Effect of excipient particle size distribution variability on compact tensile strength; and its in-line prediction by force-displacement and force-time profiling.

Background: Direct compression is potentially sensitive to particle size distribution (PSD) variability in pharmaceutical grade excipients. Yet, the impact is insufficiently studied. Furthermore, the use of force sensor as a process analytical technology (PAT) platform, to monitor the effect of PSD variations on compact tensile strength, is a readily available but underutilized strategy.

De-risking excipient particle size distribution variability with automated robust mixing: Integrating quality by design and process analytical technology.

Background: Particle size distribution (PSD) variability in excipients affects mixing. In response, manufacturers rely on raw material control and rigidly defined process parameters to achieve quality. However, this status quo is costly; and diverges from regulatory exceptions for process robustness.

3D projection and multivariate image analysis for quantitative visual modelling of mixability and rheological behavior of lactose powder.

Background: This study reports the use of multivariate time and image analysis of avalanche videographic data for quantitative visual modelling of mixability. Its usefulness, in mechanistically modelling a powder's rheological behavior in relation to mixing, was evaluated.

Methods: Particle size distribution (PSD) of a pharmaceutical grade lactose powder was modified to reflect commercially encountered variability.

The effect of rotation speed and particle size distribution variability on mixability: An avalanche rheological and multivariate image analytical approach.

The utility of modulating rotation speed in tumble mixing and its mechanistic interplay with particle size distribution (PSD) variability in excipients remain underexplored. They were investigated in this study. For the present purpose, PSD of a commercial grade lactose was modified to reflect commercially relevant variations; and mixed with microcrystalline cellulose and chlorpheniramine in a double-cone blender, at various rotation speeds.

Near infrared spectroscopy for rapid and in-line detection of particle size distribution variability in lactose during mixing.

Particle size distribution (PSD) variability in excipients may cause unacceptable prolongation of mixing time needed to achieve blend homogeneity. Therefore, it is vital to modulate mixing through real-time monitoring of PSD variability. Notwithstanding the criticality of PSD variability, real-time measurement of PSD during mixing is relatively unexplored; and this is the focus of the present study.

Investigating the effect and mechanism of particle size distribution variability on mixing using avalanche testing and multivariate modelling.

Particle size distribution (PSD) variability in excipients is widely thought to affect the mixing process and the achievement of blend homogeneity. Yet, few studies have addressed this issue by attempting to ascertain the relationship and elucidate its mechanism. To address this, the model material, lactose, was modified to reflect commercially relevant PSD variations and mixed with microcrystalline cellulose and chlorpheniramine in a double-cone blender.

Clinical validation and implications of dried blood spot sampling of carbamazepine, valproic acid and phenytoin in patients with epilepsy.

To facilitate therapeutic monitoring of antiepileptic drugs (AEDs) by healthcare professionals for patients with epilepsy (PWE), we applied a GC-MS assay to measure three AEDs: carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) levels concurrently in one dried blood spot (DBS), and validated the DBS-measured levels to their plasma levels. 169 PWE on either mono- or polytherapy of CBZ, PHT or/and VPA were included. One DBS, containing ∼15 µL of blood, was acquired for the simultaneous measurement of the drug levels using GC-MS.