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Pregnant women with low blood folate levels have an increased risk of a miscarriage, according to a study of 468 pregnant women who had a miscarriage and 921 pregnant women who did not. Folate is a naturally occurring substance in the body that has also been linked to birth defects in women with a folate deficiency.

Aim: The aim of this study was to maximize the exposure of a model compound (MC) for forthcoming high-dose toxicological studies with the physical form of the original compound unaffected. Method: The two evaluated formulation approaches for the present poorly water-soluble compound were micro- and nanosuspensions. Results: The particle size was about 280 nm for the nanosuspensions and about 4 μm for the microsuspensions. The crystallinity and the crystalline form of the ground samples were conserved. The physical and the chemical stabilities of the two kinds of suspensions were unaffected during the investigated time period. The in vivo results of the study showed that the pharmacokinetic parameters investigated were comparable at the low-dose level (6 μmol/kg) for both formulations after single administration. However, at the two higher doses (60 and 300 μmol/kg), a significant difference in exposure was observed between the two suspensions with an improved exposure for smaller particles. After Day 7 of repeated administration, a significant difference in exposure was observed at all dose levels. The overall exposures were higher on Day 7, compared to the exposures on Day 1 (most significant for nanoparticles), due to an accumulation of compound in the body. Conclusions: The nanoparticles have a larger surface, resulting in faster in vivo dissolution rate, faster absorption, and increased bioavailability, compared to microparticles. The differences in systemic exposure of model compound, following oral administration of nano- or microparticles of the drug substance, are probably caused by differences in the in vivo dissolution rate and possibly further enhanced by saturation of the systemic elimination. [ABSTRACT FROM AUTHOR]

During the last 10 years the European Medicines Agency (EMA) organized a number of workshops on modeling and simulation, working towards greater integration of modeling and simulation (M&S) in the development and regulatory assessment of medicines. In the 2011 EMA - European Federation of Pharmaceutical Industries and Associations (EFPIA) Workshop on Modelling and Simulation, European regulators agreed to the necessity to build expertise to be able to review M&S data provided by companies in their dossier. This led to the establishment of the EMA Modelling and Simulation Working Group (MSWG). Also, there was agreement reached on the need for harmonization on good M&S practices and for continuing dialog across all parties. The MSWG acknowledges the initiative of the EFPIA Model-Informed Drug Discovery and Development (MID3) group in promoting greater consistency in practice, application, and documentation of M&S and considers the paper is an important contribution towards achieving this objective. [ABSTRACT FROM AUTHOR]