Características físicas y propiedades de disolución de dispersiones sólidas de oxazepam con carbómero 934P

The formulation of solid dispersions is an effective method of increasing the dissolution rate of poorly soluble drugs.The purpose of this study was to prepare and to characterize solid dispersions of oxazepam with carbomer 934P toimprove their dissolution properties. Solid dispersions were prepared by dissolution method and the dissolution rates ofsolid dispersions were compared with those ones of physical mixtures and pure drug. The evaluation of solid dispersionscharacteristics was performed using infrared espectroscopy (IR), X-ray diffractometry (X-R), differential scanning calorimetry(DSC) and dissolution assay. IR, X-R and DSC data showed no drug-polymer interaction. The results obtainedfrom dissolution studies showed that the dissolution rate of oxazepam was considerably better when it was formulatedin solid dispersions with carbomer 934P compared with those of physical mixtures and pure oxazepam.La formulación de dispersiones sólidas es un método efi caz de aumento de la velocidad de disolución de fármacosmuy poco solubles. El objetivo de este estudio fue la preparación y caracterización de dispersiones sólidas de oxazepamcon carbómero 934P para mejorar sus propiedades de disolución. Las dispersiones sólidas se prepararonmediante el método de disolución y se compararon las velocidades de disolución de dispersiones sólidas con las delas mezclas físicas y el fármaco puro. La evaluación de las características de las dispersiones sólidas se realizó medianteespectroscopia de infrarrojos (IR), difractometría de rayos X (R-X), calorimetría diferencial de barrido (DSC)y ensayo de disolución. Los datos de IR, R-X y DSC no mostraron interacción fármaco-polímero. Los resultadosobtenidos a partir de los estudios de disolución mostraron que la velocidad de disolución del oxazepam mejorabaconsiderablemente cuando se formulaba en dispersiones sólidas con carbómero 934P, en comparación con las demezclas físicas y el oxazepam puro

The effectiveness of ω-3 polyunsaturated fatty acid interventions during pregnancy on obesity measures in the offspring: an up-to-date systematic review and meta-analysis.

BACKGROUND: The potential role of ω-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on subsequent risk of obesity outcomes in the offspring is not clear and there is a need to synthesise this evidence. OBJECTIVE: A systematic review and meta-analysis of randomised controlled trials (RCTs), including the most recent studies, was conducted to assess the effectiveness of ω-3 LCPUFA interventions during pregnancy on obesity measures, e.g. BMI, body weight, fat mass in offspring. METHODS: Included RCTs had a minimum of 1-month follow-up post-partum. The search included CENTRAL, MEDLINE, SCOPUS, WHO's International Clinical Trials Reg., E-theses and Web of Science databases. Study quality was evaluated using the Cochrane Collaboration's risk of bias tool. RESULTS: Eleven RCTs, from ten unique trials, (3644 children) examined the effectiveness of ω-3 LCPUFA maternal supplementation during pregnancy on the development of obesity outcomes in offspring. There were heterogeneities between the trials in terms of their sample, type and duration of intervention and follow-up. Pooled estimates did not show an association between prenatal intake of fatty acids and obesity measures in offspring. CONCLUSION: These results indicate that maternal supplementation with ω-3 LCPUFA during pregnancy does not have a beneficial effect on obesity risk. Due to the high heterogeneity between studies along with small sample sizes and high rates of attrition, the effects of ω-3 LCPUFA supplementation during pregnancy for prevention of childhood obesity in the long-term remains unclear. Large high-quality RCTs are needed that are designed specifically to examine the effect of prenatal intake of fatty acids for prevention of childhood obesity. There is also a need to determine specific sub-groups in the population that might get a greater benefit and whether different ω-3 LCPUFA, i.e. eicosapentaenoic (EPA) vs. docosahexanoic (DHA) acids might potentially have different effects

Coupling of receptor conformation and ligand orientation determine graded activity

Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-allostery' mutations that mimic the effects of ligand in driving protein conformation allowed crystallization of the partial agonist ligand WAY-169916 with both the canonical active and inactive conformations of the estrogen receptor. The intermediate transcriptional activity induced by WAY-169916 is associated with the ligand binding differently to the active and inactive conformations of the receptor. Analyses of a series of chemical derivatives demonstrated that altering the ensemble of ligand binding orientations changes signaling output. The coupling of different ligand binding orientations to distinct active and inactive protein conformations defines a new mechanism for titrating allosteric signaling activity.John B. Bruning, Alexander A. Parent, German Gil, Min Zhao, Jason Nowak, Margaret C. Pace, Carolyn L. Smith, Pavel V. Afonine, Paul D. Adams, John A. Katzenellenbogen and Kendall W. Nettle