Determining the Impact of Roller Compaction Processing Conditions on Granulate and API Properties: Impact of Formulation API Load.

Previous work demonstrated that roller compaction of a 40%w/w theophylline-loaded formulation resulted in granulate consisting of un-compacted fractions which were shown to constitute between 34 and 48%v/v of the granulate dependent on processing conditions. The active pharmaceutical ingredient (API) primary particle size within the un-compacted fraction was also shown to have undergone notable size reduction. The aim of the current work was to test the hypothesis that the observations may be more indicative of the relative compactability of the API due to the formulation being above the percolation threshold. This was done by assessing the impact of varied API loads in the formulation on the non-granulated fraction of the final granulate and the extent of attrition of API particles within the non-granulated fraction. The influence of processing conditions for all formulations was also investigated. The results verify that the observations, both of this study and the previous work, are not a consequence of exceeding the percolation threshold. The volume of un-compacted material within the granulate samples was observed to range between 34.7 and 65.5% depending on the API load and roll pressure, whilst the API attrition was equivalent across all conditions.

Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging.

Cognitive impairment is common following traumatic brain injury. Dopaminergic drugs can enhance cognition after traumatic brain injury, but individual responses are highly variable. This may be due to variability in dopaminergic damage between patients. We investigate whether measuring dopamine transporter levels using 123I-ioflupane single-photon emission computed tomography (SPECT) predicts response to methylphenidate, a stimulant with dopaminergic effects. Forty patients with moderate-severe traumatic brain injury and cognitive impairments completed a randomized, double-blind, placebo-controlled, crossover study. 123I-ioflupane SPECT, MRI and neuropsychological testing were performed. Patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Subjects received neuropsychological assessment after each block and completed daily home cognitive testing during the trial. The primary outcome measure was change in choice reaction time produced by methylphenidate and its relationship to stratification of patients into groups with normal and low dopamine transporter binding in the caudate. Overall, traumatic brain injury patients showed slow information processing speed. Patients with low caudate dopamine transporter binding showed improvement in response times with methylphenidate compared to placebo [median change = -16 ms; 95% confidence interval (CI): -28 to -3 ms; P = 0.02]. This represents a 27% improvement in the slowing produced by traumatic brain injury. Patients with normal dopamine transporter binding did not improve. Daily home-based choice reaction time results supported this: the low dopamine transporter group improved (median change -19 ms; 95% CI: -23 to -7 ms; P = 0.002) with no change in the normal dopamine transporter group (P = 0.50). The low dopamine transporter group also improved on self-reported and caregiver apathy assessments (P = 0.03 and P = 0.02, respectively). Both groups reported improvements in fatigue (P = 0.03 and P = 0.007). The cognitive effects of methylphenidate after traumatic brain injury were only seen in patients with low caudate dopamine transporter levels. This shows that identifying patients with a hypodopaminergic state after traumatic brain injury can help stratify the choice of cognitive enhancing therapy.

Determining the Impact of Roller Compaction Processing Conditions on Granule and API Properties.

The attrition of drug particles during the process of dry granulation, which may (or may not) be incorporated into granules, could be an important factor in determining the subsequent performance of that granulation, including key factors such as sticking to punches and bio-performance of the dosage form. It has previously been demonstrated that such attrition occurs in one common dry granulation process train; however, the fate of these comminuted particles in granules was not determined. An understanding of the phenomena of attrition and incorporation into granule will improve our ability to understand the performance of granulated systems, ultimately leading to an improvement in our ability to optimize and model the process. Unique feeding mechanisms, geometry, and milling systems of roller compaction equipment mean that attrition could be more or less substantial for any given equipment train. In this work, we examined attrition of API particles and their incorporation into granule in an equipment train from Gerteis, a commonly used equipment train for dry granulation. The results demonstrate that comminuted drug particles can exist free in post-milling blends of roller compaction equipment trains. This information can help better understand the performance of the granulations, and be incorporated into mechanistic models to optimize such processes.

