Stability Of Dexamethasone Research Articles

Stability of Dexamethasone during Hot-Melt Extrusion of Filaments based on Eudragit® RS, Ethyl Cellulose and Polyethylene Oxide

Hot-melt extrusion (HME) potentially coupled with 3D printing is a promising technique for the manufacturing of dosage forms such as drug-eluting implants which might even be individually adapted to patient-specific anatomy. However, these manufacturing methods involve the risk of thermal degradation of incorporated drugs during processing. In this work, the stability of the anti-inflammatory drug dexamethasone (DEX) was studied during HME using the polymers Eudragit® RS, ethyl cellulose and polyethylene oxide. The extrusion process was performed at different temperatures. Furthermore, the influence of accelerated screw speed, the addition of the plasticizers triethyl citrate and polyethylene glycol 6000 or the addition of the antioxidants butylated hydroxytoluene and tocopherol in two concentrations were studied. The DEX recovery was analyzed by a high performance liquid chromatography method suitable for the detection of thermal degradation products. The strongest impact on the drug stability was found for the processing temperature, which was found to reduce the DEX recovery to <20% for certain processing conditions. In addition, differences between tested polymers were observed, whereas the use of additives did not result in remarkable changes in drug stability. In conclusion, suitable extrusion parameters were identified for the processing of DEX with high drug recovery rates for the tested polymers. Moreover, the importance of a suitable analysis method for drug stability during HME that is influenced by several parameters was highlighted.

Dexamethasone does not affect endolymphatic hydrops (EH) in patients with Meniere's disease within 24 h, and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min

BackgroundIntratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops (EH) using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min. The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI. Materials and methodsIn an in vitro study, the potential impact of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography (HPLC) after mixing with Gd-DTPA. Ten patients with definite Meniere's disease (MD) were recruited to study the potential interference of dexamethasone on MRI visualization of EH, and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation (hT2FLAIR-MZFI) sequence. ResultsThe retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA. EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone. Excellent inner ear images were obtained from all patients, and EHs with various grades were displayed. There were significant correlations between diagnosis and cochlear EH (p < 0.01, Spearman's Rho), between diagnosis and vestibular EH (p < 0.01, Spearman's Rho), and between cochlear and vestibular EH (p < 0.01, Spearman's Rho). The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH. Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD. ConclusionsIntratympanic administration of Gd-DTPA plus dexamethasone yielded high-quality MRI images of EH in patients with MD using a novel 7-min protocol and simplified the clinical application. Intratympanic administration of Gd-DTPA plus dexamethasone might be used to test its therapeutic effect in future work. Level of evidence3.

Dexamethasone Incorporating Liposomes: Effect of Lipid Composition on Drug Trapping Efficiency and Vesicle Stability

Effect of lipid composition on encapsulation and stability of dexamethasone (DXM) incorporating multilamellar vesicles (MLV) is studied. MLVs composed of phosphatidylcholine (PC) or distearoyl-glycero-PC (DSPC), with or without cholesterol (Chol), are prepared and the release of DXM during vesicle incubation in buffer or plasma proteins is evaluated. Incorporation of DXM is slightly higher in DSPC liposomes compared with PC, whereas the drug is displaced from liposomes, as the Chol content of liposome membranes increases. Plain lipid and Chol-containing liposomes lose similar fractions of vesicle-incorporated DXM during incubation in buffer or serum, whereas DXM release kinetics are similar (for each liposome type studied), implying that drug release is due mainly to dilution of liposome dispersions that leads to repartitioning of DXM.

