Memory for own behaviour in pinnipeds.

Pinnipeds are aquatic predators feeding on a vast range of prey, and their social behaviour differs greatly between species (from extreme polygyny in some sea lions to monogamy in some true seals). It has been hypothesised that the foraging and social complexity of their lifestyle should drive the evolution of their cognitive abilities. To investigate how aware pinnipeds are of their own behaviour, a grey seal (Halichoerus grypus), two harbour seals (Phoca vitulina) and four South American sea lions (Otaria flavescens) were trained to repeat their own behaviour on command. Three already trained behaviours were used, and the animal was asked to repeat the behaviour twice to ensure that the animal recalled its own behaviour and not the command given for the previous behaviour. All three species could recall their own behaviour significantly better than by chance. The duration for which the animals could recall their behaviour was tested using a staircase paradigm. A delay was implemented between the completion of the behaviour and the command to repeat it. The delay was increased after correct responses and decreased after incorrect responses. The performance of all species fell towards chance level after 12-18 s, with no significant difference between species. These results indicate that sea lions and true seals are aware of their own behaviour and that true seals have similar short-term memory abilities. It also shows that pinnipeds have less developed short-term memory abilities compared to other aquatic predators, such as the bottlenose dolphin. The complexity of pinniped foraging and social behaviour does not seem to have driven the evolution of short-term memory abilities in these animals but might have contributed to their ability to recall their own behaviour.

The use of seal scarers as a protective mitigation measure can induce hearing impairment in harbour porpoises.

Acoustic deterrent devices (ADDs) are used to deter seals from aquacultures but exposure of harbour porpoises (Phocoena phocoena) occurs as a side-effect. At construction sites, by contrast, ADDs are used to deter harbour porpoises from the zone in which pile driving noise can induce temporary threshold shifts (TTSs). ADDs emit such high pressure levels that there is concern that ADDs themselves may induce a TTS. A harbour porpoise in human care was exposed to an artificial ADD signal with a peak frequency of 14 kHz. A significant TTS was found, measured by auditory evoked potentials, with an onset of 142 dB re 1 µPa2s at 20 kHz and 147 dB re 1 µPa2s at 28 kHz. The authors therefore strongly recommend to gradually increase and down regulate source levels of ADDs to the desired deterrence range. However, further research is needed to develop a reliable relationship between received levels and deterrence.

Drivers of the dive response in pinnipeds; apnea, submergence or temperature?

Long and deep dives in marine mammals are enabled by high mass-specific oxygen stores and the dive response, which reduces oxygen consumption in concert with increased peripheral vasoconstriction and a lowered heart rate during dives. Diving heart rates of pinnipeds are highly variable and modulated by many factors, such as breath holding (apnea), pressure, swimming activity, temperature and even cognitive control. However, the individual effects of these factors on diving heart rate are poorly understood because of the difficulty of parsing their relative contributions in diving pinnipeds. Here, we examined the effects of apnea and external sensory inputs as autonomic drivers of bradycardia. Specifically, we hypothesized that (1) water stimulation of facial receptors would - as is the case for terrestrial mammals - enhance the dive response, (2) increasing the facial area stimulated would lead to a more intense bradycardia, and (3) cold water would elicit a more pronounced bradycardia than warm water. Three harbor seals (Phoca vitulina) and a California sea lion (Zalophus californianus) were trained to breath hold in air and with their heads submerged in a basin with variable water level and temperature. We show that bradycardia occurs during apnea without immersion. We also demonstrate that bradycardia is strengthened by both increasing the area of facial submersion and colder water. Thus, we conclude that the initiation of the dive response in pinnipeds is more strongly related to breath holding than in terrestrial mammals, but the degree of the dive response is potentiated autonomically via stimulation of facial mechano- and thermo-receptors upon submergence.

High field metabolic rates of wild harbour porpoises.

