Bioavailability

Transepithelial transport in a cell model with analysis and upstream cell-free digestion model

The transport of an active ingredient across the small intestinal mucosa is a prerequisite for it to develop its effect in the body. In vitro tests serve as a valuable building block during product development or further refinement. The determination of an analyt’s transport rate can be carried out with or without prior simulated gastric and intestinal passage.

The model is particularly suitable for the simultaneous comparative determination of the transport rate during product development, quality assurance, accompanying product modification or in comparison to a benchmark product.

Our modular package solution:

Simulated gastro-intestinal passage:

The processes occurring during the residence time in the stomach and small intestine are simulated using enzyme addition and pH adjustments in the in vitro setup. The test substances introduced are subjected to potential metabolic processes (e.g. cleavage of sugar residues) similar to those observed in vivo. Water-insoluble active components are incorporated into micelles by the added enzymes and bile salts, making them soluble for subsequent transport studies.

Particle size determination:

The particle size is determined via dynamic light scattering (DLS) at various time points before and during the gastric and intestinal phases. This provides valuable information about the solubility and stability of the formulation.

Transepithelial transport:

Transepithelial transport is determined in the Caco-2 model (optionally also with EpiIntestinal^TM). In the model, the epithelium consisting of differentiated cells on a membrane separates the two compartments:

• The apical side, which represents the intestinal lumen containing the active ingredients
• The basal side symbolising the systemic side of the body into which the active ingredients are to be released.

The transepithelial transport is quantified by measuring the analyte concentration in the basal compartment and calculation of the apparent transport coefficient (P_app).

Analysis:

The marker substance of mixtures is analysed at the start of supplementation and after transport on the basal side. The analyses are conducted in-house using UHPLC with optical detection or LC-MS/MS, depending on the analyte.

Substances we analyse include:

• Vitamins
• Polyphenols and flavonoids
• Terpenes
• Curcuminoids
• Silymarin
• Cannabinoids
• Trace elements

PAMPA Assay:

Cell-free alternative for determining the passive permeation of active substances through an artificial membrane.