A chromatography method for the screening and confirmatory detection of dexamethasone

Corticosteroids, such as dexamethasone, have been illegally used as growth promoting agents to obtain an economical benefit from increased muscle development. These substances remain in meat and other animal products and may have negative toxic consequences for consumers. A screening and confirmatory method for dexamethasone detection in feed and drinking water in livestock has been developed and validated. This method is based on immunoaffinity chromatography followed by reverse-phase high-performance liquid chromatrography (IAC–HPLC) with diode array detection (DAD) at 242 nm. Flumethasone was used as internal standard. The method has been validated according to the European Union regulation 2002/657/EC for banned substances and, thus, the specificity, decision limit, detection capability, recovery and repeatability have been determined. The decision limits (CCα) were 26 ng/mL for water and 190 ng/g for feed while detection capabilities (CCβ) were 30 ng/mL for water and 217 ng/g for feed. The method showed good accuracy and precision. The stability of dexamethasone under frozen storage has been studied over a 3.5-month period. No losses were observed, thus confirming that water samples taken by inspectors can be stored frozen for a few weeks until analysis. This method has proved to be relatively simple and useful for rapid screening and confirmation of the presence of dexamethasone in water and feed used for meat-producing animals.

Stability of Dexamethasone in Extemporaneously Prepared Oral Suspensions

ABSTRACT Objective: To evaluate the stability of 0.5 and 1.0 mg/mL dexamethasone suspensions in a vehicle consisting of equal parts of Ora-Sweet and Ora-Plus after storage at 4°C and 25°C for up to 91 days. Methods: Suspensions of dexamethasone sodium phosphate 4 mg/mL injection solution in a 1:1 mixture of Ora-Sweet and Ora-Plus were prepared in 40-mL amber plastic bottles; final concentrations of dexamethasone were 0.5 and 1.0 mg/mL. Three bottles of each suspension were stored at 4°C (refrigerated), and 3 were stored at 25°C (room temperature). Physical characteristics, including pH, colour, odour, viscosity, precipitation, and ease of resuspension, were observed weekly for 91 days. Aliquots were removed from each bottle weekly for 91 days and stored at –84°C until analysis by a validated high-pressure liquid chromatography method. A suspension was considered stable if it maintained 90% of its initial concentration. Results: No change in pH was observed in suspensions of either concentration after storage at 4°C or 25°C for 91 days. Changes in colour and odour were slight. Viscosity was constant. Precipitates were easily resuspended, and there was no caking or clumping of material. Suspensions of both concentrations of dexamethasone maintained at least 90% of initial concentration at both temperatures throughout the 91-day period. Conclusions: Dexamethasone suspensions of both 0.5 and 1.0 mg/mL in a 1:1 mixture of Ora-Sweet and Ora-Plus were physically and chemically stable for a period of up to 91 days, with or without refrigeration. The expiry date for these products can therefore be set at 91 days. RESUME Objectif : Evaluer la stabilite de suspensions de dexamethasone a des concentrations de 0,5 et 1,0 mg/mL dans un excipient liquide compose a parts egales d’Ora Sweet et d’Ora Plus, apres entreposage a 4 °C et 25 °C pendant une periode allant jusqu’a 91 jours. Methodes : Les suspensions de phosphate sodique de dexamethasone a raison de 4 mg/mL de solution pour injection dans un melange 1:1 d’Ora-Sweet et d’Ora-Plus ont ete preparees dans des flacons de plastique ambre de 40 mL; les concentrations finales de dexamethasone etaient de 0,5 et 1,0 mg/mL. Trois flacons de chaque suspension ont ete entreposes a 4 °C (au refrigerateur) et trois autres a 25°C (a la temperature ambiante). Les caracteristiques physiques, don le pH, la couleur, l’odeur, la viscosite, la precipitation et la facilite de remise en suspension ont ete examinees a chaque semaine pendant les 91 jours. Les aliquotes ont ete retirees de chaque flacon a toutes les semaines, pendant les 91 jours, et refrigerees a –84 °C avant d’etre analysees par une methode validee de chromatographie liquide a haute pression. La suspension etait consideree stable lorsqu’elle conservait 90 % de sa concentration initiale. Resultats : Aucun changement du pH n’a ete observe dans l’une ou l’autre des suspensions aux deux concentrations, apres leur entreposage a 4 °C ou 25 °C pendant 91 jours. Une legere alteration de la couleur et de l’odeur est cependant survenue. La viscosite etait stable et les precipites ont ete facilement remis en suspension, sans agglomeration ni agglutination de la matiere. Les suspensions des deux concentrations de dexamethasone ont conserve au moins 90 % de leur concentration initiale aux deux temperatures pendant la periode d’etude de 91 jours. Conclusions : Les suspensions de dexamethasone aux concentrations de 0,5 et 1 mg/mL dans un melange 1:1 d’Ora Sweet et d’Ora Plus ont montre une stabilite physique et chimique pendant une periode allant jusqu’a 91 jours, avec ou sans refrigeration. La date de peremption de ces produits peut par consequent etre etablie a 91 jours.