Reliable estimates of field metabolic rates (FMRs) in wild animals are essential for quantifying their ecological roles, as well as for evaluating fitness consequences of anthropogenic disturbances. Yet, standard methods for measuring FMR are difficult to use on free-ranging cetaceans whose FMR may deviate substantially from scaling predictions using terrestrial mammals. Harbour porpoises (Phocoena phocoena) are among the smallest marine mammals, and yet they live in cold, high-latitude waters where their high surface-to-volume ratio suggests high FMRs to stay warm. However, published FMR estimates of harbour porpoises are contradictory, with some studies claiming high FMRs and others concluding that the energetic requirements of porpoises resemble those of similar-sized terrestrial mammals. Here, we address this controversy using data from a combination of captive and wild porpoises to estimate the FMR of wild porpoises. We show that FMRs of harbour porpoises are up to two times greater than for similar-sized terrestrial mammals, supporting the hypothesis that small, carnivorous marine mammals in cold water have elevated FMRs. Despite the potential cost of thermoregulation in colder water, harbour porpoise FMRs are stable over seasonally changing water temperatures. Varying heat loss seems to be managed via cyclical fluctuations in energy intake, which serve to build up a blubber layer that largely offsets the extra costs of thermoregulation during winter. Such high FMRs are consistent with the recently reported high feeding rates of wild porpoises and highlight concerns about the potential impact of human activities on individual fitness and population dynamics.

Precocious hearing in harbour porpoise neonates.

Hearing is the primary sensory modality for toothed whales, but it is not known at which age it is fully developed. For newborn calves, hearing could fill an important function in maintaining contact with the mother and to develop echolocation skills. We non-invasively measured the auditory brainstem response (ABR) in two neonate (age 1-4 days) and three adult harbour porpoises (Phocoena phocoena). The stimuli consisted of clicks centred at 130 kHz, which is within the frequency band used for echolocation and communication in this species. The temporal pattern of the neonate ABRs was indistinguishable to the adult ones. There were no significant differences between calves and adults regarding hearing thresholds and ABR latencies. The ABR amplitudes were up to more than an order of magnitude larger in newborns than in adults, most likely due to the neonates' smaller size. These results indicate that hearing is fully developed within a day after birth, which suggests that harbour porpoise neonates have the earliest hearing development of any mammal studied so far. This may be explained by the evolutionary pressures imposed by the aquatic environment for a rapid development of the key sensory system in harbour porpoises.

Kolliphor surfactants affect solubilization and bioavailability of fenofibrate. Studies of in vitro digestion and absorption in rats.

Selection of excipients for drug formulations requires both intellectual and experimental considerations as many of the used excipients are affected by physiological factors, e.g., they may be digested by pancreatic enzymes in the gastrointestinal tract. In the present paper we have looked systematically into the differences between Kolliphor ELP, EL, and RH40 and how they affect the bioavailability of fenofibrate, through pharmacokinetic studies in rats and in vitro lipolysis studies. The study design was made as simple as possible to avoid confounding factors, for which reason the tested formulations only comprised an aqueous micellar solution of the model drug (fenofibrate) in varying concentrations (2-25% (w/v)) of the three tested surfactants. Increased concentrations of Kolliphor ELP and EL led to increased fenofibrate AUC0-24h values. For the Kolliphor RH40 formulations, an apparent fenofibrate absorption optimum was seen at 15% (w/v) surfactant, displaying both the highest AUC0-24h and Cmax. The reduced absorption of fenofibrate from the formulation containing the highest level of surfactant (25% w/v) was thought to be caused by some degree of trapping within Kolliphor RH40 micelles. In vitro, Kolliphor ELP and EL were found to be more prone to digestion than Kolliphor RH40, though not affecting the in vivo results. The highest fenofibrate bioavailability was attained from formulations with high Kolliphor ELP/EL levels (25% (w/v)), indicating that these surfactants are the better choice for solubilizing fenofibrate in order to increase the absorption upon oral administration. Due to drug dependent effects of the different types of Kolliphor, more studies are recommended in order to understand which type of Kolliphor is best suited for a given drug.

