Harnessing formulation and clinical pharmacology knowledge for efficient pediatric drug development: Overview and discussions from M-CERSI pediatric formulation workshop 2019.

A pediatric formulation workshop entitled "Pediatric Formulations: Challenges of Today and Strategies for Tomorrow" was held to advance pediatric drug product development efforts in both pre-competitive and competitive environments. The workshop had four main sessions discussing key considerations of Formulation, Analytical, Clinical and Regulatory. This paper focuses on the clinical session of the workshop.

A novel unit-dose approach for the pharmaceutical compounding of an orodispersible film.

Orodispersible films (ODF) have clinical potential as extemporaneous pharmacy preparations for individualized pharmacotherapy. However, the conventional method of ODF preparation using a film applicator may limit its application, due to content uniformity challenges arising from viscosity changes of the casting solution and varied operator manipulation. This study proposes the unit-dose (UD) plate as an alternative to the film applicator for compounding individual ODFs.

Application of miniaturized near-infrared spectroscopy for quality control of extemporaneous orodispersible films.

Extemporaneous oral preparations are routinely compounded in the pharmacy due to a lack of suitable formulations for special populations. Such small-scale pharmacy preparations also present an avenue for individualized pharmacotherapy. Orodispersible films (ODF) have increasingly been evaluated as a suitable dosage form for extemporaneous oral preparations.

Assessment of swallowability and palatability of oral dosage forms in children: Report from an M-CERSI pediatric formulation workshop.

The acceptability of pediatric pharmaceutical products to patients and their caregivers can have a profound impact on the resulting therapeutic outcome. However, existing methodology and approaches used for acceptability assessments for pediatric products is fragmented, making robust and consistent product evaluations difficult. A pediatric formulation development workshop took place in Washington, DC in June 2016 through the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI).

A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test.

Effect of type and ratio of solubilising polymer on characteristics of hot-melt extruded orodispersible films.

In formulating an orodispersible film (ODF), it is important for polymer choice to strike a balance between mechanical properties and release rates. Studies have been done to study polymer combinations. However, there is a lack of a systematic study to determine key factors affecting these properties.

Integrating sensitive quantification of hepatic metabolic functions by capillary electrophoresis with laser-induced fluorescence detection.

We report the establishment of capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection as a common analytical platform for sensitive quantification of both phase I and II metabolism in various hepatic in vitro models.

Novel intra-tissue perfusion system for culturing thick liver tissue.

Innovative scaffold fabrication, angiogenesis promotion, and dynamic tissue culture techniques have been utilized to improve delivery of media into the core of large tissue constructs in tissue engineering. We have developed here an intra-tissue perfusion (ITP) system, which incorporates an array of seven micron-sized needles as a delivery conduit, to improve mass transfer into the core of thick liver tissues slices (>>300 microm mass transport limit). The ITP system improves the uniformity and distribution of media throughout the tissue, resulting in improved cell viability over the static-cultured controls.

Perfusion culture improves the maintenance of cultured liver tissue slices.

Cultured precision-cut liver tissue slices are useful for studying the metabolism and toxicity of xenobiotics in liver. They may also be used to investigate the behavior of and interaction between different cell types in an intact histo-architecture. Because cultured liver tissues undergo a loss of function and morphology because of their separation from the blood supply, we investigated changes in key protein marker expressions in parenchymal and non-parenchymal cells, as well as in the extracellular matrix (ECM) at different time points.

A novel 3D mammalian cell perfusion-culture system in microfluidic channels.

Mammalian cells cultured on 2D surfaces in microfluidic channels are increasingly used in drug development and biological research applications. These systems would have more biological or clinical relevance if the cells exhibit 3D phenotypes similar to the cells in vivo. We have developed a microfluidic channel based system that allows cells to be perfusion-cultured in 3D by supporting them with adequate 3D cell-cell and cell-matrix interactions.

A configurable three-dimensional microenvironment in a microfluidic channel for primary hepatocyte culture.

We have developed a technique for the in situ three-dimensional (3D) immobilization of primary rat hepatocytes within a localized matrix in a microfluidic channel that provides a 3D microenvironment incorporating both a configurable 3D matrix and fluid perfusion. This is based on the laminar flow complex coacervation of a pair of oppositely charged polyelectrolytes, i.e.