed at certain threshold limits for therapeutic considerations. False negative results could be obtained in conventional reverse-phase chromatography and are liable to be abused; hence, establishing "zero tolerance" limits for these compounds often proves ineffective. In this paper, present an effective and reliable analytical method for simultaneously separating and identifying dexamethasone, betamethasone and meprednisone in equine urine and plasma using chiral liquid chromatography-electrospray ionization-mass spectrometry. From the various columns screened, the Lux i-Cellulose-5 chiral column produced high-quality results with extremely good separation. During this study, it is quite evident that dehydrohalogenation occurs only in the mass ionization source; the compounds are very stable in-vivo/in-vitro and do not break down either on-column or during sample preparation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: For the first time, the anti-inflammatory drug betamethasone is investigated for its inhibitory activity against lipase., Objective: This work aims to demonstrate the in vitro and in silico inhibitory effect of the anti-inflammatory drug betamethasone on the enzymatic activity of two lipases., Methods: In vitro study using p-nitrophenyllaurate as lipase substrate is used to determine inhibition potency. Molecular Docking is performed using the Autodock Vina for drug molecule and two enzymes Candida rugosa lipase and human pancreatic lipase., Results: Betamethasone represents a moderate inhibition effect with a value of IC50 of 0.36±0.01 mg/ml. Molecular docking allowed us to understand inhibitory - enzyme interactions and to confirm in vitro obtained results., Conclusion: These experiments showed that betamethasone can be used in the treatment of diseases related to lipase activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

There is evidence that encapsulating glucocorticoids into nucleic acid-containing nanoparticles reduces the inflammatory toxicities of the nanoparticles. Herein, using betamethasone acetate (BA), a glucocorticoid, and a solid lipid nanoparticle formulation of siRNA, we confirmed that coencapsulating BA into the siRNA solid lipid nanoparticles significantly reduced the proinflammatory activity of the siRNA nanoparticles in a mouse model. Using TNF-α siRNA, we then showed that the BA and TNF-α siRNA coencapsulated into the solid lipid nanoparticles acted as a dual anti-inflammatory and synergistically reduced TNF-α release by mouse macrophages in culture following stimulation with lipopolysaccharide, as compared to solid lipid nanoparticles encapsulated with TNF-α siRNA or BA alone. Importantly, upon studying the effect of the ratio of BA and TNF-α siRNA on the proinflammatory activity of the resultant nanoparticles, we identified that BA and TNF-α siRNA coencapsulated solid lipid nanoparticles prepared with a BA to TNF-α siRNA weight ratio of 2:1 induced the lowest proinflammatory cytokine production by macrophages in culture. This result was in comparison to nanoparticles prepared with BA to TNF-α siRNA ratios both higher and lower than 2:1 (i.e., 4:1, 1:1, and 0.5:1) and is likely due to differences in molecular interactions among the various components in the BA and TNF-α-siRNA coencapsulated solid lipid nanoparticles at these ratios. Encapsulating glucocorticoids into siRNA-nanoparticles represents a viable strategy to reduce the proinflammatory activity of the nanoparticles; however, the ratio of the glucocorticoid to siRNA in the nanoparticles requires optimization.

This study was performed to achieve two primary goals: First, a microemulsion containing betamethasone dipropionate was optimized using the quality by design approach. Second, a hydrogel-containing microemulsion was developed using cellulose derivatives, and its anti-inflammatory and skin irritation effects were evaluated. Face-centered central composite design was used to investigate the impacts of two independent variables (oleic acid and ratio of surfactant to cosolvent, S/CoS) on three dependent variables (skin deposition, flux of BMD, and microemulsion droplet size). The microemulsion including oleic acid at a low level (coded with -1) and S/CoS at a high level (coded with +1) was considered optimal since it was the most effective in terms of skin deposition and flux of BMD. Different cellulose derivatives (HPMC E6, HEC, NaCMC, and CMC) were screened to prepare a hydrogel-containing microemulsion based on four properties: flux and skin deposition of BMD, hydration of stratum corneum, and rheological properties of hydrogel-containing microemulsion (ME-hydrogel). The anti-inflammatory effect and flux of BMD from optimal ME-hydrogel with carboxymethyl cellulose as the hydrogel-forming agent were then compared to those of the hydrogel-containing solid lipid nanoparticles (SLN-hydrogel) and nanostructure lipid carriers (NLC-hydrogel). The percentage of edema inhibition declined proportionally with flux of BMD in the following order: ME-hydrogel (44.56 ± 8.08%) > NLC-hydrogel (35.93 ± 7.22%) > SLN-hydrogel (25.68 ± 9.05%)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In our study, a method for the determination for tazarotene and betamethasone dipropionate in human tissue-engineered skin was established. Tazarotene gel, betamethasone dipropionate cream or a combination cream was administered to the skin. Then the skin was taken off at 0.25, 0.75, 1.75, 3, 5, 8, 12, 24, 36, 48 h time points after the residual drug was removed. The concentrations of tazarotene, betamethasone dipropionate and their major metabolites in skin were determined by LC-MS. Tazarotene and tazarotenic acid were detected in the concentration range of 2-200 μg/mL with an LLOQ of 2 μg/mL. Betamethasone dipropionate was detected in the concentration range 0.5-300 μg/mL with an LLOQ of 0.5 μg/mL, and betamethasone was detected at 2-200 μg/mL with an LLOQ of 2 μg/mL. The intra- and inter-day precisions of the four analytes in the skin homogenate were all <15% (RSD, %). The results showed that tazarotene could be metabolized to tazarotenic acid and betamethasone dipropionate could be metabolized to betamethasone in tissue-engineered skin. The results also revealed that this method was suitable for the simultaneous determination of tazarotene, betamethasone dipropionate and their metabolites in tissue-engineered skin., (© 2019 John Wiley & Sons, Ltd.)