Using high-frequency phosphorus monitoring for water quality management: a case study of the upper River Itchen, UK.

Increased concentrations of phosphorus (P) in riverine systems lead to eutrophication and can contribute to other environmental effects. Chalk rivers are known to be particularly sensitive to elevated P levels. We used high-frequency (daily) automatic water sampling at five distinct locations in the upper River Itchen (Hampshire, UK) between May 2016 and June 2017 to identify the main P species (including filterable reactive phosphorus, total filterable phosphorus, total phosphorus and total particulate phosphorus) present and how these varied temporally. Our filterable reactive phosphorus (considered the biologically available fraction) data were compared with the available Environment Agency total reactive phosphorus (TRP) values over the same sampling period. Over the trial, the profiles of the P fractions were complex; the major fraction was total particulate phosphorus with the mean percentage value ranging between 69 and 82% of the total P present. Sources were likely to be attributable to wash off from agricultural activities. At all sites, the FRP and Environment Agency TRP mean concentrations over the study were comparable. However, there were a number of extended time periods (1 to 2 weeks) where the mean FRP concentration (e.g. 0.62 mg L-1) exceeded the existing regulatory values (giving a poor ecological status) for this type of river. Often, these exceedances were missed by the limited regulatory monitoring procedures undertaken by the Environment Agency. There is evidence that these spikes of elevated concentrations of P may have a biological impact on benthic invertebrate (e.g. blue-winged olive mayfly) communities that exist in these ecologically sensitive chalk streams. Further research is required to assess the ecological impact of P and how this might have implications for the development of future environmental regulations.

Dopaminergic abnormalities following traumatic brain injury.

Traumatic brain injury can reduce striatal dopamine levels. The cause of this is uncertain, but is likely to be related to damage to the nigrostriatal system. We investigated the pattern of striatal dopamine abnormalities using 123I-Ioflupane single-photon emission computed tomography (SPECT) scans and their relationship to nigrostriatal damage and clinical features. We studied 42 moderate-severe traumatic brain injury patients with cognitive impairments but no motor parkinsonism signs and 20 healthy controls. 123I-Ioflupane scanning was used to assess dopamine transporter levels. Clinical scan reports were compared to quantitative dopamine transporter results. Advanced MRI methods were used to assess the nigrostriatal system, including the area through which the nigrostriatal projections pass as defined from high-resolution Human Connectome data. Detailed clinical and neuropsychological assessments were performed. Around 20% of our moderate-severe patients had clear evidence of reduced specific binding ratios for the dopamine transporter in the striatum measured using 123I-Ioflupane SPECT. The caudate was affected more consistently than other striatal regions. Dopamine transporter abnormalities were associated with reduced substantia nigra volume. In addition, diffusion MRI provided evidence of damage to the regions through which the nigrostriatal tract passes, particularly the area traversed by dopaminergic projections to the caudate. Only a small percentage of patients had evidence of macroscopic lesions in the striatum and there was no relationship between presence of lesions and dopamine transporter specific binding ratio abnormalities. There was also no relationship between reduced volume in the striatal subregions and reduced dopamine transporter specific binding ratios. Patients with low caudate dopamine transporter specific binding ratios show impaired processing speed and executive dysfunction compared to patients with normal levels. Taken together, our results suggest that the dopaminergic system is affected by a moderate-severe traumatic brain injury in a significant proportion of patients, even in the absence of clinical motor parkinsonism. Reduced dopamine transporter levels are most commonly seen in the caudate and this is likely to reflect the pattern of nigrostriatal tract damage produced by axonal injury and associated midbrain damage.

Reward and punishment enhance motor adaptation in stroke.

