Continuous direct compression as manufacturing platform for sustained release tablets

This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard Methocel CR and directly compressible Methocel DC2. The feeding behavior of each formulation component was investigated by deriving feed factor profiles. The maximum feed factor was used to estimate the drive command and depended strongly upon the density of the material. Furthermore, the shape of the feed factor profile allowed definition of a customized refill regime for each material. Inline NIRs was used to estimate the residence time distribution (RTD) in the mixer and monitor blend uniformity. Tablet content and weight variability were determined as additional measures of mixing performance. For Methocel CR, the best axial mixing (i.e. feeder fluctuation dampening) was achieved when an impeller with high number of radial mixing blades operated at low speed. However, the variability in tablet weight and content uniformity deteriorated under this condition. One can therefore conclude that balancing axial mixing with tablet quality is critical for Methocel CR. However, reformulating with the direct compressible Methocel DC2 as matrix former improved tablet quality vastly. Furthermore, both process and product were significantly more robust to changes in process and design variables. This observation underpins the importance of flowability during continuous blending and die-filling. At the compaction stage, blends with Methocel CR showed better tabletability driven by a higher compressibility as the smaller CR particles have a higher bonding area. However, tablets of similar strength were achieved using Methocel DC2 by targeting equal porosity. Compaction pressure impacted tablet properties and dissolution. Hence controlling thickness during continuous manufacturing of sustained release tablets was crucial to ensure reproducible dissolution. (C) 2017 Elsevier B.V. All rights reserved

Long axial field of view PET/CT in critically ill patients:lessons from a case report

The introduction of new long axial field of view (LAFOV) scanners is a major milestone in positron emission tomography/computed tomography (PET/CT) imaging. With these new systems a revolutionary reduction in scan time can be achieved, concurrently lowering tracer dose. Therefore, PET/CT has come within reach for groups of patients in whom PET/CT previously was undesirable. In this case report we discuss the procedure of a continuous bed motion (CBM) total-body [18F]FDG PET/CT scan in an intensive care patient. We emphasize the clinical and technical possibilities with this new camera system, a matched clinical protocol, and the added value of a dedicated team.</p

Improved [¹⁸F]FDG PET/CT Diagnostic Accuracy for Infective Endocarditis Using Conventional Cardiac Gating or Combined Cardiac and Respiratory Motion Correction (CardioFreeze^TM)

Infective endocarditis (IE) is a serious and diagnostically challenging condition. [18F]FDG PET/CT is valuable for evaluating suspected IE, but it is susceptible to motion-related artefacts. This study investigated the potential benefits of cardiac motion correction for [18F]FDG PET/CT. In this prospective study, patients underwent [18F]FDG PET/CT for suspected IE, combined with a conventional cardiac gating sequence, a data-driven cardiac and respiratory gating sequence (CardioFreezeTM), or both. Scans were performed in adherence to EANM guidelines and assessors were blinded to patients’ clinical contexts. Final diagnosis of IE was established based on multidisciplinary consensus after a minimum of 4 months follow-up and surgical findings, whenever performed. Seven patients participated in the study, undergoing both an ungated [18F] FDG-PET/CT and a scan with either conventional cardiac gating, CardioFreezeTM, or both. Cardiac motion correction improved the interpretability of [18F]FDG PET/CT in four out of five patients with valvular IE lesions, regardless of the method of motion correction used, which was statistically significant by Wilcoxon’s signed rank test: p = 0.046. In one patient the motion-corrected sequence confirmed the diagnosis of endocarditis, which had been missed on non-gated PET. The performance of the two gating sequences was comparable. In conclusion, in this exploratory study, cardiac motion correction of [18F]FDG PET/CT improved the interpretability of [18F]FDG PET/CT. This may improve the sensitivity of PET/CT for suspected IE. Further larger comparative studies are necessary to confirm the additive value of these cardiac motion correction methods.</p

Virally induced modulation of murine IgG antibody subclasses.

The isotypic distribution of murine IgG was examined after infection with several viruses. The results indicate that when a hypergammaglobulinemia was induced by the infection, it was restricted to the IgG2a and, to a lesser extent, to the IgG2b subclasses. In addition, when mice were infected with some viruses concomitantly with the immunization with a soluble protein antigen, a modification in the isotypic distribution of antiprotein antibodies was observed, with a preferential production of IgG2a. These observations indicate that viral infections can actively influence the switch of Igs and selectively stimulate the production of the IgG2a subclass