Pharmaceutical microparticle engineering with electrospraying: the role of mixed solvent systems in particle formation and characteristics.

Microparticles of Celecoxib, dispersed in a matrix of poly(lactic-co-glycolic acid) (PLGA), were prepared by electrospraying using different solvent mixtures to investigate the influence upon particle formation and the resulting particle characteristics. Mixtures consisting of a good solvent, acetone, and an anti-solvent, methanol, for PLGA were studied in different ratios. Properties of the spraying solutions were examined and the resulting microparticles were characterized with regard to size, morphology, porosity, solid state form, surface chemistry and drug release. Particle formation was strongly influenced by the polymer molecular conformation during droplet formation and by the anti-solvent concentration during droplet drying. A strong correlation was found between particle morphology and the solubility of the polymer in the solvent mixtures. The lack of chain entanglements in droplets containing anti-solvent resulted in compact polymer conformation and grain-like particle morphology. Further, the early precipitation of polymer and low chain interaction with increasing content of anti-solvent resulted in surface enrichment of drug (from 10 and 20% up to 41 and 57% respectively), also demonstrated by the increasingly higher drug release rates. The results demonstrate the importance of solvent composition in particle preparation and indicate potential for exploiting this dependence to improve pharmaceutical particle design and performance.

Evaluation of immune and stress status in harbour porpoises (Phocoena phocoena): can hormones and mRNA expression levels serve as indicators to assess stress?

BACKGROUND: The harbour porpoise is exposed to increasing pressure caused by anthropogenic activities in its marine environment. Numerous offshore wind farms are planned or under construction in the North and Baltic Seas, which will increase underwater noise during both construction and operation. A better understanding of how anthropogenic impacts affect the behaviour, health, endocrinology, immunology and physiology of the animals is thus needed. The present study compares levels of stress hormones and mRNA expression of cytokines and acute-phase proteins in blood samples of harbour porpoises exposed to different levels of stress during handling, in rehabilitation or permanent human care.Free-ranging harbour porpoises, incidentally caught in pound nets in Denmark, were compared to harbour porpoises in rehabilitation at SOS Dolfijn in Harderwijk, the Netherlands, and individuals permanently kept in human care in the Dolfinarium Harderwijk and Fjord & Belt Kerteminde, Denmark. Blood samples were investigated for catecholamines, adrenaline, noradrenaline and dopamine, as well as for adrenocorticotropic hormone (ACTH), cortisol, metanephrine and normetanephrine. mRNA expression levels of relevant cell mediators (cytokines IL-10 and TNFα, acute-phase proteins haptoglobin and C-reactive protein and the heat shock protein HSP70) were measured using real-time PCR. RESULTS: Biomarker expression levels varied between free-ranging animals and porpoises in human care. Hormone and cytokine ranges showed correlations to each other and to the health status of investigated harbour porpoises. Hormone concentrations were higher in free-ranging harbour porpoises than in animals in human care. Adrenaline can be used as a parameter for the initial reaction to acute stress situations; noradrenaline, dopamine, ACTH and cortisol are more likely indicators for the following minutes of acute stress. There is evidence for different correlations between production of normetanephrine, metanephrine, cortisol and the expression of IL-10, HSP70 and haptoglobin. CONCLUSIONS: The expression patterns of the selected molecular biomarkers of the immune system are promising to reflect the health and immune status of the harbour porpoise under different levels of stress.

Energy expenditure and changes in body composition during exercise-based rehabilitation.

