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Introduction: Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management. Objectives: Using metabolomic analysis we investigated the prenatal prediction of maternal and newborn complications in early and late PreE and investigated the pathogenesis of such complications. Methods: Serum samples from 76 cases of PreE (36 early-onset and 40 late-onset), and 40 unaffected controls were collected. Direct Injection Liquid Chromatography–Mass Spectrometry combined with Nuclear Magnetic Resonance (NMR) spectroscopy was performed. Logistic regression analysis was used to generate models for prediction of adverse maternal and neonatal outcomes in patients with PreE. Metabolite set enrichment analysis (MSEA) was used to identify the most dysregulated metabolites and pathways in PreE. Results: Forty-three metabolites were significantly altered (p < 0.05) in PreE cases with maternal complications and 162 metabolites were altered in PreE cases with newborn adverse outcomes. The top metabolite prediction model achieved an area under the receiver operating characteristic curve (AUC) = 0.806 (0.660–0.952) for predicting adverse maternal outcomes in early-onset PreE, while the AUC for late-onset PreE was 0.843 (0.712–0.974). For the prediction of adverse newborn outcomes, regression models achieved an AUC = 0.828 (0.674–0.982) in early-onset PreE and 0.911 (0.828–0.994) in late-onset PreE. Profound alterations of lipid metabolism were associated with adverse outcomes. Conclusion: Prenatal metabolomic markers achieved robust prediction, superior to conventional markers for the prediction of adverse maternal and newborn outcomes in patients with PreE. We report for the first-time the prediction and metabolomic basis of adverse maternal and newborn outcomes in patients with PreE. [ABSTRACT FROM AUTHOR]

The acceptability and palatability of a dosage form are extremely important to improve patient compliance. Mixing oral solid dosage forms with food carriers is often necessary to ease swallowing and provide the taste-masking effect. The present research investigated how a liquid or semisolid carrier influences the disintegration time and drug dissolution rate of pellets and minitablets with diazepam. The disintegration of pellets and minitablets in liquid carriers (water, milk and apple juice) was determined using a texture analyser. Dissolution tests were performed for the dosage forms dispersed in gel vehicles (2% carmellose and 0.5% carbomer gels) or applesauce. The disintegration of minitablets in water and apple juice was fast (1 min), but it slowed to 3 and 5 min in milk and gel vehicles, respectively. The pellets disintegrated in liquid carriers within 3 min. The drug dissolution rate in 0.1 M HCl depended on the gel viscosity in this medium. The preserved high viscosity of a carmellose gel inhibited the dissolution of diazepam. On the other hand, the viscosity of the carbomer gel decreased rapidly, and in effect, the dissolution rate of diazepam from the incorporated pellets or minitablets was comparable to the dissolution from loose pellets or minitablets. [ABSTRACT FROM AUTHOR]