Demonstration of pharmaceutical tablet coating process by injection molding technology

We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300?μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets.     

Second generation antipsychotic-induced mitochondrial alterations: Implications for increased risk of metabolic syndrome in patients with schizophrenia

Metabolic syndrome (MetS) is seen more frequently in persons with schizophrenia than in the general population, and these metabolic abnormalities are further aggravated by second generation antipsychotic (SGA) drugs. Although the underlying mechanisms responsible for the increased prevalence of MetS among patients under SGA treatment are not well understood, alterations in mitochondria function have been implicated. We performed a comprehensive evaluation of the role of mitochondrial dysfunction in the pathophysiology of drug-induced MetS in schizophrenia. We found a downregulation in genes encoding subunits of the electron transport chain complexes (ETC), enzyme activity, and mitochondrial dynamics in peripheral blood cells from patients at high-risk for MetS. Additionally, we evaluated several markers of energy metabolism in lymphoblastoid cell lines from patients with schizophrenia and controls following exposure to antipsychotics. We found that the high-risk drugs clozapine and olanzapine induced a general down-regulation of genes involved in the ETC, as well as decreased activities of the corresponding enzymes, ATP levels and a significant decrease in all the functional parameters of mitochondrial oxygen consumption in cells from patients and controls. We also observed that the medium-risk SGA quetiapine decreased oxygen consumption and respiratory control ratio in controls and patients. Additionally, clozapine and olanzapine induced a downregulation of Drp1 and Mfn2 both in terms of mRNA and protein levels. Together, these data suggest that an intrinsic defect in multiple components of oxidative metabolism may contribute to the increased prevalence of MetS in patients under treatment with SGAs known to cause risk for MetS.     

Alcohol-related affordances and group subjectivities: A Q-Methodology study

Aims: An Ecological approach to alcohol behaviour focuses on understanding individual–environment transactions, rather than on cognitive antecedents of behaviour. Meaning exists in the interdependence of individuals and their environments, in terms of affordances. Through subjective experience, this study focussed on group viewpoints related to alcohol-related affordances, or opportunities to consume alcohol in shared drinking environments. Methods: Forty students with a range of self-reported drinking behaviours participated in a Q-Methodology study, ranking 60 statements along a symmetrical grid. This varied concourse of alcohol-related affordances was obtained from a previous observation study within licenced premises and a photo-elicitation interview study with drinkers. Findings: Factor analysis and post-sort interviews revealed four subjective perspectives held by groups about their drinking behaviour: 13 participants were aware of contextual influences, but autonomous in their drinking choices; 12 participants were conscious of influences and compliant to their effects; six participants were unaware of influences, but unanimous with their peers; two participants were concerned about acting appropriately in a context by taking up canonical affordances. Conclusions: Grouping subjectivities from a varied concourse of affordances can reveal subjective experience in relation to drinking environments and alcohol behaviour. This conceptual approach for understanding drinking behaviour should be studied further.     

I Am Quite Mellow But I Wouldn't Say Everyone Else Is”: How UK Students Compare Their Drinking Behavior to Their Peers'

Background: Excessive drinking is commonplace at UK Universities. Individuals may misperceive how much they drink compared to others and are less likely to think that they will suffer adverse consequences. Young people often distance themselves and their friends from ‘problem drinkers’. Objectives: The aim of the study was to explore how student drinkers compared their own drinking behaviors to the drinking behaviors of others. Methods: An online survey was completed by 416 students aged 18–30 (68.5% female). They were asked ‘how do you think your drinking compares with other people like you?' and ‘how do you think your behavior when you drink compares with other people like you?’ Answers were subjected to thematic analysis. Results: The first main theme was about ‘identification as a ‘good’ drinker’. Participants suggested their own behavior when drinking was similar to their sober behavior. Further, they viewed themselves as more able to maintain a balance between staying in control and having fun while drinking. The second main theme was about ‘distancing from being a ‘bad’ drinker. Participants distanced themselves from negative prototypical drinkers, such compulsive or anti-social drinkers. They also attributed their own drinking behaviors to situational factors, but described other people as intentionally violent or aggressive. Conclusions/Importance: These findings may explain the failure of some health messages to change drinking behaviors. If drinkers perceive that their behavior when they drink is better than other people's then they may discount intervention messages. Targeting these biases could be incorporated into future interventions.     

Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals

Pharmaceuticals are ubiquitous in the natural environment with concentrations expected to rise as human population increases. Environmental risk assessments are available for a small portion of pharmaceuticals in use, raising concerns over the potential risks posed by other drugs that have little or no data. With >1900 active pharmaceutical ingredients in use, it would be a major task to test all of the compounds with little or no data. Desk-based prioritization studies provide a potential solution by identifying those substances that are likely to pose the greatest risk to the environment and which, therefore, need to be considered a priority for further study. The aim of this review was to (1) provide an overview of different prioritization exercises performed for pharmaceuticals in the environment and the results obtained; and (2) propose a new holistic risk-based prioritization framework for drugs in the environment. The suggested models to underpin this framework are discussed in terms of validity and applicability. The availability of data required to run the models was assessed and data gaps identified. The implementation of this framework may harmonize pharmaceutical prioritization efforts and ensure that, in the future, experimental resources are focused on molecules, endpoints, and environmental compartments that are biologically relevant.