Chitosan nanoparticles and chitosan beads were synthesized through the ionic gelation procedure in which sodium citrate was used as the cross-linking agent. The prepared nanoparticles were characterized by using transmission electron microscopy (TEM), X-ray diffraction (XRD), zeta potential, and Fourier transform infrared (FT-IR) spectroscopy. The synthesized nanoparticles and beads were examined as drug carriers for controlled release of two important drugs including betamethasone and tetracycline. For this purpose, various properties such as swelling behavior, loading capacity, encapsulation efficiency, and release degree of the particles were obtained. The effect of pH on the aforementioned parameters was also studied. The results indicated that the amount of drug released from chitosan nanoparticles is lower than that released from chitosan beads. It was also found that the release degree for both of the drugs at the pH of 4.8 is much larger than that at the pH of 7.4., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The partitioning of active pharmaceutical ingredients (API) in emulsions is influenced by various factors, such as composition of the phases, emulsifier type and concentration, and temperature. Therefore, the chemical stability of the API can be influenced by its partitioning into the aqueous phase as degradation is typically facilitated in water. With increasing emulsifier concentration from 0.15% to 5.0%, more betamethasone dipropionate (BDP) was solubilized in polysorbate 80 micelles leading to a small, but increased fraction of BDP exposed to the aqueous phase along with preferential partitioning of BDP to the aqueous phase and thus increased degradation. Similarly, by enhancing solubility and partitioning to the aqueous phase, the addition of polyethylene glycol 400 also led to increased BDP degradation. Due to pH dependent degradation of BDP, increasing emulsifier concentrations resulted in a more pronounced degradation of BDP at pH 8, which is beyond the stability optimum, whereas at pH 5 the API was sufficiently stable and no differences in concentration were detected within 12 weeks even under accelerated conditions. No significant differences were seen with the varying emulsifier concentrations regarding ex vivo skin penetration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Two chromatographic methods were developed, optimized and validated for simultaneous determination of calcipotriol monohydrate (CPM) and betamethasone dipropionate (BMD) in the presence of two dosage form additives named; butylated hydroxytoluene (BHT) and alpha-tocopherol (TOCO). The proposed methods were accurate, sensitive and specific. The first method based on using aluminum thin-layer chromatographic plates precoated with silica gel GF254 as a stationary phase and chloroform-ethyl acetate-toluene (5:5:3, by volume) as a developing system. This was followed by densitometric measurement of the separated bands at 264 nm. Whereas the second method is RP-HPLC where OnyxMonolithic C18® column was used with a gradient profile using methanol, water and acetic acid at flow rate 2.0 mL min-1. Detection was carried out at 264 nm. The methods were validated according to ICH guidelines. The specificity of the developed methods was investigated by analyzing the pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by the official methods, showing no significant difference with respect to accuracy and precision at P = 0.05., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Betamethasone dipropionate is a highly effective corticosteroid anti-inflammatory. However, the main drawback of its topical use is the limited skin penetration into deeper skin layers. Also, its systemic use has shown many side effects., Objective: The goal of this research was to formulate betamethasone dipropionate in nanostructured lipid carriers (NLC) formulae that contain oleic acid to aid its penetration to deeper skin layers and to aid absorption to local regions upon topical application., Methods: NLC formulae were prepared by high shear homogenization then sonication. Formulae were characterized for their particle size, size distribution, electric potential, occlusion factor, entrapment efficiency, drug loading, transmission electron microscopy, in vitro drug release, and ex vivo skin penetration. Compatibility of ingredients with drug was tested using differential scanning calorimetry. Formulae were shown to have appropriate characteristics. NLC formulae were superior to traditional topical formulation in drug release., Results: Upon testing ex vivo skin penetration, betamethasone dipropionate prepared in NLC formulae was shown to penetrate more efficiently into skin layers than when formulated as a traditional cream. NLC formulation that contained higher percentage of oleic acid showed higher penetration and higher amount of drug to pass through skin., Conclusion: In general, NLC with lower oleic acid percentage was shown to deliver betamethasone dipropionate more efficiently into deeper skin layers while that of a higher oleic acid percentage was shown to deliver the drug more efficiently into deeper skin layers and through the skin, transdermally., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Betamethasone butyrate propionate ointment (BBP O ) is mainly used for adult patients in dermatology and is often prescribed as a mixture containing a base or moisturizing cream for various reasons. However, in the case of a moisturizing cream, since this formulation is composed of various ingredients, a physical change is expected to occur by mixing it with an ointment. Therefore, in the present study, the physical stability of a mixture of four BBP O formulations and heparinoid oily cream (HP OC ) was examined. Layer separation was observed in all mixtures following centrifugation. The near-infrared (NIR) measurement showed a peak at 5200 cm -1 on the lower layer side, which strongly suggests the presence of water. The peak at 5200 cm -1 in the middle layer was hardly observed in the mixtures of two BBP O generic formulations and HP OC , thus suggesting that the separation was more advanced in those mixtures than in the others. These two mixtures separated into a semisolid layer (upper side) and a liquid layer (lower side) after 3 h of storage at 37 °C. The NIR measurement of each layer revealed that most of the semisolid layer was oil while the liquid layer was water. Furthermore, backscattered light measurements were conducted to monitor the behavior of the mixture's layer separation. An evaluation using model formulations revealed that the layer separation of the mixtures was due to the propylene glycol (PG) and surfactant content of the two generic BBP O formulations. Thus, these findings suggest that excipients need to be considered in selecting formulations for mixtures of skin preparations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Topical active vitamin D3 application alone or in combination with topical steroid application is widely used to treat psoriasis. In Japan, combined calcipotriol hydrate/betamethasone dipropionate ointment has been used for patients with psoriasis vulgaris since September 2014. Current evidence regarding the incidence of hypercalcemia due to the use of this combination product, however, is insufficient. We evaluated the incidence of hypercalcemia following combined calcipotriol hydrate/betamethasone dipropionate ointment in patients with severe psoriasis vulgaris., Methods: Japanese patients (n = 22) with extensive plaque psoriasis (body surface area: 20-30%) applied the combined calcipotriol hydrate/betamethasone dipropionate ointment once daily for 8 weeks, and their serum Ca concentrations were measured periodically., Results: The mean serum Ca concentration changed only marginally, from 9.04 ± 0.34 mg/dL before treatment to 9.08 ± 0.39 mg/dL after 8 weeks of treatment. None of the patients had an elevated serum Ca concentration throughout the study. No cases of hypercalcemia were reported as an adverse event. No correlation was detected between the amount of the combined calcipotriol hydrate/betamethasone dipropionate ointment applied and changes in the serum Ca concentration., Conclusion: The incidence of hypercalcemia due to topical application of a combined calcipotriol hydrate/betamethasone dipropionate ointment is low in Japanese patients with severe psoriasis vulgaris.

