Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability

This study investigates the use of co-melt fluidised bed granulation for the agglomeration of model pharmaceutical powders, namely, lactose mono-hydrate, PEG 10000, poly-vinyl pyrolidone and ibuprofen as a model drug. Granulation within the co-melt system was found to follow a nucleationâ??steady growthâ??coating regime profile. Using high molecular weight PEG binder, the granulation mechanism and thus the extent of granulation was found to be significantly influenced by binder viscosity. The compression properties of the granulate within the hot fluidised bed were correlated using a novel high temperature experimental procedure. It was found that the fracture stress and fractural modulus of the materials under hot processing conditions were orders of magnitude lower than those measured under ambient conditions. A range of particle velocities within the granulator were considered based on theoretical models. After an initial period of nucleation, the Stokes deformation number analysis indicated that only velocities within the high shear region of the fluidised bed were sufficient to promote significant granule deformation and therefore, coalescence. The data also indicated that larger granules de-fluidised preventing agglomeration by coalescence. Furthermore, experimental data indicated that dissipation of the viscous molten binder to the surface was the most important factor in the latter stages of the granulation process. From a pharmaceutical perspective the inclusion of the model drug, ibuprofen, combined with PVP in the co-melt process proved to be highly significant. It was found that using DSC analysis on the formulations that the decrease in the heat of fusion associated with the melting of ibuprofen within the FHMG systems may be attributed to interaction between PVP and ibuprofen through inter-molecular hydrogen bonding. This interaction decreases the crystallinity of ibuprofen and facilitates solubilisation and bioavailability within the solid matrix.

Do Total and High Density Lipoprotein Cholesterol and Triglycerides Act Independently in the Prediction of Ischemic Heart Disease? Ten-Year Follow-Up of Caerphilly and Speedwell Cohorts

Several studies have suggested that men with raised plasma triglycerides (TGs) in combination with adverse levels of other lipids may be at special risk of subsequent ischemic heart disease (IHD). We examined the independent and combined effects of plasma lipids at 10 years of follow-up. We measured fasting TGs, total cholesterol (TC), and high density lipoprotein cholesterol (HDLC) in 4362 men (aged 45 to 63 years) from 2 study populations and reexamined them at intervals during a 10-year follow-up. Major IHD events (death from IHD, clinical myocardial infarction, or ECG-defined myocardial infarction) were recorded. Five hundred thirty-three major IHD events occurred. All 3 lipids were strongly and independently predictive of IHD after 10 years of follow-up. Subjects were then divided into 27 groups (ie, 33) by the tertiles of TGs, TC, and HDLC. The number of events observed in each group was compared with that predicted by a logistic regression model, which included terms for the 3 lipids (without interactions) and potential confounding variables. The incidence of IHD was 22.6% in the group with the lipid risk factor combination with the highest expected risk (high TGs, high TC, and low HDLC) and 4.7% in the group with the lowest expected risk (P

Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism

A side-effect of treatment with antipsychotic drugs for schizophrenia is increased body fat, which leads to further morbidity and poor adherence to treatment. The 5-hydroxytryptamine 2C receptor (5-HT2C) has been associated with this effect; we aimed to establish whether a genetic polymorphism of the promoter region of this receptor affects weight gain after drug treatment in first-episode patients with schizophrenia. We noted significantly less weight gain in patients with the -759T variant allele (p=0.0003) than in those without this allele, who were more likely to have substantial (>7%) weight gain (p=0.002). We have identified a genetic factor that is associated with antipsychotic drug-induced weight gain.