BACKGROUND AND OBJECTIVE: The effects of motor learning, such as motor adaptation, in stroke rehabilitation are often transient, thus mandating approaches that enhance the amount of learning and retention. Previously, we showed in young individuals that reward and punishment feedback have dissociable effects on motor adaptation, with punishment improving adaptation and reward enhancing retention. If these findings were able to generalise to patients with stroke, they would provide a way to optimise motor learning in these patients. Therefore, we tested this in 45 patients with chronic stroke allocated in three groups. METHODS: Patients performed reaching movements with their paretic arm with a robotic manipulandum. After training (day 1), day 2 involved adaptation to a novel force field. During the adaptation phase, patients received performance-based feedback according to the group they were allocated: reward, punishment or no feedback (neutral). On day 3, patients readapted to the force field but all groups now received neutral feedback. RESULTS: All patients adapted, with reward and punishment groups displaying greater adaptation and readaptation than the neutral group, irrespective of demographic, cognitive or functional differences. Remarkably, the reward and punishment groups adapted to similar degree as healthy controls. Finally, the reward group showed greater retention. CONCLUSIONS: This study provides, for the first time, evidence that reward and punishment can enhance motor adaptation in patients with stroke. Further research on reinforcement-based motor learning regimes is warranted to translate these promising results into clinical practice and improve motor rehabilitation outcomes in patients with stroke.

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines.

Does Magnetic Resonance Brain Scanning at 3.0 Tesla Pose a Hyperthermic Challenge to Term Neonates?

Next-generation 3-Tesla magnetic resonance (MR) scanners offer improved neonatal neuroimaging, but the greater associated radiofrequency radiation may increase the risk of hyperthermia. Safety data for neonatal 3-T MR scanning are lacking. We measured rectal temperatures continuously in 25 neonates undergoing 3-T brain MR imaging and observed no significant hyperthermic threat.

Pharmacokinetic modeling of multislice dynamic contrast-enhanced MRI in normal-healing radial fractures: A pilot study.

PURPOSE: To define the range of quantitative pharmacokinetic parameters in normal-healing bone with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI is an established technique for characterizing abnormal tissue microvasculature within solid tumors, but has also shown promise for assessing bone and bone marrow. MATERIALS AND METHODS: In this study ethical approval for eight patients was obtained. Inclusion criteria were an extra-articular distal radial fracture in patients aged 20-50 years which had united by 6 weeks in plaster cast. This was assessed by an experienced orthopedic surgeon. DCE-MRI was performed at 1.5T 6 weeks after initial injury. The transfer constant (K(trans) ), transfer rate (Kep ), and initial area under the curve (IAUC) values for the fracture site and adjacent marrow were obtained for each patient. RESULTS: The mean T1 , K(trans) , Kep , and IAUC at the fracture site were 1713 (standard deviation [SD] 645), 0.09 (SD 0.07), 0.17 (SD 0.17) and 4.9 (SD 4.4). The relative standard deviation (RSD) for the fracture site ranged from 0.38 to 0.97 and for the adjacent marrow ranged from 0.95-3.88. Within each patient the range of RSDs was 0.04-0.42 for T1 , 0.26-0.91 for K(trans) , 0.14-1.06 for Kep , and 0.35-0.96 for the IAUC. CONCLUSION: Pharmacokinetic measures of perfusion can be obtained from healing fractures using DCE-MRI with "excellent" intraclass correlation coefficients for inter- and intrarater reliability. The use of these perfusion parameters is limited by wide patient-to-patient variation and slice-to-slice variation within patients.

Test-retest reliability of rapid whole body and compartmental fat volume quantification on a widebore 3T MR system in normal-weight, overweight, and obese subjects.