Objective: To assess the effectiveness and safety of combining calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam with biologic therapies for patients with plaque psoriasis who have not obtained an adequate response with biologic therapy., Methods: This was a prospective, open-label, single-arm study of patients with chronic plaque-type psoriasis (body surface area [BSA] ≤5%) who were being treated with biologic agents for ≥24 weeks. All patients received once-daily Cal/BD foam for 4 weeks, followed by twice-weekly use on consecutive days for 12 weeks (maintenance regimen). The end points were assessed at weeks 4 and 16, and included the Physician's Global Assessment (PGA), BSA, PGA×BSA, Dermatology Life Quality Index (DLQI), and Treatment Satisfaction Questionnaire for Medication (TSQM)-9. Safety evaluations included assessments of local skin reactions and adverse events (AEs)., Results: Enrolled were 25 patients (18 men and 7 women; mean age, 53 ± 11 years). Patients had significant disease activity despite being on stable biologic therapy (median values: BSA, 3%; PGA, 3; PGA×BSA, 8). At weeks 4 and 16 versus baseline, adjunctive therapy with Cal/BD foam significantly improved PGA score (1 vs 1 vs 3; P less than .01), BSA involvement (1% vs 1% vs 3%; P less than .01), and PGA×BSA measure (1 vs 1 vs 8; P less than .01). Most patients achieved treat-to-target criteria for BSA ≤1% and PGA ≤1 at week 4 (both 76%) and week 16 (both 68%) versus 12% and 4%, respectively, at baseline. Quality of life was improved at both weeks 4 and 16, with high treatment satisfaction. Overall, adjunctive Cal/BD foam was safe and well-tolerated, with no serious AEs., Conclusions: Adjunctive therapy with Cal/BD foam was associated with an improvement of every measure of disease activity in patients with inadequate response to biologics, an effect that was maintained throughout the study. The majority of patients achieved treat-to-target goals. J Drugs Dermatol. 2018;17(8):845-850.

Corticosteroids are widely used in topical formulations such as creams (aqueous) and ointments (non-aqueous). The generally used corticosteroids show large molecular resemblance, where especially the 20-keto-21-hydroxyl group bound to the 17 carbon is important for their chemical stability. Oxidation in both aqueous and non-aqueous environment occurs for triamcinolone acetonide (TCA), hydrocortisone (HC) and desoximethasone (DS). Besides the 20-keto-21-hydroxyl group, TCA, HC and DS have different other moieties attached to the same C17. These moieties are shown to influence not only the type of degradation product formed but also the degradation kinetics. Seven degradation products are found in total and a degradation mechanism is proposed. Furthermore the transesterfication of betamethasone-17-valerate to betamethasone-21-valerate is shown to occur both in aqueous and non-aqueous environment. Finally, a comprehensive scheme of degradation pathways is presented that is applicable for both aqueous and non-aqueous formulations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Activated macrophages play a key role in the development and maintenance of inflammatory diseases such as atherosclerosis, lupus, psoriasis, rheumatoid arthritis, ulcerative colitis, and many others. These activated macrophages, but not resting or quiescent macrophages highly up-regulate folate receptor beta (FR-β). This differential expression of FR-β provides a mechanism to selectively deliver imaging and therapeutic agents utilizing folate as a targeting molecule. In an effort to determine whether inflammatory diseases can be targeted utilizing a folate-linked nanosize carrier, a PEG-coated liposome was prepared that incorporated a folate conjugated PEG that also could transport imaging or therapeutic cargo. We demonstrate that these folate-liposomes specifically bind to folate receptor positive cells and accumulate at sites of inflammation in mouse models of colitis and atherosclerosis. These two animal models show that folate-targeted liposomes could be successfully utilized to deliver fluorescent molecules and an anti-inflammatory drug (betamethasone) for diagnostic and therapeutic applications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives and Methods: Topical therapy is the first-line treatment in mild and moderate psoriasis. We performed a real-life study on topical therapies in psoriasis and observed a variation in the amounts of ointment patients applied during the study., Results: A statistically significant correlation was found between gender and the total amount of ointment used: women used more than men (p = .020). Also, heavier patients tended to use less ointment (p = .038)., Conclusions: We look forward to seeing whether the current pressure to improve psoriasis treatment leads to more patients receiving systemic therapies or to better adherence to, and persistence with, topical therapies.

Aim: We compared the performances of two different commercial products both based on betamethasone and an antibiotic but using different pharmaceutical vehicles: a polymer and lipid-enriched cream and a conventional oil-in-water emulsion., Methodology: Evaluation was conducted on a reconstructed human epidermis model. Moreover, skin barrier properties and cutaneous hydration of the two vehicles were evaluated on 20 human healthy volunteers., Results: Overall, the polymer and lipid-enriched formulation works as a film-forming product that retains the therapeutic agent for a long time, ensuring its penetration and absorption through the skin, and promoting skin hydration., Conclusion: The above characteristics are useful in the clinical setting, especially in the context of eczematous diseases with a strong xerotic component.

