Production and characterization of carbamazepine nanocrystals by electrospraying for continuous pharmaceutical manufacturing

In this paper, an electrospray technique followed by annealing at high temperatures was developed to produce nanocrystals of carbamazepine (CBZ), a poorly water-soluble drug, for continuous pharmaceutical manufacturing process. Electrospraying solutions of CBZ in methanol obeys the expected scaling law of current, which is I ∼ Q[superscript 1/2] (I, electrical current; Q, flow rate), for liquids with sufficiently high conductivity and viscosity. Lower flow rates during electrospraying were preferred to produce smaller diameters of monodisperse, dense CBZ nanoparticles. CBZ nanoparticles were predominantly amorphous immediately after electrospraying. Crystallization of CBZ nanoparticles was accelerated by annealing at high temperatures. CBZ nanocrystals with the most stable polymorph, form III, were obtained by annealing at 90°C, which is above the transition temperature, 78°C, for the enantiotropic CBZ form III and form I. The solubility and dissolution rates of CBZ nanocrystals increased significantly as compared with those of CBZ bulk particles. Therefore, electrospray technology has the potential to produce pharmaceutical dosage forms with enhanced bioavailability and can readily be integrated in a continuous pharmaceutical manufacturing process.Novartis-MIT Center for Continuous Manufacturin

T1 mapping in patients with cervical spinal canal stenosis with and without decompressive surgery: A longitudinal study

Background and Purpose:Cervical spinal canal stenosis (cSCS) is a common cause of spinal impairment in the elderly. With conventional magnetic resonance imaging (MRI) suffering from various limitations, high-resolution single-shot T1 mapping has been proposed as a novel MRI technique in cSCS diagnosis. In this study, we investigated the effect of conservative and surgical treatment on spinal cord T1 relaxation times in cSCS.Methods:T1-mapping was performed in 54 patients with cSCS at 3 Tesla MRI at the maximum-, above and below the stenosis. Subsequently, intraindividual T1-differences (ΔT1) intrastenosis were calculated. Twenty-four patients received follow-up scans after 6 months.Results:Surgically treated patients showed higher ΔT1 at baseline (154.9 ± 81.6 vs. 95.3 ± 60.7), while absolute T1-values within the stenosis were comparable between groups (863.7 ± 89.3 milliseconds vs. 855.1 ± 62.2 milliseconds). In surgically treated patients, ΔT1 decreased inverse to stenosis severity. After 6 months, ΔT1 significantly decreased in the surgical group (154.9 ± 81.6 milliseconds to 85.7 ± 108.9 milliseconds, p = .021) and remained unchanged in conservatively treated patients. Both groups showed clinical improvement at the 6-month follow-up.Conclusions:Baseline difference of T1 relaxation time (ΔT1) might serve as a supporting marker for treatment decision and change of T1 relaxation time might reflect relief of spinal cord narrowing indicating regenerative processes. Quantitative T1-mapping represents a promising additional imaging method to indicate a surgical treatment plan and to validate treatment success.<br

Single-Layer WEBs: Intrasaccular Flow Disrupters for Aneurysm Treatment-Feasibility Results from a European Study

ABSTRACT BACKGROUND AND PURPOSE: The safety and efficiency of the dual-layer Woven EndoBridge (WEB) device has already been published. However, this international multicenter study sought to evaluate the safety of single-layer devices, which are the newest generation of the WEB intrasaccular flow-disrupter family. They have been designed to offer smaller-sized devices with a lower profile to optimize navigability and delivery, which may, in turn, broaden their range of use

Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry

Introduction Endovascular treatment (EVT) for tandem occlusion (TO) of the anterior circulation is complex but effective. The effect of extracranial internal carotid artery (EICA) lesion severity on the outcomes of EVT is unknown. In this study we investigated the effect of EICA lesion severity on the outcomes of tandem occlusion EVT. Methods A multicenter retrospective TITAN (Thrombectomy In TANdem lesions) study that included 18 international endovascular capable centers was performed. Patients who received EVT for atherosclerotic TO with or without EICA lesion intervention were included. Patients were divided into two groups based on the EICA lesion severity (high-grade stenosis (>= 90% North American Symptomatic Carotid Endarterectomy Trial) vs complete occlusion). Outcome measures included the 90-day clinical outcome (modified Rankin Scale score (mRS)), angiographic reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) at the end of the procedure), procedural complications, and intracranial hemorrhage at 24 hours follow-up. Results A total of 305 patients were included in the study, of whom 135 had complete EICA occlusion and 170 had severe EICA stenosis. The EICA occlusion group had shorter mean onset-to-groin time (259 +/- 120 min vs 305 +/- 202 min;p=0.037), more patients with diabetes, and fewer with hyperlipidemia. With respect to the outcome, mTICI 2b-3 reperfusion was lower in the EICA occlusion group (70% vs 81%;p=0.03). The favorable outcome (90-day mRS 0-2), intracerebral hemorrhage and procedural complications were similar in both groups. Conclusion Atherosclerotic occlusion of the EICA in acute tandem strokes was associated with a lower rate of mTICI 2b-3 reperfusion but similar functional and safety outcomes when compared with high-grade EICA stenosis

Thermoanalytical studies of carbamazepine: hydration/dehydration, thermal decomposition, and solid phase transitions

Carbamazepine (CBZ), a widely used anticonvulsant drug, can crystallize and exhibits four polymorphic forms and one dihydrate. Anhydrous CBZ can spontaneously absorb water and convert to the hydrate form whose different crystallinity leads to lower biological activity. The present study was concerned to the possibility of recovering the hydrated form by heating. The thermal behavior of spontaneously hydrated carbamazepine was investigated by TG/DTG-DTA and DSC in dynamic atmospheres of air and nitrogen, which revealed that the spontaneous hydration of this pharmaceutical resulted in a Form III hydrate with 1.5 water molecules. After dehydration, this anhydrous Form III converted to Form I, which melted and decomposed in a single event, releasing isocyanic acid, as shown by evolved gas analysis using TG-FTIR. Differential scanning calorimetry analyses revealed that Form III melted and crystallized as Form I, and that subsequent cooling cycles only generated Form I by crystallization. Solid state decomposition kinetic studies showed that there was no change in the substance after the elimination of water by heating to 120 °C. Activation energies of 98 ± 2 and 93 ± 2 kJ mol-1 were found for the hydrated and dried samples, respectively, and similar profiles of activation energy as a function of conversion factor were observed for these samples

The Quantum Mind: Alternative Ways of Reasoning with Uncertainty

© 2018, Ontario Institute for Educational Studies (OISE). Human reasoning about and with uncertainty is often at odds with the principles of classical probability. Order effects, conjunction biases, and sure-thing inclinations suggest that an entirely different set of probability axioms could be developed and indeed may be needed to describe such habits. Recent work in diverse fields, including cognitive science, economics, and information theory, explores alternative approaches to decision theory. This work considers more expansive theories of reasoning with uncertainty while continuing to recognize the value of classical probability. In this paper, we discuss one such alternative approach, called quantum probability, and explore its applications within decision theory. Quantum probability is designed to formalize uncertainty as an ontological feature of the state of affairs, offering a mathematical model for entanglement, de/coherence, and interference, which are all concepts with unique onto-epistemological relevance for social theorists working in new and trans-materialisms. In this paper, we suggest that this work be considered part of the quantum turn in the social sciences and humanities. Our aim is to explore different models and formalizations of decision theory that attend to the situatedness of judgment. We suggest that the alternative models of reasoning explored in this article might be better suited to queries about entangled mathematical concepts and, thus, be helpful in rethinking both curriculum and learning theory

Latent autoimmune diabetes in adults (LADA) should be less latent

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