Wet granulation to overcome liquisolid technique issues of poor flowability and compactibility: A study to enhance Glibenclamide dissolution

The aim of this study is to apply wet granulation on liquisolid powders to overcome issues of poor powder flowability and compressibility especially with using high viscosity liquid vehicles. Different liquisolid formulations were made using three excipients where the effect of each excipient used in the dissolution of the model hydrophobic drug (Glibenclamide) was evaluated. The Glibenclamide tablets were formulated using PEG 400, Synperonic PE/L44 and Cremophor ELP, at a 10 %w/w in liquid vehicle drug concentration. The carrier (Avicel®PH102) was used followed by colloidal silicon dioxide (coating material) that converted the wet mixture into dry powder. Potato starch, 5%w/w, as a disintegrant was mixed with the mixture manually for 10 minutes and was finalized by adding 0.75% of magnesium stearate as a lubricant. The final powder (depending on its flowability and compactability) was then compacted automatically using a single-punch tableting machine to give tablets with 4mg unit drug dose. Prepared liquisolid compacts were characterised via B.P. quality control tests. In this study, a novel discovery was achieved to overcome the major problems with liquisolid preparations (flowability and compactability). This new technique is the wet granulation process to be applied with liquisolid powders just before the compaction stage of the powders into tablets. Consequently, it was found that by application of wet granulation to liquisolid powder admixture, the large-scale production of liquisolid compacts is feasible and can be easily applied by pharmaceutical industry. As with some liquisolid vehicles especially high viscosity although very good to enhance dissolution usually formulations are studied in powder forms [1,2]

Investigation on replacement of fish oil by vegetable oils (rice bran, soybean and linseed) in diet of rainbow trout (Oncorhynchus mykiss)

The aim of the present study was to determine the impact of replacing the fish oil by alternative lipid sources in diets for rainbow trout (Oncorhynchus mykiss) on growth, fatty acid profiles of muscle. Five isonitrogenous and isoenergetic semipurified diets were formulated containing 100% rice bran oil (RBO), 100% linseed oil (LO), 100% Soybean oil (SO) and a 1:1:1:1 rice bran, linseed, soybean and fish oil mixture (MX) were compared to a pure fish oil (FO) diet. The diets were fed to apparent satiation twice a day to triplicate groups of 30 rainbow trout with an initial weight of 90g for 15 weeks at 12°C.At the end of the experiment, fillet samples were collected from fish for the measurement of fatty acid profile and fillet composition. Fish fed the FO diet had the highest weight gain over the experimental period (280.28 g), However no differences in growth rate and CF were observed across diet groups. Feed conversion ratios (FCR) ranged from 1.12 to 1.24. Significant difference in FCR was found in the group fed an FO diet. The fillet lipid concentrations and fatty acid composition of the fish were significantly affected by the experimental diets. Fish fed the FO diet contained significantly lower lipid levels (20.18%) than those fed the 4 other diets. The highest level of n-3 PUFA concentrations were recorded in fish fed the LO diet (21.8) with significant difference than other diets and the lowest were in those fed the RBO diet (7.84). Fish fed the SO diet contained significantly higher level of n-6 PUFA concentrations (31.72) than other diets and the lowest were in those fed the FO diet (19.15). Fish on the FO diet had a significantly greater percentage of DHA (10.10%) in muscle tissue compared with fish on all other diets and the lowest was in those fed the RBO diet (2.81%). However, the highest level of eicosapentaenoic acid (EPA) concentrations was recorded in fish fed the SO diet (1.84%) and the lowest in those fed the diet (0.67%). This study showed considerable reductions (about 3-fold) in the n-3/n-6 ratio when FO in the fish diet was replaced by rice bran and soybean oils, which may be extremely negative from a nutritional point of view. In other hand linseed oil had the highest n-3/n-6 ratio (0.91) that was comparable with fish oil n- 3/n-6 ratio (0.89). The results in this study imply that an appropriate mix of vegetable oils and FO can replace the sole use of FO in fish feeds