INTRODUCTION: Exercise-based rehabilitation programmes have formed the cornerstone of the treatment currently delivered at the Defence Medical Rehabilitation Centre (DMRC) based at Headley Court.Increased operational activity in recent years has meant a concomitant increase in the pressure on Defence rehabilitation resources and a greater need for effective rehabilitation strategies. The aim of this research was to assess the effects of exercise-based rehabilitation on energy expenditure and body composition. METHODS: A group of nine male volunteers (30±2.4 years) serving with the Armed Forces and suffering from a variety of musculoskeletal lower limb injuries underwent 17 days of exercise-based rehabilitation. Total daily energy expenditure (TEE) was assessed using a portable combined heart rate monitor/accelerometer (Actiheart).Changes in body composition were assessed using dual energy x-ray absorptiometry (DEXA). RESULTS: MeanTEE over the entire admission period was 2915±53 kcal/day with no significant difference in TEE observed between training week 1 (W1) and 2 (W2). However, a strong trend towards increased TEE in W1 was observed (p=0.06). No significant change was observed in fat mass (FM), lean body mass (LBM) or body-fat percentage despite the exercise-based rehabilitation programme. CONCLUSIONS: These results suggest that 17 days of exercise-based rehabilitation is insufficient to observe significant changes in body composition, despite high energy expenditure.

A comparison of two 3-week resistance training programmes commonly used in short-term military rehabilitation.

INTRODUCTION: Resistance training is an important component of rehabilitation due to its ability to increase muscular strength and enhance functional ability. The aim of this study was to assess the effects of two different resistance-training programmes currently used in military rehabilitation. METHOD: 27 male rehabilitation patients, serving with the Armed Forces and suffering from a range of lower limb musculoskeletal injuries were divided into two matched groups. Group 1 (n=14) performed the Daily Adjusted Progressive Resistance Exercise (DAPRE), whereas Group 2 (n=13) performed the Functional Strength Training (FST). An 8 repetition maximum (8RM) deadlift and countermovement vertical jump (CMVJ) test were used as Functional Assessment Tests (FATs) and as measures of changes in strength and power, respectively. Both were conducted on admission and at discharge. RESULTS: Lower limb strength and power increased significantly in both the DAPRE (p≤0.001/p≤0.001) and the FST (p≤0.001/0.001) groups. There was no significant difference between groups for either strength (p≥0.05) or power (p≥0.05). CONCLUSIONS: Short-term resistance training during rehabilitation can lead to gains in strength and power despite differences in programme design. However we conclude that three weeks of resistance training is insufficient duration to see significant differences between different training protocols.

Keeping returns optimal: gain control exerted through sensitivity adjustments in the harbour porpoise auditory system.

Animals that use echolocation (biosonar) listen to acoustic signals with a large range of intensities, because echo levels vary with the fourth power of the animal's distance to the target. In man-made sonar, engineers apply automatic gain control to stabilize the echo energy levels, thereby rendering them independent of distance to the target. Both toothed whales and bats vary the level of their echolocation clicks to compensate for the distance-related energy loss. By monitoring the auditory brainstem response (ABR) during a psychophysical task, we found that a harbour porpoise (Phocoena phocoena), in addition to adjusting the sound level of the outgoing signals up to 5.4 dB, also reduces its ABR threshold by 6 dB when the target distance doubles. This self-induced threshold shift increases the dynamic range of the biosonar system and compensates for half of the variation of energy that is caused by changes in the distance to the target. In combination with an increased source level as a function of target range, this helps the porpoise to maintain a stable echo-evoked ABR amplitude irrespective of target range, and is therefore probably an important tool enabling porpoises to efficiently analyse and classify received echoes.

Use of a goal setting intervention to increase adherence to low back pain rehabilitation: a randomized controlled trial.