A chiral biosensing platform was developed using betamethasone (BMZ) as chiral recognition element through multilayered electrochemical deposition of BMZ, overoxidized polypyrrole, and nanosheets of graphene (OPPy-BMZ/GR), for enantio-recognition of mandelic acid (MA) enantiomers. The deposited film was characterized by scanning electron microscopy, differential pulse voltammetry, cyclic voltammetry, and electrochemical impedance spectroscopy. It was shown that the chiral sensing platform can discriminate R- and S-MA differential pulse voltammetry signals, at the voltages of 1.35 and 1.33 V (vs Ag/AgCl), respectively. To tackle the problem of highly overlapping peaks of these enantiomers, the partial least squares (PLS) regression and genetic algorithm-PLS (GA-PLS) were used for simultaneous quantification of MA enantiomers. Generally, variable selection by genetic algorithm provided an improvement in prediction results when compared to full-voltammogram PLS. Good analytical performances were obtained despite the inherent complexity of the simultaneous determination., (Copyright © 2017 John Wiley & Sons, Ltd.)

Purpose: To evaluate and compare the clinical efficacy, dermoscopic results and safety of triamcinolone acetonide (TA) and betamethasone dipropionate (BD) injections at different concentrations in localized scalp and beard alopecia., Methods: Intralesional injection of BD or TA in three different dilutions; 1/4, 1/8, 1/12 (BD1, BD2, BD3, TA1, TA2, TA3) and Saline (control) was randomly applied to a total of 231 alopecia patches in 83 patients every four weeks in a maximum of six sessions until a hair regrowth score of 4 was achieved. The number of required sessions, sixth-month hair regrowth scores, treatment success rates and dermoscopic data were investigated., Results: The mean number of required sessions were similar and significantly lower in BD1 and TA1 being 4.21 ± 1.12 and 3.74 ± 0.99, respectively. Dermoscopic examinations revealed similar terminal hair growth rations in Saline (30.3%), BD1 (44.4%) and TA1 (42.9%). However, sixth-month hair regrowth scores, overall treatment success rates and percentage of terminal hair regrowth were similar in BD1 and TA1. However, adverse effects were more common in TA groups (24.3%) than in BD groups (10.6%) at the sixth month., Conclusions: BD ¼ dilution (1.25 mg/dL) seems best corticosteroid for intralesional injection in the treatment of localized alopecia areata in adults.

The use of corticosteroids, such as betamethasone, in performance horses is tightly regulated. The objective of the current study was to describe the plasma pharmacokinetics of betamethasone as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (9 mg) of a betamethasone sodium phosphate and betamethasone acetate injectable suspension into the right antebrachiocarpal joint. Blood, urine, and synovial fluid samples were collected prior to and at various times up to 21 days post drug administration. All samples were analyzed using tandem liquid chromatography-mass spectrometry. Plasma data were analyzed using compartmental pharmacokinetic modeling. Maximum measured plasma betamethasone concentrations were 3.97 ± 0.23 ng/mL at 1.45 ± 0.20 h. The plasma elimination half-life was 7.48 ± 0.39 h. Betamethasone concentrations were below the limit of detection in all horses by 96 h and 7 days in plasma and urine, respectively. Betamethasone fell below the limit of detection in the right antebrachiocarpal joint between 14 and 21 days. Results of this study provide information that can be used to regulate the use of intra-articular betamethasone in the horse. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Glucocorticoids (GC) are widely used to treat acute relapses in multiple sclerosis (MS) patients, but their application is accompanied by side effects due to their broad spectrum of action. Here, we report on the therapeutic option to apply GC via inorganic-organic hybrid nanoparticles (IOH-NP) with the composition [ZrO] 2+ [(BMP) 0.9 (FMN) 0.1 ] 2- (designated BMP-NP with BMP: betamethasone phosphate; FMN: flavinmononucleotide). We found that these BMP-NP have an increased cell type-specificity compared to free GC while retaining full therapeutic efficacy in a mouse model of MS. BMP-NP were preferentially taken up by phagocytic cells and modulated macrophages in vivo more efficiently than T cells. When GC were applied in the form of BMP-NP, treatment of neuroinflammatory disease in mice exclusively depended on the control of macrophage function whereas effects on T cells and brain endothelial cells were dispensable for therapeutic efficacy. Importantly, BMP-NP were not only active in mice but also showed strong activity towards monocytes isolated from healthy human volunteers. We conclude that application of GC via IOH-NP has the potential to improve MS therapy in the future., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This study involved the preparation and evaluation of buccal-mucoadhesive microparticles/discs of bethamethasone disodium phosphate (BDSP). The microparticles were prepared using the emulsion solvent diffusion method. Microparticles were prepared and characterized by encapsulation efficiency particle size, Fourier Transform Infra Red (FTIR) spectrums, Differential Scanning Calorimetric (DSC) thermograms and mucoadhesive properties. FTIR studies reported that BDSP was changed to bethamethasone base molecule inside the intact microparticles. The best drug to polymers ratio in microparticles was F 1 containing 50 mg drug, 50 mg HPMC (as non-ionic and hydrophilic polymer) and 50 mg carbomer 934p (an anionic mucoadhesive polymer). The production yield of F1 microparticles was calculated as 78.60% with loading efficiency of about 65.14% and the mean particle size was also measured as 281.84 μm. It was proposed that during the microparticle preparation procedure, water soluble salt of the drug may be converted to the base which could be more effective in the buccal mucosa due to its higher partition coefficient and lipophilicity. The highest and lowest releases resulted from the discs prepared from F 1 and F 4 , respectively, compared with the commercial tablet and untreated drug powder (p < 0.05). The data revealed that the discs exhibited good percentage of mucoadhesion (F 1 , 326 g/cm 2 ). It may be concluded that drug loaded buccal-mucoadhesive microparticles are a suitable delivery system for BDSP, and may be used in the effective management of lichen planus.