Regional diversity in the murine cortical vascular network is revealed by synchrotron X-ray tomography and is amplified with age

Cortical bone is permeated by a system of pores, occupied by the blood supply and osteocytes. With ageing, bone mass reduction and disruption of the microstructure are associated with reduced vascular supply. Insight into the regulation of the blood supply to the bone could enhance the understanding of bone strength determinants and fracture healing. Using synchrotron radiation-based computed tomography, the distribution of vascular canals and osteocyte lacunae was assessed in murine cortical bone and the influence of age on these parameters was investigated. The tibiofibular junction from 15-week- and 10-month-old female C57BL/6J mice were imaged post-mortem. Vascular canals and three-dimensional spatial relationships between osteocyte lacunae and bone surfaces were computed for both age groups. At 15 weeks, the posterior region of the tibiofibular junction had a higher vascular canal volume density than the anterior, lateral and medial regions. Intracortical vascular networks in anterior and posterior regions were also different, with connectedness in the posterior higher than the anterior at 15 weeks. By 10 months, cortices were thinner, with cortical area fraction and vascular density reduced, but only in the posterior cortex. This provided the first evidence of age-related effects on murine bone porosity due to the location of the intracortical vasculature. Targeting the vasculature to modulate bone porosity could provide an effective way to treat degenerative bone diseases, such as osteoporosis

On the Energy Transfer Performance of Mechanical Nanoresonators Coupled with Electromagnetic Fields

We study the energy transfer performance in electrically and magnetically coupled mechanical nanoresonators. Using the resonant scattering theory, we show that magnetically coupled resonators can achieve the same energy transfer performance as for their electrically coupled counterparts, or even outperform them within the scale of interest. Magnetic and electric coupling are compared in the Nanotube Radio, a realistic example of a nano-scale mechanical resonator. The energy transfer performance is also discussed for a newly proposed bio-nanoresonator composed of a magnetosomes coated with a net of protein fibers.Comment: 9 Pages, 3 Figure

Sexually dimorphic tibia shape is linked to natural osteoarthritis in STR/Ort mice

Human osteoarthritis (OA) is detected only at late stages. Male STR/Ort mice develop knee OA spontaneously with known longitudinal trajectory, offering scope to identify OA predisposing factors. We exploit the lack of overt OA in female STR/Ort and in both sexes of parental, control CBA mice to explore whether early divergence in tibial bone mass or shape are linked to emergent OA

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Breathing disorders in congestive heart failure: gender, etiology and mortality

We investigated the relationship between sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) while awake as well as mortality. Eighty-nine consecutive outpatients (29 females) with congestive heart failure (CHF; left ventricular ejection fraction, LVEF <45%) were prospectively evaluated. The presence of SDB and of CSR while awake before sleep onset was investigated by polysomnography. SDB prevalence was 81 and 56%, using apnea-hypopnea index cutoffs >5 and >15, respectively. CHF etiologies were similar according to the prevalence of SDB and sleep pattern. Males and females were similar in age, body mass index, and LVEF. Males presented more SDB (P = 0.01), higher apnea-hypopnea index (P = 0.04), more light sleep (stages 1 and 2; P < 0.05), and less deep sleep (P < 0.001) than females. During follow-up (25 ± 10 months), 27% of the population died. Non-survivors had lower LVEF (P = 0.01), worse New York Heart Association (NYHA) functional classification (P = 0.03), and higher CSR while awake (P < 0.001) than survivors. As determined by Cox proportional model, NYHA class IV (RR = 3.95, 95%CI = 1.37-11.38, P = 0.011) and CSR while awake with a marginal significance (RR = 2.96, 95%CI = 0.94-9.33, P = 0.064) were associated with mortality. In conclusion, the prevalence of SDB and sleep pattern of patients with Chagas' disease were similar to that of patients with CHF due to other etiologies. Males presented more frequent and more severe SDB and worse sleep quality than females. The presence of CSR while awake, but not during sleep, may be associated with a poor prognosis in patients with CHF