OBJECTIVE: To examine the effects of a goal setting intervention on self-efficacy, treatment efficacy, adherence and treatment outcome in patients undergoing low back pain rehabilitation. DESIGN: A mixed-model 2 (time) × 3 (group) randomized controlled trial. SETTING: A residential rehabilitation centre for military personnel. SUBJECTS: UK military personnel volunteers (N = 48); mean age was 32.9 (SD 7.9) with a diagnosis of non-specific low back pain. INTERVENTIONS: Subjects were randomly assigned to either a goal setting experimental group (Exp, n = 16), therapist-led exercise therapy group (C1, n = 16) or non-therapist-led exercise therapy group (C2, n = 16). Treatment duration for all groups was three weeks. MAIN MEASURES: Self-efficacy, treatment efficacy and treatment outcome were recorded before and after the treatment period. Adherence was rated during regularly scheduled treatment sessions using the Sports Injury Rehabilitation Adherence Scale (SIRAS). The Biering-Sørensen test was used as the primary measure of treatment outcome. RESULTS: ANCOVA results showed that adherence scores were significantly higher in the experimental group (13.70 ± 1.58) compared with C2 (11.74 ± 1.35), (P < 0.025). There was no significant difference for adherence between the experimental group and C1 (P = 0.13). Self-efficacy was significantly higher in the experimental group compared to both C1 and C2 (P < 0.05), whereas no significant difference was found for treatment efficacy. Treatment outcome did not differ significantly between the experimental and two control groups. CONCLUSIONS: The findings provide partial support for the use of goal setting to enhance adherence in clinical rehabilitation.

Resistance training in musculoskeletal rehabilitation: a systematic review.

OBJECTIVE: To review the efficacy of resistance training (RT) as a therapeutic modality in various musculoskeletal conditions. DESIGN: Systematic review. SUBJECTS: Data from 1545 rehabilitation patients who had participated in structured RT programmes were included into the review. The total number of patients was composed of separate musculoskeletal conditions-chronic low back pain (CLBP) (549), tendinopathy (299), knee osteoarthritis (433), anterior cruciate ligament reconstruction (189) and hip replacement surgery (75). RESULTS: Evidence suggests that RT can increase muscle strength, reduce pain and improve functional ability in patients suffering from CLBP, knee osteoarthritis, and chronic tendinopathy and those under recovery after hip replacement surgery. CONCLUSION: RT can be used successfully as a therapeutic modality in several musculoskeletal conditions, especially those of a chronic variety. Although the exact application of training intensity and volume for maximal therapeutic effects is still unclear, it appears that RT guidelines, which have proven effective in a healthy population, can also be successfully applied in a rehabilitation context.

Haematology and clinical blood chemistry in harbour porpoises (Phocoena phocoena) from the inner Danish waters.

Harbour porpoises (Phocoena phocoena) in the Baltic Sea are under increasing pressure from anthropogenic activities, which affect the overall health of populations. Individuals' haematologic and biochemistry parameters are known to be linked to a population's health status and are therefore useful tools for cross-population comparisons and to assess health patterns of a population through time. However, it is often difficult to acquire data representing the full range of values and assess the influence of intrinsic and extrinsic factors. Here, we present the range of haematology and blood chemistry values obtained from 46 wild (n = 54 blood samples) individuals incidentally caught in pound-nets and five porpoises in long-term human care (n = 449 blood samples) from an outdoor semi-open facility in Denmark. Although it was not possible to formally test the differences between samples from free-ranging and captive individuals, lymphocyte values were lower for free-ranging animals whereas eosinophils and white blood cell values were higher in captive individuals. Aspartate aminotransferase and alanin aminotransferase values were also lower for captive individuals compared to free-ranging ones. Age group did not influence any of the blood parameters tested for free-ranging individuals. Sodium values were higher for males compared to females. Values were higher and lower in the fall for platelets and lactic acid dehydrogenase, respectively, compared to the other seasons. Based on samples yielded by individuals in long-term human care, haemoglobin, mean cell volume, white blood cells, absolute lymphocyte count, and alkaline phosphatase values were all influenced by health status based on clinical examination. These are therefore candidate parameters to assess health status of wild porpoises. Our results underline that it is essential to obtain ranges of reference values for all haematologic and biochemistry markers in order to assess health status of free-ranging individuals. Individuals in human care provide the opportunity to observe biological and ecological determinates (e.g. age, season) of long-term biomarker response patterns and to assess the suite of biomarkers best suited to predict individual health status.