Context: Betamethasone (BMZ) is an effective drug which is commonly used as an eye drop for the management of ophthalmic inflammations. Due to low ocular bioavailability, it is necessary to prepare and optimize an ocular drug delivery system for BMZ., Objective: In this study we tried to use vitamin E diffusion barrier for sustaining BMZ release., Materials and Methods: Three commercial contact lenses were soaked in vitamin E solutions and swelling percentage, diameter, transmittance, binding capacity and release amount and time were evaluated in comparison with non-vitamin E-loaded pure lenses., Results: The results showed that vitamin E significantly decreased water content of contact lenses whereas, increased the lens diameter in both dry and wet states. It effectively blocked UV radiation which is harmful for the eye surface while had no significant effect on visible transmittance. BMZ loading capacity enhanced and release rate remarkably decreased after using vitamin E as a hydrophobic diffusion barrier., Discussion and Conclusions: This study revealed that vitamin E can be applied as a hydrophobic diffusion barrier for controlling and sustaining BMZ release from silicone-based soft contact lenses into the lachrymal fluid. It can also protect eye tissues as an antioxidant by blocking the UV radiation.

In this study, mesoporous silica particles with a hexagonal structure (SBA-15) were synthesized and modified with (3-aminopropyl) triethoxysilane, and used as a carrier for anti-inflammatory drug, betamethasone sodium phosphate. Drug-loaded silica particles were grafted on the cotton fabric surface using chitosan and polysiloxane reactive softener as a soft and safe fixing agent to develop an antibacterial cotton fabric with drug delivery properties. Cytometry assays revealed that synthesized silica have no cytotoxicity against human peripheral blood mononuclear cells. Accordingly, the produced drug-loaded nanostructures can be applied via different routes, such as wound dressing. Drug delivery profile of the treated fabrics were investigated and compared. The drug release rate followed the conventional Higuchi model. The treated cotton fabrics were tested and evaluated using scanning electron microscope images, bending length, air permeability, washing durability and anti-bacterial properties. It was found that the chitosan-/softener-treated fabrics compounded with drug-loaded silica particles have a good drug delivery performance and exhibited a powerful antibacterial activity against both Escherichia coli and Staphylococcus aureus even after five washing cycles. The produced antibacterial cotton fabric with drug delivery properties could be proposed as a suitable material for many medical and hygienic applications.

Background: Calcipotriene 0.005% (Cal)/betamethasone dipropionate 0.064% (BD) aerosol foam was developed as a new treatment option for patients with psoriasis. This pooled analysis evaluated the efficacy of this formulation for 4 weeks of treatment.
, Methods: Patients aged &ge;18 years with mild-severe psoriasis were enrolled into three Phase II/III studies (nCT01536886, nCT01536938, nCT01866163); each study evaluated Cal/BD aerosol foam versus different comparators. Endpoints included: proportion of patients clear/almost clear with &ge;2-step improvement in physician's global assessment of disease severity ('treatment success'); modified (excluding head) psoriasis area and severity index (mPASI); proportion of patients with &ge;75% reduction in mPASI (PASI75); change in itch (according to visual analog scale [VAS]).
, Results: 1104 patients were included in the pooled analysis: Cal/BD aerosol foam (n=564), Cal/BD ointment (n=135), BD aerosol foam (n=101), Cal aerosol foam (n=101), aerosol foam vehicle (n=152), ointment vehicle (n=51). At week 4, 51% of Cal/BD aerosol foam patients achieved treatment success, a higher proportion than in all other groups (Cal/BD ointment, 43%; BD aerosol foam, 31%; Cal aerosol foam, 15%; aerosol foam vehicle, 5%; ointment vehicle, 8%). Greater percentage mean decrease in mPASI with Cal/BD aerosol foam was noted versus other treatments at week 4 (72% vs 63%, 53%, 43%, 32%, and 33%, respectively); week 4 PASI75 rate was also greater (51% vs 41%, 34%, 18%, 7%, and 10%, respectively). Cal/BD aerosol foam was efficacious irrespective of baseline disease severity and on all body areas assessed (arms, legs, trunk). Cal/BD aerosol foam alleviated itch as early as week 1 (change in itch VAS: -30 mm), maintained to week 4 (change in itch VAS: -41 mm).
, Conclusions: Cal/BD aerosol foam was significantly more effective than Cal/BD ointment and the individual active ingredients for treating psoriasis vulgaris, resulting in greater and faster reduction in disease severity and rapid, effective relief of itch.

J Drugs Dermatol. 2016;15(8):951-957.

Introduction: Psoriasis has a major impact on patient quality of life, similar to that seen in other chronic diseases, eg, diabetes. Health-related quality of life (HRQoL) measures are commonly included in clinical trial designs, capturing the disease burden and therapeutic success of a treatment. In the randomized, double-blind, phase III PSO-FAST ( Pso riasis vulgaris, a F our-week, vehicle-controlled, efficacy A nd S afety T rial) study (nCT01866163), fixed combination calcipotriene (Cal) 0.005% plus betamethasone dipropionate (BD) 0.064% aerosol foam was compared with vehicle. By treatment end, 53% of patients using Cal/BD foam achieved treatment success.
, Objective: To compare the impact on HRQoL of Cal/BD foam vs vehicle in patients with mild-to-severe psoriasis.
, Method: HRQoL was assessed by dermatology life-quality index (DLQI; baseline, weeks 1, 2, 4) and EQ-5D-5L (EQ-5D; baseline, week 4) questionnaires. A DLQI score of 0 (range, 0-30) indicates no effect on the patient's life; an EQ-5D utility score of 1 (range, 0-1) and an EQ-5D visual analog scale (VAS) score of 100 (range, 1-100) indicate perfect health.
, Results: 426 patients were randomized (Cal/BD foam, n=323; vehicle, n=103). Baseline mean DLQI scores were 9.9 (Cal/BD foam) and 10.3 (vehicle). The impact of psoriasis on HRQoL (EQ-5D utility score) at baseline was primarily driven by pain/discomfort (Cal/BD foam: 69.9%; vehicle: 65.0%) and anxiety/depression (Cal/BD foam: 45.3%; vehicle 44.7%). There was a greater improvement from baseline in DLQI score for Cal/BD foam vs vehicle at week 4 (-7.0 vs -4.4; P&lt;.001); increased improvement was also seen in EQ-5D scores. At week 4, 48.1% of patients using Cal/BD foam reported no effect of psoriasis on their lives (DLQI = 0/1), and of patients using Cal/BD foam with baseline DLQI scores ≥5, 81.2% achieved a &ge;5-point improvement.
, Conclusion: Cal/BD aerosol foam improved HRQoL after 4 weeks, with most patients experiencing a clinically meaningful improvement and almost 50% reporting no impairment., , J Drugs Dermatol. 2016;15(8):981-987.

