Flow Equations for Free-Flowable Particle Fractions of Sorbitol for Direct Compression: An Exploratory Multiple Regression Analysis of Particle and Orifice Size Influence.

Flowability is among the most important properties of powders, especially when fine particle size fractions need to be processed. In this study, our goal was to find a possibly simple but accurate mathematical model for predicting the mass flow rate for different fractions of the pharmaceutical excipient sorbitol for direct compression. Various regression models derived from the Jones-Pilpel equation for the prediction of the mass flow rate were investigated. Using validation with experimental data for various particle and hopper orifice sizes, we focused on the prediction accuracy of the respective models, i.e., on the relative difference between measured and model-predicted values. Classical indicators of regression quality from statistics were addressed as well, but we consider high prediction accuracy to be particularly important for industrial processing in practice. For individual particle size fractions, the best results (an average prediction accuracy of 3.8%) were obtained using simple regression on orifice size. However, for higher accuracy (3.1%) in a unifying model, valid in the broad particle size range 0.100-0.346 mm, a fully quadratic model, incorporating interaction between particle and orifice size, appears to be most appropriate.

The importance of the coating material type and amount in the preparation of liquisolid systems based on magnesium aluminometasilicate carrier.

Albeit the preparation of liquisolid systems represents an innovative approach to enhance the dissolution of poorly soluble drugs, their broader utilization is still limited mainly due to the problematic conversion of the liquid into freely flowing and readily compressible powder. Accordingly, the presented study aims to determine the optimal carrier/coating material ratio (R value) for formulations based on magnesium aluminometasilicate (NUS2) loaded with polyethylene glycol 400. Four commercially available colloidal silica were used as coating materials in nine different R values (range of 5 - 100). The obtained results suggested that the higher R value leads to the superior properties of powder mixtures, such as better flowability, as well as compacts with higher tensile strength and lower friability. Moreover, it was observed that the type of coating material impacts the properties of liquisolid systems due to the different arrangement of particles in the liquisolid mixture. To confirm the noted dependency of R value and coating material type, the one- and two-way ANOVA, linear regression and principal component analysis (PCA) techniques were performed. In addition, a comparison of results with the properties of loaded NUS2 itself revealed that LSS with sufficient properties may be prepared even without the coating material.

Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth.

Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory markers (such as maternal serum C-reactive protein and white blood cell count). We show that preterm birth is associated with significant changes in placental tryptophan metabolism. Multifactorial analysis revealed similarities in expression patterns associated with multiple phenotypes of preterm delivery. Subsequent correlation computations and mediation analyses identified links between intra-amniotic and maternal inflammatory markers and placental serotonin and kynurenine pathways of tryptophan catabolism. Collectively, the findings suggest that a hostile inflammatory environment associated with preterm delivery underlies the mechanisms affecting placental endocrine/transport functions and may contribute to disruption of developmental programming of the fetal brain.