PURPOSE: To measure the test-retest reliability of rapid (<15 min) whole body and visceral fat volume quantification in normal and obese subjects on a widebore 3T MR system and compare it with conventional manual segmentation. MATERIALS AND METHODS: Thirty participants (body mass index [BMI] 20.1-48.6 kg/m2 ) underwent two whole-body magnetic resonance imaging (MRI) examinations on a widebore 3T machine using a 2-point Dixon technique. Phase sensitive reconstruction and intensity inhomogeneity correction produced quantitative datasets of total adipose tissue (TAT), abdominal subcutaneous adipose tissue (ASAT), and visceral adipose tissue (VAT). The quantification was performed automatically using nonrigid atlas-based segmentation and compared with manual segmentation (SliceOmatic). RESULTS: The mean TAT was 31.74 L with a coefficient of variation (CV) of 0.79% and a coefficient of repeatability (CR) of 0.49 L. The ASAT was 7.92 L with a CV of 2.98% and a CR of 0.46 L. There was no significant difference in the semiautomated and manually segmented VAT (P = 0.73) but there were differences in the reliability of the two techniques. The mean semiautomated VAT was 2.56 L, CV 1.8%, and CR 0.09 L compared to the mean manually segmented VAT of 3.12 L, where the CV was 6.3% and the CR was 0.39 L. CONCLUSION: Rapid semiautomated whole body and compartmental fat volume quantification can be derived from a widebore 3T system, for a range of body sizes including obese patients, with "almost perfect" test-retest reliability. J. Magn. Reson. Imaging 2016;44:1464-1473.

Salience network integrity predicts default mode network function after traumatic brain injury.

Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)--which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae--regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control.

Movement speed is biased by prior experience.

How does the motor system choose the speed for any given movement? Many current models assume a process that finds the optimal balance between the costs of moving fast and the rewards of achieving the goal. Here, we show that such models also need to take into account a prior representation of preferred movement speed, which can be changed by prolonged practice. In a time-constrained reaching task, human participants made 25-cm reaching movements within 300, 500, 700, or 900 ms. They were then trained for 3 days to execute the movement at either the slowest (900-ms) or fastest (300-ms) speed. When retested on the 4th day, movements executed under all four time constraints were biased toward the speed of the trained movement. In addition, trial-to-trial variation in speed of the trained movement was significantly reduced. These findings are indicative of a use-dependent mechanism that biases the selection of speed. Reduced speed variability was also associated with reduced errors in movement amplitude for the fast training group, which generalized nearly fully to a new movement direction. In contrast, changes in perpendicular error were specific to the trained direction. In sum, our results suggest the existence of a relatively stable but modifiable prior of preferred movement speed that influences the choice of movement speed under a range of task constraints.

Test-retest reliability of automated whole body and compartmental muscle volume measurements on a wide bore 3T MR system.

PURPOSE: To measure the test-retest reproducibility of an automated system for quantifying whole body and compartmental muscle volumes using wide bore 3 T MRI. MATERIALS AND METHODS: Thirty volunteers stratified by body mass index underwent whole body 3 T MRI, two-point Dixon sequences, on two separate occasions. Water-fat separation was performed, with automated segmentation of whole body, torso, upper and lower leg volumes, and manually segmented lower leg muscle volumes. RESULTS: Mean automated total body muscle volume was 19·32 L (SD9·1) and 19·28 L (SD9·12) for first and second acquisitions (Intraclass correlation coefficient (ICC) = 1·0, 95% level of agreement -0·32-0·2 L). ICC for all automated test-retest muscle volumes were almost perfect (0·99-1·0) with 95% levels of agreement 1.8-6.6% of mean volume. Automated muscle volume measurements correlate closely with manual quantification (right lower leg: manual 1·68 L (2SD0·6) compared to automated 1·64 L (2SD 0·6), left lower leg: manual 1·69 L (2SD 0·64) compared to automated 1·63 L (SD0·61), correlation coefficients for automated and manual segmentation were 0·94-0·96). CONCLUSION: Fully automated whole body and compartmental muscle volume quantification can be achieved rapidly on a 3 T wide bore system with very low margins of error, excellent test-retest reliability and excellent correlation to manual segmentation in the lower leg. KEY POINTS: Sarcopaenia is an important reversible complication of a number of diseases. Manual quantification of muscle volume is time-consuming and expensive. Muscles can be imaged using in and out of phase MRI. Automated atlas-based segmentation can identify muscle groups. Automated muscle volume segmentation is reproducible and can replace manual measurements.

Petrography, stable isotope compositions, microRaman spectroscopy, and presolar components of Roberts Massif 04133: A reduced CV3 carbonaceous chondrite.