Background: A novel formulation of 0.05% betamethasone dipropionate in an emollient spray vehicle (DFD-01) was developed to deliver steroid to the skin layers most affected by psoriasis., Objective: To compare the efficacy and safety of DFD-01 to its vehicle for the treatment of moderate plaque psoriasis over 4 weeks., Methods: Two Phase 3 trials enrolled adults with moderate psoriasis (Investigator Global Assessment [IGA]=3; 10-20% body surface area [BSA]) and randomized them 2:1 to DFD-01 or Vehicle. Products were applied twice daily to affected areas for 28 days. Treatment success was defined as an IGA=0 or 1 and ≥ 2-grade improvement from baseline. Primary endpoint was the proportion of subjects achieving treatment success at day 15., Results: Moderate psoriasis subjects were enrolled in Study 1 (174 DFD-01; 87 Vehicle) and Study 2 (182 DFD-01; 95 Vehicle). Mean BSA was 13-14%. Treatment success was achieved in significantly more subjects using DFD-01 than Vehicle at day 15 in both Study 1 (P<0.001) and Study 2 (P=0.002), and at day 29 (both studies P<0.001). Treatment success with DFD-01 was significant at day 8 in Study 1 (P=0.003) but not in Study 2 (P=0.156). Erythema, scaling, and plaque elevation scores of target lesions were significantly reduced as early as day 4 with DFD-01. Adverse events were similar between groups, with no increase between 2 and 4 weeks., Conclusion: These studies demonstrate DFD-01's excellent efficacy and safety for the treatment of extensive psoriasis (10-20% BSA). DFD-01 achieved treatment success in significantly more subjects than Vehicle after 2 and 4 weeks of treatment, and showed early onset of action with improved signs of erythema, scaling and elevation of target lesions after 4 days of treatment. This medium potency formulation provides a safe and effective choice for topical steroid treatment of psoriasis.

The association of vegetable products to nanostructured systems has attracted the attention of researchers due to several advantages, such as drug photoprotection, as well as the improvement of the pharmacological and therapeutic activities because of synergistic action, which can provide their topical application. In this work, lipid-core nanocapsules containing borage oil as oil core and betamethasone dipropionate were developed, and nanocapsules without the drug were prepared for comparison. The suspensions were characterized in relation to mean particle size, zeta potential, pH, drug content, and encapsulation efficiency. A photodegradation study was carried out and the in vitro release profile as well as the irritation potential of the drug after nanoencapsulation were also evaluated. In addition, the antiproliferative activity of the free borage oil as well as loaded in nanocapsules was studied. Lipid-core nanocapsules showed nanometric mean size (185-210 nm); polydispersity index below 0.10; negative zeta potential and pH slightly acid (6.0-6.2). Moreover, the drug content was close to theoretical concentration (0.50 +/- 0.03 mg/ml of betamethasone), and the encapsulation efficiency was approximately 100%. The study of the antiproliferative activity of borage oil showed ability to reduce cell growth of Allium cepa. The nanoencapsulation of betamethasone dipropionate provided greater protection against UVC light and decreased the irritation potential of the drug. The release profile of betamethasone dipropionate from nanocapsules followed monoexponential model.

Mesoporous silica nanoparticles with a hexagonal structure (SBA-15) were synthesized and modified with (3-aminopropyl) triethoxysilane (APTES), and their performance as a carrier for drug delivery system was studied. Chemical structure and morphology of the synthesized and modified SBA-15 were characterized by SEM, BET, TEM, FT-IR and CHN technique. Betamethasone Sodium Phosphate (BSP) as a water soluble drug was loaded on the mesoporous silica particle for the first time. The response surface method was employed to obtain the optimum conditions for the drug/silica nanoparticle preparation, by using Design-Expert software. The effect of time, pH of preparative media, and drug/silica ratio on the drug loading efficiency was investigated by the software. The maximum loading (33.69%) was achieved under optimized condition (pH: 1.8, time: 3.54 (h) and drug/silica ratio: 1.7). The in vitro release behavior of drug loaded particles under various pH values was evaluated. Finally, the release kinetic of the drug was investigated using the Higuchi and Korsmeyer-Peppas models. Cell culture and cytotoxicity assays revealed the synthesized product doesn't have any cytotoxicity against human bladder cell line 5637. Accordingly, the produced drug-loaded nanostructures can be applied via different routes, such as implantation and topical or oral administration., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Case reports of catastrophic neurological sequelae during ESIs have questioned the safety of this procedure. A proposed mechanism is particulate steroid embolization resulting in neuralischemia. Previous reports have described steroid clumping in common epidural injection mixtures. We demonstrate that physiologic medium can also modify aggregation., Objective: To inspect and compare aggregative properties of steroid preparations with and without human serum., Setting: Academic tertiary care center., Hypothesis: Particulate steroids display different aggregation characteristics in serum compared to non-physiologic solutions., Design: Solutions were inspected under light microscopy: betamethasone sodium phosphate/betamethasone acetate, methylprednisolone, and dexamethasone were each mixed in lidocaine 1%, bupivacaine 0.5%, or sterile water in a 1:1 ratio. All preparations were inspected under light microscopy with 100x and 400x magnifications by a pathologist blinded to our expectations and hypothesis. Five random viewing fields were selected within each slide and the number of aggregates per field and the number of particles per aggregate was evaluated., Results: The addition of serum had a significant effect on steroid particle aggregation and number of particles per aggregate., Limitations: This study was limited by sample size as only 2 sets of human serum samples were tested with each preparation against one non-serum control. Additionally, as steroid preparations were evaluated under light microscopy, the ex vivo setting must be considered in the interpretation of results. Finally, mixing preparations with human serum as opposed to whole blood was necessary to allow for improved visibility on light microscopy despite the fact that whole blood may be necessary to more closely emulate in vivo coagulation setting., Conclusions: Overall, the presence of serum resulted in fewer large steroid particle aggregates when compared to non-serum control samples. Amongst particulate steroids, betamethasone with bupivacaine 0.5% demonstrated the fewest and smallest particle aggregates, suggesting that preparation may reduce the risk of embolic infarction. Methylprednisolone formed significantly larger particles in bupivicaine 0.5% with serum compared to non-serum controls.

