European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
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Compounding of cytostatic drugs requires strict aseptic procedures, while exposure to toxic drugs and repetitive manual movements should be minimized. Furthermore, reuse of vials is desirable to lower the costs. To assess if all this might be safely achieved with a robot, this study aimed at qualifying the aseptic preparation process with the robotic system APOTECAchemo. ⋯ Robotical compounding of cytostatic drugs with APOTECAchemo meets the microbiological requirements of the European GMP. In addition, the robot can reuse vials repeatedly and safely, thereby enabling extended usage.
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For about 15 years the performance of dry powder inhalers (DPIs) has been numerically analysed through CFD (computational fluid dynamics) approaches with the objective of understanding the evolving flow structures and the resulting transport of drug particles. Naturally the main interest is the numerical prediction of the emitted fine particle fraction (FPF) which is able to penetrate the lung airways. Due to the mostly used drug formulations (i.e. carrier-based or agglomerated drug powder) and the complex elementary processes occurring during the transport of such particles through inhalers this is not an easy task. ⋯ Hence, the predicted fine particle fraction was found to be close to 100% for both inhalers. As a conclusion of this study, it has become clear that the wall deposition of fine drug particles is an important mechanism during carrier or agglomerate wall collisions, which are responsible for the low emitted fine particle fraction (FPF) observed experimentally. It is hoped that this article provides requirements and guidelines for the further development of Euler/Lagrange simulations applied to dry powder inhaler devices.
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Randomized Controlled Trial
Pharmacokinetic and pharmaceutical properties of a novel buprenorphine/naloxone sublingual tablet for opioid substitution therapy versus conventional buprenorphine/naloxone sublingual tablet in healthy volunteers.
A novel sublingual buprenorphine/naloxone rapidly-dissolving tablet (BNX-RDT) for opioid substitution therapy has been developed for improved bioavailability, rapid disintegration and improved taste masking. We compared the bioavailability and pharmaceutical properties of BNX-RDT with conventional buprenorphine/naloxone sublingual tablets (BNX). ⋯ BNX-RDT provided improved buprenorphine absorption compared to a conventional sublingual tablet, with shorter dissolve times and improved taste and mouthfeel, resulting in a high preference for the novel formulation.
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Randomized Controlled Trial
Population pharmacokinetic evaluation of ADV6209, an innovative oral solution of midazolam containing cyclodextrin.
In the absence of a licensed formulation in many countries worldwide, ADV6209, an innovative 2mg/ml oral solution of midazolam containing cyclodextrin, has been developed for moderate sedation in paediatric patients. Population pharmacokinetics for ADV6209 is reported. ⋯ Pharmacokinetic parameters were close to those reported in the literature with midazolam extemporaneous oral solutions or syrups, demonstrating that cyclodextrin had no significant effect on measured parameters.
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Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human, and to predict drug concentration-time profiles in multiple CNS compartments on available human data of four drugs (acetaminophen, oxycodone, morphine and phenytoin). Values of the system-specific parameters in the rat CNS PBPK model were replaced by corresponding human values. ⋯ The human CNS PBPK model could successfully predict their concentration-time profiles in multiple human CNS compartments in physiological CNS conditions within a 1.6-fold error. Furthermore, the model allowed investigation of the potential underlying mechanisms that can explain differences in CNS PK associated with pathophysiological changes. This analysis supports the relevance of the developed model to allow more effective selection of CNS drug candidates since it enables the prediction of CNS target-site concentrations in humans, which are essential for drug development and patient treatment.