Acoustic behaviour of echolocating porpoises during prey capture.

Porpoise echolocation has been studied previously, mainly in target detection experiments using stationed animals and steel sphere targets, but little is known about the acoustic behaviour of free-swimming porpoises echolocating for prey. Here, we used small onboard sound and orientation recording tags to study the echolocation behaviour of free-swimming trained porpoises as they caught dead, freely drifting fish. We analysed porpoise echolocation behaviour leading up to and following prey capture events, including variability in echolocation in response to vision restriction, prey species, and individual porpoise tested. The porpoises produced echolocation clicks as they searched for the fish, followed by fast-repetition-rate clicks (echolocation buzzes) when acquiring prey. During buzzes, which usually began when porpoises were about 1-2 body lengths from prey, tag-recorded click levels decreased by about 10 dB, click rates increased to over 300 clicks per second, and variability in body orientation (roll) increased. Buzzes generally continued beyond the first contact with the fish, and often extended until or after the end of prey handling. This unexplained continuation of buzzes after prey capture raises questions about the function of buzzes, suggesting that in addition to providing detailed information on target location during the capture, they may serve additional purposes such as the relocation of potentially escaping prey. We conclude that porpoises display the same overall acoustic prey capture behaviour seen in larger toothed whales in the wild, albeit at a faster pace, clicking slowly during search and approach phases and buzzing during prey capture.

Antifouling enzymes and the biochemistry of marine settlement.

Antifouling coatings are used extensively on marine vessels and constructions, but unfortunately they are found to pose a threat to the marine environment, notably due to content of metal-based biocides. Enzymes have repeatedly been proposed as an alternative to traditional antifouling compounds. In this review, the enzymes claimed to hold antifouling activity are classified according to catalytic functions. The enzyme functions are juxtaposed with the current knowledge about the chemistry of settlement and adhesion of fouling organisms. Specific focus will be on bacteria, microalgae, invertebrate larvae and macroalgae zoospores. Two main concepts in enzyme-based antifouling are identified: breakdown of adhesive components and catalytic production of repellent compounds in-situ. The validity of the various modes of action is evaluated and the groups of enzymes with the highest potential are highlighted.

Parsimonious data: How a single Facebook like predicts voting behavior in multiparty systems.

This study shows how liking politicians' public Facebook posts can be used as an accurate measure for predicting present-day voter intention in a multiparty system. We highlight that a few, but selective digital traces produce prediction accuracies that are on par or even greater than most current approaches based upon bigger and broader datasets. Combining the online and offline, we connect a subsample of surveyed respondents to their public Facebook activity and apply machine learning classifiers to explore the link between their political liking behaviour and actual voting intention. Through this work, we show that even a single selective Facebook like can reveal as much about political voter intention as hundreds of heterogeneous likes. Further, by including the entire political like history of the respondents, our model reaches prediction accuracies above previous multiparty studies (60-70%). The main contribution of this paper is to show how public like-activity on Facebook allows political profiling of individual users in a multiparty system with accuracies above previous studies. Beside increased accuracies, the paper shows how such parsimonious measures allows us to generalize our findings to the entire population of a country and even across national borders, to other political multiparty systems. The approach in this study relies on data that are publicly available, and the simple setup we propose can with some limitations, be generalized to millions of users in other multiparty systems.

Distribution of the UV filter 3-benzylidene camphor in rat following topical application.

