Coprocessing via spray drying as a formulation platform to improve the compactability of various drugs

‘Coprocessing’ door middel van sproeidrogen werd ontwikkeld als een alternatieve productietechniek om de compacteerbaarheid van hoog gedoseerde en slecht comprimeerbare geneesmiddelen te verhogen. In tegenstelling tot (natte) granulatietechnieken is een dergelijk productieproces volledig continu. Er zijn geen additionele maal- of mengstappen vereist tussen deeltjesvorming en compressie. Door middel van cosproeidrogen van een geneesmiddel met koolhydraten (erythritol, maltodextrine, mannitol), superdesintegrant (crospovidone), glijmiddel (colloïdaal silicium dioxide) en surfactant (polyoxyethyleen 20 sorbitan monooleaat) verbeterde de produceerbaarheid, hygroscopiciteit, vloeibaarheid en compacteerbaarheid van de geproduceerde poeders voor directe compressie in vergelijking met de individuele componenten. Door gebruik te maken van de nieuw ontwikkelde productietechniek werd het aantal processtappen gereduceerd en de productie-efficiëntie verbeterd. Tevens worden de productiekosten verminderd zodat de winst verhoogt. Daarenboven reduceert continue productie de ‘time-to-market’ (voordelen bij opschalen, betere kwaliteit), kapitaalinvesteringen, werkingskosten, vereist oppervlak en productverlies. Deze kenmerken van ‘coprocessing’ via sproeidrogen leveren talrijke duidelijke economische voordelen op voor een farmaceutische productiefaciliteit

Hot-melt co-extrusion for the production of fixed-dose combination products with a controlled release ethylcellulose matrix core

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Concomitant changes in sleep duration and body weight and body composition during weight loss and 3-mo weight maintenance

BACKGROUND: An inverse relation between sleep duration and body mass index (BMI) has been shown. OBJECTIVE: We assessed the relation between changes in sleep duration and changes in body weight and body composition during weight loss. DESIGN: A total of 98 healthy subjects (25 men), aged 20-50 y and with BMI (in kg/m2) from 28 to 35, followed a 2-mo very-low-energy diet that was followed by a 10-mo period of weight maintenance. Body weight, body composition (measured by using deuterium dilution and air-displacement plethysmography), eating behavior (measured by using a 3-factor eating questionnaire), physical activity (measured by using the validated Baecke's questionnaire), and sleep (estimate by using a questionnaire with the Epworth Sleepiness Scale) were assessed before and immediately after weight loss and 3- and 10-mo follow-ups. RESULTS: The average weight loss was 10% after 2 mo of dieting and 9% and 6% after 3- and 10-mo follow-ups, respectively. Daytime sleepiness and time to fall asleep decreased during weight loss. Short (7 to /=9 h) did not change significantly during weight loss. This change in sleep duration was concomitantly negatively correlated with the change in BMI during weight loss and after the 3-mo follow-up and with the change in fat mass after the 3-mo follow-up. CONCLUSIONS: Sleep duration benefits from weight loss or vice versa. Successful weight loss, loss of body fat, and 3-mo weight maintenance in short and average sleepers are underscored by an increase in sleep duration or vice versa. This trial was registered at clinicaltrials.gov as NCT01015508

Chronic unpredictable stress regulates visceral adipocyte-mediated glucose metabolism and inflammatory circuits in male rats