Topical glucocorticosteroids were incorporated into nanocarrier-based formulations, to overcome side effects of conventional formulations and to achieve maximum skin deposition. Nanoparticulate carriers have the potential to prolong the anti-inflammatory effect and provide higher local concentration of drugs, offering a better solution for treating dermatological conditions and improving patient compliance. Nanoparticles were formulated with poly-ϵ-caprolactone as the polymeric core along with stearic acid as the fatty acid, for incorporation of betamethasone-21-acetate. Oleic acid was applied as the coating fatty acid. Improvement of the drug efficacy, and reduction in drug degradation with time in the encapsulated form was examined, while administering it locally through controlled release. Nanoparticles were spherical with mean size of 300 nm and negatively charged surface. Encapsulation efficiency was 90%. Physicochemical stability in aqueous media of the empty and loaded nanoparticles was evaluated for six months. Drug degradation was reduced compared to free drug, after encapsulation into nanoparticles, avoiding the potency decline and promoting a controlled drug release over one month. Fourier transform infrared spectroscopy and thermal analysis confirmed drug entrapment, while cytotoxicity studies performed in vitro on human keratinocytes, Saccharomyces cerevisiae models and Artemia salina, showed a dose-response relationship for nanoparticles and free drug. In all models, drug loaded nanoparticles had a greater inhibitory effect. Nanoparticles increased drug permeation into lipid membranes in vitro. Preliminary safety and permeation studies conducted on rats, showed betamethasone-21-acetate in serum after 48 h application of a gel containing nanoparticles. No skin reactions were observed. In conclusion, the developed nanoparticles may be applied as topical treatment, after encapsulation of betamethasone-21-acetate, as nanoparticles promote prolonged drug release, increase drug stability in aqueous media, reducing drug degradation, and increase drug permeability through lipid membranes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The filling process of liquid suspensions is a difficult operation,mainly due to drug settling. Small variations during the process may lead to serious deviations in the API content uniformity of the finished product, particularly if the drug settles fast. Real-time non-invasive monitoring of liquid suspensions is a useful approach to ensure an acceptable API content in the finished product. The aim of this study was to develop a method based on non-invasive turbidity measurements for in-line determinations of betamethasone content uniformity during the filling process of injections. Owing to the constructive features of the developed system, the determinations were performed in a non-destructive and non-invasive way, thus allowing the analysis of the whole batch and minimizing the risk of contaminating the product. The results obtained by the method proposed in this study demonstrated that non-invasive turbidimetry is a powerful tool for continuous monitoring of the filling process of betamethasone injections, within the Quality by Design framework (FDA, 2009)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The lipophilicity (R(MW)) of betamethasone and its four related compounds: betamethasone-17,21-dipropionate, betamethasone-17-valerate, betamethasone-21-valerate and also betamethasone disodium phosphate was determined by reversed phase HPTLC and various mobile phase systems (methanol-water, dioxane-water and acetonitrile-water). The chromatographic lipophilicity parameters obtained for all examined compounds using abovementioned mobile phases onto three chromatographic plates (RP-2F254, RP-8F254, RP-18WF254) were compared with the theoretical partition coefficients which have been calculated by different computing programs: AlogPs, AClogP, AlogP, MlogP, KOWWIN, xlogP2, xlogP3, logP(ChemDraw) as well as with logP measured by shake-flask method. The results of this work demonstrate that regardless of applied method the greatest similarity in lipophilic properties show betamethasone-17-valerate, betamethasone-21-valerate and also betamethasone 17,21-dipropionate. The influence of solvent system as mobile phase on R(MW) values of examined compounds was observed. Among different mobile phases (organic modifier-water) proposed in this study, which allowed obtaining the reliable chromatographic lipophilicity parameters for all studied compounds is methanol-water mixture. The performance investigations showed that RP-HPTLC method has proved to be a rapid and cost effective analytical tool for describing the lipophilic properties of betamethasone and its related compounds.