High affinity binding and regulatory actions of dexamethasone-type I receptor complexes in mouse brain.

It is often implied that the various molecular, physiological, and behavioral responses to the glucocorticoid dexamethasone (DEX) are mediated in brain exclusively via the interactions of this synthetic steroid with the classical glucocorticoid (type II) receptor. The results reported in this study, however, suggest this generalization may, at least for the female mouse, be too restrictive. In the first experiment we compared the efficacy of the mineralocorticoid aldosterone (ALDO) with that of DEX to measure the classical mineralocorticoid (type I) receptor in brain cytosol. Since both of these steroids also bind to type II receptors, our assays included the type II receptor-selective ligand, RU26988. Whereas the specific binding of ALDO to type I receptors was largely unaffected by a 10-fold increase in the concentration of RU26988 (50- vs. 500-fold excess), there was a dramatic reduction in the specific binding of DEX. In a follow-up experiment, Scatchard analyses were used to confirm the differential affinity of RU26988 for DEX- vs. ALDO-type I receptor-binding sites and to reveal that the affinity of type I receptors for DEX (Kd approximately 0.83 nM) was nearly as high as it was for ALDO (Kd approximately 0.46 nM). A series of competition studies indicated that the competitive affinity (Kdc) of DEX for the ALDO-binding site was equivalent to the Kd computed in the saturation analyses, thus suggesting that the high affinity binding sites for DEX and ALDO on type I receptors may be equivalent or at least overlapping. The binding of DEX to these high affinity sites may prove to be important, since the systemic administration of this steroid was found to down-regulate both type I and type II receptors in a number of brain regions. Because coadministration of the type I receptor antagonist RU26752 was shown to block these actions on type I, but not type II receptors, the formation of the DEX-type I receptor complex appears to be required for DEX-induced type I receptor down-regulation. An analysis of the in vitro efficacy of ALDO- vs. DEX-type I receptor transformation suggests that whereas there is a significant increase in the binding of both complexes to DNA-cellulose after treatment with thiocyanate, there is also a dramatic decrease in the stability of DEX- but not ALDO-type I receptor binding. We contend that it is this decrease in binding stability that mediates the DEX-induced down-regulation of type I receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Stability Test of Dexamethasone in Vanishing Creams of Various pH by High Speed Liquid Chromatography

The stability of dexamethasone (DMS) in vanishing creams of various pH was studied. Vanishing creams containing 1% MDS were exposed to air at 40° and stability of DMS was measured by using high speed liquid chromatography (HSLC). The conditions of HSLC were as follows: model: JASCO FLC-350; detector: UVIDEC-1; wavelength: 239nm; column: HP-01 (copolymer of styrene-divinylbenzene) 4.5×250 mm; mobile phase: MeOH; flow rate: 1 ml/min; pressure: 40kg/cm2 (at room temperature). The extracted DMS was directly injected into the HSLC column and its stability was determined from the peak height of DMS on the chromatogram. It was found that DMS in vanishing creams was unstable under the basic condition and the decomposition product of DMS in vanishing creams was 3, 17-ketosteroid.