Here, we report the mineralogy, petrography, C-N-O-stable isotope compositions, degree of disorder of organic matter, and abundances of presolar components of the chondrite Roberts Massif (RBT) 04133 using a coordinated, multitechnique approach. The results of this study are inconsistent with its initial classification as a Renazzo-like carbonaceous chondrite, and strongly support RBT 04133 being a brecciated, reduced petrologic type >3.3 Vigarano-like carbonaceous (CV) chondrite. RBT 04133 shows no evidence for aqueous alteration. However, it is mildly thermally altered (up to approximately 440 °C); which is apparent in its whole-rock C and N isotopic compositions, the degree of disorder of C in insoluble organic matter, low presolar grain abundances, minor element compositions of Fe,Ni metal, chromite compositions and morphologies, and the presence of unequilibrated silicates. Sulfides within type I chondrules from RBT 04133 appear to be pre-accretionary (i.e., did not form via aqueous alteration), providing further evidence that some sulfide minerals formed prior to accretion of the CV chondrite parent body. The thin section studied contains two reduced CV3 lithologies, one of which appears to be more thermally metamorphosed, indicating that RBT 04133, like several other CV chondrites, is a breccia and thus experienced impact processing. Linear foliation of chondrules was not observed implying that RBT 04133 did not experience high velocity impacts that could lead to extensive thermal metamorphism. Presolar silicates are still present in RBT 04133, although presolar SiC grain abundances are very low, indicating that the progressive destruction or modification of presolar SiC grains begins before presolar silicate grains are completely unidentifiable.

The effect of pre-treatment and process conditions on the gas barrier properties of fibrillated cellulose films and coatings: A review.

Microfibrillated cellulose (MFC) is a bio-material produced by disintegrating cellulose fibres into fibrillar components. MFC could offer a sustainable solution to packaging needs since it can form an excellent barrier to oxygen. However, a comprehensive understanding of how MFC characteristics impact barrier properties of MFC films or coatings is required. This article critically reviews how the extent of separation of fibres into fibrils-and any resulting changes to the crystallinity and degree of polymerisation of cellulose-influences gas barrier properties of MFC films or coatings. Findings from publications investigating the barrier performance of MFC prepared through different processes intending to increase the effectiveness of fibrillation are evaluated and compared. The effects of processing conditions or chemical pre-treatments on barrier properties of MFC films or coatings are then discussed. A comparison of reported results showed that morphology and size polydispersity of the cellulose strongly influence the barrier properties of MFC. However, changing the MFC production process to decrease fibril diameter and polydispersity can result in changes to cellulose crystallinity; reduction in fibril length; introduction of bulky functional groups; or increased fibril surface charge: all of which could have a negative impact on the barrier properties of the final films or coatings.

Myocardial inflammation after elective percutaneous coronary intervention.

BACKGROUND: It is well established that inflammation plays a central role in the sequalae of percutaneous coronary intervention (PCI). Most of the studies to date have focused on the inflammatory reaction affecting the vessel wall post angioplasty. However, there are data to suggest that the main foci of inflammation are in fact in the myocardium beyond the vessel wall. The main aim of our study was to investigate the myocardial inflammation post elective, uncomplicated angioplasty with cardiovascular magnetic resonance (CMR) enhanced by ultrasmall superparamagnetic particles of iron oxide (USPIO) and also blood biomarkers. This is the first study to report such findings post elective angioplasty. METHODS: We assessed patients undergoing elective angioplasty for stable angina with USPIO-enhanced CMR two weeks later and compared the results to those of healthy volunteers utilised as a control group. We excluded patients with previous myocardial infarction, previous PCI or any significant inflammatory condition. All patients also underwent blood biomarker testing at baseline (pre-PCI), 4 hours and 2 weeks later. RESULTS: A total of five patients and three controls were scanned. There was a small absolute increase, although statistically not significant, in R2* values in the PCI area compared with either remote myocardium from same patient (PCI area (LAD) vs remote myocardium (Cx) (19.3 ± 10.8 vs 9.2±7.9, p =0.1)) or healthy myocardium from healthy volunteers (PCI area (LAD) vs healthy myocardium (LAD) (19.3 ± 10.8 vs 12.2 ± 4.0, p = 0.2)). PTX3 and IL6 were the only biomarkers that changed significantly from baseline to 4 hours to 2 weeks. Both biomarkers peaked at 4 hours. CONCLUSION: We have utilised USPIO-enhanced CMR for the first time, to assess myocardial inflammation post elective, uncomplicated PCI. We have demonstrated a small, numerical increase in inflammation which was not statistically significant. This first study opens the way for future studies to use this method as an endpoint for inflammation targeting.

