Critical review on the role of excipient properties in pharmaceutical powder-to-tablet continuous manufacturing.

Introduction: The pharmaceutical industry is gradually changing batch-wise manufacturing processes to continuous manufacturing processes, due to the advantages it has to offer. The final product quality and process efficiency of continuous manufacturing processes is among others impacted by the properties of the raw materials. Existing knowledge on the role of raw material properties in batch processing is however not directly transferable to continuous processes, due to the inherent differences between batch and continuous processes.

Compartmentalized role of xCT in supporting pancreatic tumor growth, inflammation and mood disturbance in mice.

xCT (Slc7a11), the specific subunit of the cystine/glutamate antiporter system x, is present in the brain and on immune cells, where it is known to modulate behavior and inflammatory responses. In a variety of cancers -including pancreatic ductal adenocarcinoma (PDAC)-, xCT is upregulated by tumor cells to support their growth and spread. Therefore, we studied the impact of xCT deletion in pancreatic tumor cells (Panc02) and/or the host (xCT mice) on tumor burden, inflammation, cachexia and mood disturbances.

Lubricant Sensitivity of Direct Compression Grades of Lactose in Continuous and Batch Tableting Process.

Modern pharmaceutical manufacturing based on Quality by Design and digitalisation is revolutionising the pharmaceutical industry. Continuous processes are promoted as they increase efficiency and improve quality control. Compared to batch blending, continuous blending is easier to scale and provides advantages for achieving blend homogeneity.

Complexities related to the amorphous content of lactose carriers.

Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task.

Pancreatic acinar cell fate relies on system x to prevent ferroptosis during stress.

Acinar cell dedifferentiation is one of the most notable features of acute and chronic pancreatitis. It can also be the initial step that facilitates pancreatic cancer development. In the present study, we further decipher the precise mechanisms and regulation using primary human cells and murine experimental models.

Smart Specification Setting for Dry Powder Inhalation Carriers.

The specifications of excipients are important to pharmaceutical manufacturers to ensure that the final product can be manufactured robustly over the entire lifecycle of a drug product. Particle size specifications are key for dry powder inhalation excipients and they should be agreed between users and suppliers. The current paper evaluates two development strategies to set particle size specifications.

The impact of lactose type on disintegration: An integral study on porosity and polymorphism.

Besides factors such as disintegrant and lubricant, the raw material properties of filler excipients can have an impact on the disintegration behavior of a tablet. The current research aims to model the impact of lactose properties on disintegration time. For the first time, the impact of lactose polymorphism, tablet tensile strength, and pore structure parameters on disintegration were evaluated in one study.

Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes.

Chronic non-healing wounds are a major complication of diabetes, which affects 1 in 10 people worldwide. Dying cells in the wound perpetuate the inflammation and contribute to dysregulated tissue repair. Here we reveal that the membrane transporter SLC7A11 acts as a molecular brake on efferocytosis, the process by which dying cells are removed, and that inhibiting SLC7A11 function can accelerate wound healing.

The effect of excipient particle size on the reduction of compactibility after roller compaction.

Developing a robust roller compaction process can be challenging, due to the diversity in process parameters and material properties of the components in a formulation. A major challenge in dry granulation is the reduction of tablet strength as a result of re-compaction of the materials. The aim of this study is to investigate the impact of excipient type and particle size distribution on tablet tensile strength after roller compaction.

Lifespan extension with preservation of hippocampal function in aged system x-deficient male mice.

The cystine/glutamate antiporter system x has been identified as the major source of extracellular glutamate in several brain regions as well as a modulator of neuroinflammation, and genetic deletion of its specific subunit xCT (xCT) is protective in mouse models for age-related neurological disorders. However, the previously observed oxidative shift in the plasma cystine/cysteine ratio of adult xCT mice led to the hypothesis that system x deletion would negatively affect life- and healthspan. Still, till now the role of system x in physiological aging remains unexplored.

Batch versus continuous blending of binary and ternary pharmaceutical powder mixtures.

The material properties of excipients and active pharmaceutical ingredients (API's) are important parameters that affect blend uniformity of pharmaceutical powder formulations. With the current shift from batch to continuous manufacturing in the pharmaceutical industry, blending of excipients and API is converted to a continuous process. The relation between material properties and blend homogeneity, however, is generally based on batch-wise blending trials.

Impact of Powder Properties on the Rheological Behavior of Excipients.

With the emergence of quality by design in the pharmaceutical industry, it becomes imperative to gain a deeper mechanistic understanding of factors impacting the flow of a formulation into tableting dies. Many flow characterization techniques are present, but so far only a few have shown to mimic the die filling process successfully. One of the challenges in mimicking the die filling process is the impact of rheological powder behavior as a result of differences in flow field in the feeding frame.

Cystine-glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice.

xCT is the specific subunit of System xc-, an antiporter importing cystine while releasing glutamate. Although xCT expression has been found in the spinal cord, its expression and role after spinal cord injury (SCI) remain unknown. The aim of this study was to characterize the role of xCT on functional and histological outcomes following SCI induced in wild-type (xCT+/+) and in xCT-deficient mice (xCT-/-).

Chronic Sulfasalazine Treatment in Mice Induces System x - Independent Adverse Effects.

Despite ample evidence for the therapeutic potential of inhibition of the cystine/glutamate antiporter system x in neurological disorders and in cancer, none of the proposed inhibitors is selective. In this context, a lot of research has been performed using the EMA- and FDA-approved drug sulfasalazine (SAS). Even though this molecule is already on the market for decades as an anti-inflammatory drug, serious side effects due to its use have been reported.

Corticostriatal dysfunction and social interaction deficits in mice lacking the cystine/glutamate antiporter.

The astrocytic cystine/glutamate antiporter system x represents an important source of extracellular glutamate in the central nervous system, with potential impact on excitatory neurotransmission. Yet, its function and importance in brain physiology remain incompletely understood. Employing slice electrophysiology and mice with a genetic deletion of the specific subunit of system x, xCT (xCT mice), we uncovered decreased neurotransmission at corticostriatal synapses.