Aim: The primary aim of present work was to develop effective combination drug therapy for topical treatment of psoriasis., Methods: Betamethasone dipropionate and calcipotriol loaded solid lipid nanoparticles (CT-BD-SLNs) were prepared by hot melt high shear homogenization technique, which were then incorporated in Carbopol gel matrix. The anti-psoriatic potential was tested by sequential in vitro (skin permeation and dermal distribution, anti-proliferative effect in HaCaT cells) and in vivo (Draize patch irritation, transepidermal water loss (TEWL) and anti-psoriatic mouse tail studies) experiments., Results: A negligible amount in receptor compartment, yet confined distribution of drugs to epidermal and dermal region of skin was observed in case of SLNs, which is essential for safe and effective anti-psoriatic therapy. Draize patch test and TEWL demonstrated negligible skin irritation and better skin tolerability of SLNs. The in vitro HaCaT cell line study demonstrated that SLNs delayed the abrupt growth of keratinocytes, while in vivo mouse tail model showed that SLNs gel significantly decreased the epidermal thickness and increased melanocyte count in comparison to commercial Daivobet® ointment., Conclusions: The developed SLNs gel is expected to be potential strategies for treatment of psoriasis and other topical diseases.

Silica-based sol-gel coatings have gained attention in bone therapies and orthopedic applications, due to the biocompatibility and bioactivity, including a high potential for the controlled release both in vitro and in vivo. Bioactive materials are created to facilitate the biocompatibility of orthopedic implants. One of the promising alternatives is biomaterials with immobilized drugs. In this study we demonstrated for the first time novel sol-gel-derived silica coatings with active amino groups (SiO2(NH2)) functionalized with a steroid drug-betamethasone, applied to a substrate 316 L using dip coating technique. The presence of betamethasone in functionalized coatings was directly confirmed by Raman spectroscopy and energy-dispersive X-ray spectroscopic analysis. The wettability was evaluated by the sessile drop method, while the surface free energy was estimated based on the contact angles measured. Our results showed a shift in surface properties from hydrophobic to hydrophilic after application of the coatings. We have investigated the morphology, proliferation factor, and the population doubling time of adipose-derived stem cells for biological purposes. Moreover, the analysis of the distribution and localization of cellular microvesicles was performed to evaluate the influence of functionalized surfaces on cellular cytophysiological activity. Increased proliferation and activation of cells, determined by the observations of microvesicles shedding processes, provided evidence of the availability of the drug. Therefore, we conclude that the sol-gel synthesis proposed here allows to improve the metal substrates and can be successfully used for immobilization of betamethasone. This in turn enables the direct delivery of the drug with implanted material into the wound site, and to stimulate the activity of cells to enhance tissue regeneration., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Novel magnetic molecularly imprinted nanoparticles (MMIPs) using N,N-p-phenylene bismethacryl amide as a cross linker and super paramagnetic core-shell nanoparticle as a supporter for use in controlled release were prepared by precipitation polymerization. Novel cross-linking agents were synthesized by the reaction of methacryloyl chloride with p-phenylenediamine. Then, the Fe3O4 nanoparticles were encapsulated with a SiO2 shell and functionalized with -CH=CH2 and MMIPs were further prepared by using methacrylic acid as a functional monomer, N,N-p-phenylene bismethacryl amide as a cross-linking agent and betamethasone as template. Magnetic non-MIPs were also prepared with the same synthesis procedure as with MMIPs only without the presence of the template. The obtained MMIPs were characterized by using transmission electron microscopy, Fourier transform infrared spectrum, X-ray diffraction, energy-dispersive X-ray spectroscopy, and the vibrating sample magnetometer. The performance of the MMIPs for the controlled release of betamethasone was assessed and results indicated that the magnetic MIPs also had potential applications in drug controlled release.

Background: Antenatal inflammation and maternal corticosteroids induce fetal lung maturation but interfere with late lung development. Canonical Wingless-Int (Wnt) signaling directs lung development and repair. We showed that intra-amniotic (IA) lipopolysaccharide (LPS) exposure disrupted developmental signaling pathways in the preterm lamb lungs. Therefore, we hypothesized that pulmonary Wnt signaling was altered by exposure to IA LPS and/or antenatal corticosteroids., Methods: Ovine fetuses were exposed to IA LPS, maternal intramuscular betamethasone, a control saline injection, or a combination thereof at 107 and/or 114 d gestational age (term = 150 d gestational age) before delivery at 121 d gestational age., Results: IA LPS exposure decreased the lung expression of lymphoid enhancer-binding factor 1 (LEF1), a major Wnt pathway effector. WNT1, WNT4, and downstream messenger β-catenin decreased after LPS exposure. WNT7b mRNA increased fourfold 14 d post-LPS exposure. Betamethasone treatment 7 d before LPS exposure prevented the reduction in LEF1 expression, whereas betamethasone administration after LPS normalized the LPS-induced increase in Wnt7b mRNA., Conclusion: IA LPS exposure decreased canonical Wnt signaling in the developing lung. Antenatal corticosteroids before or after IA inflammation had different effects on pulmonary Wnt signaling. This study provides new insights into possible mechanisms by which prenatal inflammation affects lung development and how corticosteroid can be beneficial in this setting.

Cerebral malaria (CM) is a severe complication of and a leading cause of death due to Plasmodium falciparum infection. CM is likely the result of interrelated events, including mechanical obstruction due to parasite sequestration in the microvasculature, and upregulation of Th1 immune responses. In parallel, blood-brain-barrier (BBB) breakdown and damage or death of microglia, astrocytes, and neurons occurs. We found that a novel formulation of a liposome-encapsulated glucocorticosteroid, β-methasone hemisuccinate (nSSL-BMS), prevents experimental cerebral malaria (ECM) in a murine model and creates a survival time-window, enabling administration of an antiplasmodial drug before severe anemia develops. nSSL-BMS treatment leads to lower levels of cerebral inflammation, expressed by altered levels of corresponding cytokines and chemokines. The results indicate the role of integrated immune responses in ECM induction and show that the new steroidal nanodrug nSSL-BMS reverses the balance between the Th1 and Th2 responses in malaria-infected mice so that the proinflammatory processes leading to ECM are prevented. Overall, because of the immunopathological nature of CM, combined immunomodulator/antiplasmodial treatment should be considered for prevention/treatment of human CM and long-term cognitive damage.