The goal of the present work was to develop an in vitro toolbox to evaluate the oral administration of dosage forms to children of different age groups and under different administration conditions (fasted/fed). Based on current data on the gastrointestinal physiology of children, a set of new biorelevant media was designed to mimic the composition and physicochemical properties of resting gastric and resting small intestinal fluid in children of different age groups. In addition, guidelines were developed on how to generate fasted and fed state gastric and small intestinal fluids by combining these media with age-specific drinking volumes or portions of already established simulated paediatric breakfast meals, respectively.
View Article and Find Full Text PDFSelecting the appropriate formulation and solubility-enabling technology for poorly water soluble drugs is an essential element in the development of formulations for paediatric patients. Different methodologies and structured strategies are available to select a suitable approach and guide formulation scientists for development of adult formulations. However, there is paucity of available literature for selection of technology and overcoming the challenges in paediatric formulation development.
View Article and Find Full Text PDFSince co-administration of dosage forms with food can impact drug exposure, food effect studies became an integral part of oral drug product development. Studies are usually performed in healthy adults and the dosage form is co-administered with a high-fat high-calorie standard breakfast meal to mimic worst-case dosing conditions. A corresponding study design for children is lacking but would be essential for a proper risk-assessment in this vulnerable patient group.
View Article and Find Full Text PDFFundamental knowledge about the composition of intestinal fluids in paediatric populations is currently unavailable. This study aimed to characterise gastric and intestinal fluid from paediatric populations. Gastric and intestinal fluid samples were obtained during routine clinical endoscopy from paediatric patients at a large teaching hospital.
View Article and Find Full Text PDFWe hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG₇₅₀-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.
View Article and Find Full Text PDFThis work investigates the flocculation effect of polyethylene glycol (PEG) on typical aqueous dispersions, such as O/W emulsions and solid/liquid suspensions. Hereby, sunflower oil and flubendazole were selected as model ingredients, whereas microfluidization at variable driving air pressure was used to enable particle size distribution variations for both systems. The molecular weight of PEG varied from 2000 to 12,000g/mol while its concentration ranged from 50 to 100mg/ml.
View Article and Find Full Text PDFThis work aims to demonstrate the usefulness of a low-field one-dimensional pulsed-field gradient NMR (1D pfg NMR) profilometry technique to enable in situ nondestructive sediment characterization and resuspendability quantification of concentrated prefilled injectable suspensions. Aqueous paliperidone palmitate suspensions were used as model samples and low-intensity centrifugation was evaluated as a long-term gravity simulation approach. The low-field 1D pfg NMR technique allowed a detection zone of 2.
View Article and Find Full Text PDFIn order to study the sedimentation of pharmaceutical suspensions using low-field one dimensional pulsed field gradient nuclear magnetic resonance (1D pfg NMR) profilometry, the accuracy of signal acquisition as well as the spatial resolution of a commercial spectrometer operating at 23.4 MHz was investigated. The use of a solid Teflon spacer revealed that the accuracy of signal acquisition was independent of spatial position (height).
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