RESUMO
Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration site and time was investigated using magnetic resonance imaging (MRI) in combination with a salivary tracer technique. As capsule shells, Vcaps® HPMC capsules, Vcaps® Plus HPMC capsules, gelatin and DRcaps® designed release capsules were used. The three HPMC-based capsules (Vcaps®, Vcaps® Plus and DRcaps® capsules) were tested as single capsules; furthermore, seven DUOCAP® capsule-in-capsule combinations were tested in a 10-way crossover open-label study in six healthy volunteers. The capsules contained iron oxide and hibiscus tea powder as tracers for visualization in MRI, and two different caffeine species (natural caffeine and 13C3) to follow caffeine release and absorption as measured by salivary levels. Results showed that the timing and location of disintegration in the gastrointestinal tract can be measured and differed when using different combinations of capsule shells. Increased variability among the six subjects was observed in most of the capsule combinations. The lowest variability in gastrointestinal localization of disintegration was observed for the DUOCAP® capsule-in-capsule configuration using a DRcaps® designed release capsule within a DRcaps® designed release outer capsule. In this combination, the inner DRcaps® designed release capsule always opened reliably after reaching the ileum. Thus, this combination enables targeted delivery to the distal small intestine. Among the single capsules tested, Vcaps® Plus HPMC capsules showed the fastest and most consistent disintegration.
RESUMO
The German Baltic Sea coastline is characterized by sea-land transitions zones, specifically coastal peatlands. Such transition zones exhibit highly fluctuating environmental parameters and dynamic gradients that affect physiological processes of inhabiting organisms such as microphytobenthic communities. In the present study four representative and abundant benthic diatom strains [Melosira nummuloides, Nitzschia filiformis, Planothidium sp. (st. 1) and Planothidium sp. (st.2)] were isolated from a Baltic Sea beach and three peatlands that are irregularly affected by Baltic Sea water intrusion. Ecophysiological and cell biological traits of the strains were investigated for the first time as function of light, temperature and salinity. The four strains exhibited euryhaline growth over a range of 1-39 SA, surpassing in situ salinity of the respective brackish habitats. Furthermore, they showed eurythermal growth over a temperature range from 5 to 30°C with an optimum temperature between 15 and 20°C. Growth rates did not exhibit any differences between the peatland and Baltic Sea strains. The photosynthetic temperature optimum of the peatland diatom isolates, however, was much higher (20-35°C) compared to the Baltic Sea one (10°C). All strains exhibited light saturation points ranging between 29.8 and 72.6 µmol photons m-2 s-1. The lipid content did not change in response to the tested abiotic factors. All data point to wide physiological tolerances in these benthic diatoms along the respective sea-land transitions zones. This study could serve as a baseline for future studies on microphytobenthic communities and their key functions, like primary production, under fluctuating environmental stressors along terrestrial-marine gradients.