A straightforward analytical method for determination of 3-benzylidene camphor (3-BC) in rat adipose tissue, brain, liver, muscle, plasma and testis following topical application was developed and validated. Three exposure levels (60, 180 and 540 mg kg(-1) day(-1)) were tested for 65 days in male Sprague-Dawley rats (24 days postnatal). Sample preparation involving homogenization and n-heptane or methanol extraction of the tissue was applied before injection into the LC-ESI-MS-MS system. The response was linear from 2 to 100 microg l(-1) for the qualifier and the quantifier MRM transitions (R(2) (quantifier) > 0.994). Detection limit of the method corresponded to 0.005 microg g(-1) tissue and 12.5 microg l(-1) plasma, respectively. Recovery was determined for all tissues (adipose tissue: 40%; all other tissues: 80-100%) at three individual levels. 3-(4-Methyl benzylidene camphor) (4-MBC) was used throughout the study as internal standard. 3-Benzylidene camphor was detected in all tissues at all exposure levels at concentrations between 0.05 microg g(-1) (liver) and 36 microg g(-1) (adipose tissue) and in plasma at 16-89 microg l(-1). The method allowed for the quantification of 3-benzylidene camphor in all tested tissues following topical application. Furthermore, it was shown that 3-benzylidene camphor can be found in various tissues in the rat following topical application. These findings may suggest that following use of 3-benzylidene camphor containing sunscreen, similar disposition and distribution may occur in humans.

Investigation of a 2-step agglomeration process performed in a rotary processor using polyethylene glycol solutions as the primary binder liquid.

The purpose of this research was to investigate the use of polyethylene glycol (PEG) solutions as the primary binder liquid in a 2-step agglomeration process performed in a rotary processor and characterize the resulting granules and their tableting characteristics. This was done by granulation of binary mixtures of microcrystalline cellulose (MCC) and either lactose, calcium phosphate, acetaminophen, or theophylline, in a 1:3 ratio, using a 50% (wt/wt) aqueous solution of PEG and water as the binder liquid. Formulations containing lactose were agglomerated using 5 different amounts of the PEG binder solution, giving rise to a PEG content in the range of 6% to 43% (wt/wt). The process outcome was characterized according to adhesion, yield, and water requirement, and the prepared granules were characterized according to size, size distribution, and flow properties as well as tableting properties. The agglomeration of all mixtures resulted in high yields of free-flowing agglomerates and gave rise to good reproducibility of the investigated agglomerate characteristics. The process allowed for the incorporation of 42.5% (wt/wt) PEG, which is higher than the percentage of PEG reported for other equipment. Tablets of sufficient strength could be prepared with all investigated excipients using 20% wt/wt PEG; higher PEG contents gave rise to adhesion and prolonged disintegration. In conclusion, agglomeration in a torque-controlled rotary processor using solutions of PEG as the primary binder liquid was found to be a robust process, suitable for the incorporation of high contents of PEG and/or drug compounds.

Wet granulation in rotary processor and fluid bed: Comparison of granule and tablet properties.

The aim of the present study was to investigate and compare granule and tablet properties of granules prepared by wet granulation in a rotary processor or a conventional fluid bed. For this purpose the working range of selected process variables was determined and a factorial study with 3 factors (equipment type, filler type, and liquid addition rate) and 1 covariate (fluidizing air flow rate) was performed. Two grades of calcium carbonate with different size and shape characteristics were applied, and the liquid addition and fluidizing air flow rates were investigated in the widest possible range. Dry mixtures of microcrystalline cellulose, polyvinyl povidone, calcium carbonate, and riboflavin, in a 10∶5∶84∶1 ratio, were granulated in both types of equipment. The granulation end point was determined manually in the fluid bed and by torque measurements in the rotary processor. The filler type had a more pronounced effect on granular properties in the fluid bed, but the rotary processor showed a higher dependency on the investigated process variables. The rotary processor gave rise to more dense granules with better flow properties, but the fluid bed granules had slightly better compressional properties. Furthermore, the distribution of a low-dose drug was found to be more homogeneous in the rotary processor granules and tablets. Generally, wet granulation in a rotary processor was found to be a good alternative to conventional fluid bed granulation, especially when cohesive powders with poor flow properties or formulations with low drug content are to be granulated by a fluidizing air technique.