The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke.

Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, in which each patient was assessed for 20 testing sessions, in three phases: pretreatment (Phase A1), on transdermal rotigotine for 7-11 days (Phase B) and post-treatment (Phase A2), with the exact duration of each phase randomized within limits. Outcome measures included performance on cancellation (visual search), line bisection, visual working memory, selective attention and sustained attention tasks, as well as measures of motor control. Sixteen right-hemisphere stroke patients were recruited, all of whom completed the trial. Performance on the Mesulam shape cancellation task improved significantly while on rotigotine, with the number of targets found on the left side increasing by 12.8% (P = 0.012) on treatment and spatial bias reducing by 8.1% (P = 0.016). This improvement in visual search was associated with an enhancement in selective attention but not on our measures of working memory or sustained attention. The positive effect of rotigotine on visual search was not associated with the degree of preservation of prefrontal cortex and occurred even in patients with significant prefrontal involvement. Rotigotine was not associated with any significant improvement in motor performance. This proof-of-concept study suggests a beneficial role of dopaminergic modulation on visual search and selective attention in patients with hemispatial neglect following stroke.

Dissociation between verbal response initiation and suppression after prefrontal lesions.

Some of the most striking symptoms after prefrontal damage are reduction of behavioral initiation and inability to suppress automatic behaviors. However, the relation between these 2 symptoms and the location of the lesions that cause them are not well understood. This study investigates the cerebral correlates of initiation and suppression abilities assessed by the Hayling Sentence Completion Test, using the human lesion approach. Forty-five patients with focal brain lesions and 110 healthy matched controls were examined. We combined a classical group approach with 2 voxel-based lesion methods. The results show several critical prefrontal regions to Hayling Test performance, associated with either common or differential impairment in "initiation" and "suppression" conditions. A crucial role for medial rostral prefrontal cortex (BA 10) in the initiation condition was shown by both group and lesion-mapping methods. A posterior inferolateral lesion provoked both initiation and suppression slowness, although to different degrees. An orbitoventral region was associated with errors in the suppression condition. These findings are important for clinical practice since they indicate that the brain regions required to perform a widely used and sensitive neuropsychological test but also shed light on the regions crucial for distinct components of adaptative behaviors, in particular, rostral prefrontal cortex.

Application of external lubrication during the roller compaction of adhesive pharmaceutical formulations.

A novel use of external lubrication has been investigated in which magnesium stearate was applied directly to the roll surface during roller compaction. A scalable parameter; travelling roll distance per shot (D(pS)), has been defined which ensures that an equal amount of magnesium stearate is applied to the roll surface per rotation at any roll speed. It was found that a formulation containing 20% w/w of either the API Pravastatin or Ibipinabant required a smaller D(pS) than a placebo formulation in order to prevent roll adherence. The inherent adhesiveness, and hence the required amount of external magnesium stearate to prevent roll adhesion, will depend on the material properties of the formulation. The amount of magnesium stearate transferred from the roll surface to the ribbon was measured using inductively coupled plasma optical emission spectroscopy and was found to be less than 0.01% w/w. This is a significant reduction in magnesium stearate compared to the normal manufacturing procedure of blending 0.25-2.0% w/w within the formulation.The advantage of external lubrication during roller compaction is the significant reduction in magnesium stearate from the formulation which could lead to the production of tablets with superior mechanical properties and faster dissolution times.