Chronic psychological stress is a prominent risk factor involved in the pathogenesis of many complex diseases, including major depression, obesity, and type II diabetes. Visceral adipose tissue is a key endocrine organ involved in the regulation of insulin action and an important component in the development of insulin resistance. Here, we examined for the first time the changes on visceral adipose tissue physiology and on adipocyte-associated insulin sensitivity and function after chronic unpredictable stress in rats. Male rats were subjected to chronic unpredictable stress for 35 days. Total body and visceral fat was measured. Cytokines and activated intracellular kinase levels were determined using high-throughput multiplex assays. Adipocyte function was assessed via tritiated glucose uptake assay. Stressed rats showed no weight gain, and their fat/lean mass ratio increased dramatically compared to control animals. Stressed rats had significantly higher mesenteric fat content and epididymal fat pad weight and demonstrated reduced serum glucose clearing capacity following glucose challenge. Alterations in fat depot size were mainly due to changes in adipocyte numbers and not size. High-throughput molecular screening in adipocytes isolated from stressed rats revealed activation of intracellular inflammatory, glucose metabolism, and MAPK networks compared to controls, as well as significantly reduced glucose uptake capacity in response to insulin stimulation. Our study identifies the adipocyte as a key regulator of the effects of chronic stress on insulin resistance, and glucose metabolism, with important ramifications in the pathophysiology of several stress-related disease states

Fast disintegrating crystalline solid dispersions of simvastatin for incorporation into orodispersible tablets

Aim : Spray dried solid dispersion (SDP) of crystalline simvastatin (SIM) in a fast disintegrating matrix of superdisintegrants was studied as a method to enhance SIM dispersibility, rheology, compactibility and compressibility for incorporation into orodispersible tablets (ODTs). Materials and Methods: The superdisintegrants investigated were crospovidone (CP), sodium starch glycollate (SSG) and calcium silicate (CS) were spray dried with simvastatin to form SDPs. Results: The SDPs were characterized and the median particle size of SDPs was similar or greater than the SIM, contributing to good rheology of SDPs, while the low bulk density of SDPs indicated a high compactibility. Interestingly electron micrographs for SDPs showed a CP or CS carrier coating of the SIM crystals, contributing to its rheology. Thermal analysis and X-ray diffraction confi rmed that SIM was crystalline in the SDPs and no interaction between SIM and any of the carrier(s) was shown by Fourier transform-infra red. Drug content analysis showed a SIM content of 90-95% in SDPs containing CP or CS, while a higher SIM content of 143% was found in SDP containing SSG. When formulated as ODTs, blend containing SIM SDPs in CP showed ease of tableting, regardless of the turret speed. In comparison, tablet blend consisting of a physical mix (PM) of SIM and CP could only be tableted at the lower turret speed of 7 rpm. ODTs formulated using SIM SDPs in CP showed a higher extent of dissolution, compared to the ODTs containing corresponding PM or the commercially available SIM Zocor® tablets (ANOVA, P \u3c 0.05). Conclusion: SDP using disintegrants as carriers may offer an alternative formulation approach for ODTs of poorly soluble drugs

Long-Range Domain Structure and Symmetry Engineering by Interfacial Oxygen Octahedral Coupling at Heterostructure Interface

In epitaxial thin film systems, the crystal structure and its symmetry deviate from the bulk counterpart due to various mechanisms such as epitaxial strain and interfacial structural coupling, which is accompanyed by a change in their properties. In perovskite materials, the crystal symmetry can be described by rotations of sixfold coordinated transition metal oxygen octahedra, which are found to be altered at interfaces. Here, it is unraveled how the local oxygen octahedral coupling at perovskite heterostructural interfaces strongly influences the domain structure and symmetry of the epitaxial films resulting in design rules to induce various structures in thin films using carefully selected combinations of substrate/buffer/film. Very interestingly it is discovered that these combinations lead to structure changes throughout the full thickness of the film. The results provide a deep insight into understanding the origin of induced structures in a perovskite heterostructure and an intelligent route to achieve unique functional properties

A deep learning approach to identify local structures in atomic-resolution transmission electron microscopy images

Recording atomic-resolution transmission electron microscopy (TEM) images is becoming increasingly routine. A new bottleneck is then analyzing this information, which often involves time-consuming manual structural identification. We have developed a deep learning-based algorithm for recognition of the local structure in TEM images, which is stable to microscope parameters and noise. The neural network is trained entirely from simulation but is capable of making reliable predictions on experimental images. We apply the method to single sheets of defected graphene, and to metallic nanoparticles on an oxide support.Comment: v2: Typo in author list correcte