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Eindhoven, Netherlands

Kostewicz E.S.,Goethe University Frankfurt | Abrahamsson B.,Astrazeneca | Brewster M.,Drug Product Development | Brouwers J.,Catholic University of Leuven | And 15 more authors.
European Journal of Pharmaceutical Sciences

Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been ignored. More recently, the switch to assessing drug products in a more biorelevant and mechanistic manner has advanced the understanding of drug formulation behavior. Notwithstanding this evolution, predicting the in vivo biopharmaceutical performance of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation...) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro tools. Development and optimizing innovative, predictive Oral Biopharmaceutical Tools is the main target of the OrBiTo project within the Innovative Medicines Initiative (IMI) framework. A combination of physico-chemical measurements, in vitro tests, in vivo methods, and physiology-based pharmacokinetic modeling is expected to create a unique knowledge platform, enabling the bottlenecks in drug development to be removed and the whole process of drug development to become more efficient. As part of the basis for the OrBiTo project, this review summarizes the current status of predictive in vitro assessment tools for formulation behavior. Both pharmacopoeia-listed apparatus and more advanced tools are discussed. Special attention is paid to major issues limiting the predictive power of traditional tools, including the simulation of dynamic changes in gastrointestinal conditions, the adequate reproduction of gastrointestinal motility, the simulation of supersaturation and precipitation, and the implementation of the solubility-permeability interplay. It is anticipated that the innovative in vitro biopharmaceutical tools arising from the OrBiTo project will lead to improved predictions for in vivo behavior of drug formulations in the GI tract. © 2013 Elsevier B.V. All rights reserved. Source

Development Laboratories | Date: 1994-05-31

printed test forms consisting of psychological tests and assessment measures; test manuals; books related to tests and assessment devices.

Lalloo A.K.,Merck And Co. | McConnell E.L.,Development Laboratories | Jin L.,Merck And Co. | Elkes R.,Development Laboratories | And 2 more authors.
International Journal of Pharmaceutics

Gastric retention is postulated as an approach to improve bioavailability of compounds with narrow absorption windows. To elucidate the role of image size on gastric retention and pharmacokinetics, formulations with different image sizes and swelling kinetics but similar dissolution rates were designed and imaged in dogs. Diet had a clear effect, with increasing calorific intake prolonging retention in the dog model. In contrast to clinical observations, no obvious effect of image size on gastric retention was observed in the dog, with the larger gastric retentive (GR) and smaller controlled release (CR) formulations both demonstrating similar gastric emptying. Comparable pharmacokinetic profiles were observed for the two formulations, corroborating the imaging data and providing evidence of similar in vivo dissolution rates and dosage form integrity in the dog. Food, specifically meal composition, resulted in comparable enhancements in exposure in the dog and clinic due to prolonged gastric retention. However, differentiating retention based on image size in the dog was not feasible due to the smaller pyloric aperture compared to humans. This work illustrates that the dog is capable of determining the pharmacokinetic advantage of gastric retention relative to immediate release (IR) or CR formulations, however, has limited value in differentiating between CR and GR formulations. © 2012 Elsevier B.V. All rights reserved. Source

Peters H.J.,Technical University of Delft | Peters H.J.,Development Laboratories | Goosen J.F.L.,Technical University of Delft | Van Keulen F.,Technical University of Delft
International Journal of Micro Air Vehicles

Energy-effective hovering and active flight control are of paramount importance for the usefulness of Flapping Wing Micro Air Vehicles (FWMAVs). Recent studies have focused on separate parts (e.g., wing planform design, wing kinematics, or flight control) rather than on the complete system. This work presents a combined approach to find an optimal wing design (i.e., wing planform and pitching kinematics) for energy-effective hovering and roll control. Relatively simple mathematical descriptions are used for the kinematics, the aerodynamics and the roll motion to allow its use in optimization techniques. Results show that the wing design depends significantly on the relative importance of either energy-effective hovering or effective roll control during the optimization. The roll control effectiveness increases if the wing area around the wingtip is increased to push the center of lift outwards. Additionally, we show that the most effective control variable, to enforce the required body moment for the roll motion, depends strongly on the wing design. In conclusion, flapping wing design requires, in general, a combined approach to guarantee both energy-effective hovering and effective roll control. © 2015, Multi-Science Publishing Co. Ltd. All rights reserved. Source

Peters H.J.,Technical University of Delft | Peters H.J.,Development Laboratories | Goosen J.F.L.,Technical University of Delft | Keulen F.V.,Technical University of Delft
Smart Materials and Structures

Lightweight vibrating structures (such as flapping wing micro air vehicle (FWMAV) designs) often require some form of control. To achieve controllability, local structural property changes (e.g., damping and stiffness changes) might be induced in an active manner. The stroke-averaged lift force production of a FWMAV wing can be modified by changing the structural properties of that wing at carefully selected places (e.g., changing the properties of the elastic hinge at the wing root as studied in this work). To actively change the structural properties, we investigate three different methods which are based on: (1) piezoelectric polymers, (2) electrorheological fluids, and (3) electrostatic softening. This work aims to gain simple yet insightful ways to determine the potential of these methods without focusing on the precise modeling. Analytical models of FWMAV wing designs that include control approaches based on these three methods are used to calculate the achievable lift force modifications after activating these methods. The lift force production as a result of a wing flapping motion is determined using a quasi-steady aerodynamic model. Both piezoelectric polymers and electrostatic softening are found to be promising in changing the structural properties and, hence, the lift force production of FWMAV wings. For the control of lightweight FWMAV designs, numerical simulations reveal a promising roll maneuverability due to the induced lift force difference between a pair of opposite wings. Although applied to a specific FWMAV design, this work is relevant for control of small, lightweight, possible compliant, vibrating structures in general. © 2016 IOP Publishing Ltd. Source

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