IVPT — In Vitro Permeation Testing

IVPT is a laboratory method that measures how much of an active ingredient permeates through skin from a topically applied product over time. Excised human or animal skin is mounted in a diffusion cell, the product is applied to the surface, and the amount of drug reaching the receptor fluid beneath the skin is measured at set intervals.

The result is a permeation profile — flux and cumulative amount permeated — that characterizes how a topical or transdermal product delivers drug across the skin barrier.

IVRT (In Vitro Release Testing) measures the rate at which an active ingredient is released from a topical formulation across a synthetic membrane, characterizing the product itself. IVPT (In Vitro Permeation Testing) measures how much active ingredient permeates through actual skin, characterizing delivery to and through the skin barrier.

In short: IVRT reflects formulation release, IVPT reflects biologically relevant skin penetration. Many topical development and bioequivalence programs use both.

IVPT studies most often use excised human skin, which is the most biologically relevant barrier, and porcine skin, a well-accepted surrogate with a barrier similar to human skin. Skin is typically prepared as dermatomed or split-thickness sections and mounted in Franz-type diffusion cells.

The choice of skin source and preparation depends on the product, the scientific question, and any applicable regulatory expectations.

A Franz diffusion cell is the standard apparatus for IVRT and IVPT. It has a donor chamber on top and a receptor chamber below, separated by the membrane or skin sample. The test product is applied to the skin in the donor chamber, and receptor fluid below is sampled over time to measure how much drug has permeated. Temperature and stirring are controlled to mimic physiological conditions.

For many topical generic products, demonstrating equivalent drug delivery by conventional blood-level pharmacokinetics is difficult, because systemic exposure is often very low. IVPT can provide a sensitive, discriminating comparison of how much active ingredient permeates skin from a test versus a reference product, supporting bioequivalence assessments.

Regulators including the FDA reference in vitro permeation approaches in product-specific guidances for certain topical products; specific requirements vary by product and should be confirmed against current regulatory guidance.

Q1 means a product has the same components as the reference, Q2 means the same components at the same concentrations, and Q3 means the same arrangement of matter — comparable physical and structural properties (microstructure).

IVPT and IVRT are commonly used to support Q3 equivalence, because differences in microstructure can change how a drug is released and permeates even when Q1 and Q2 are matched.

Regulatory-grade IVPT studies are typically run across multiple skin donors with several replicate cells per donor, so that both within-donor and between-donor variability are captured in the statistical comparison.

The exact number depends on the study objective and the applicable regulatory expectation; a study designed for regulatory submission generally uses more donors and replicates than an exploratory formulation-screening study.

Yes. Beyond regulatory bioequivalence work, IVPT is valuable during formulation development — for screening prototype formulations, optimizing drug delivery, comparing excipient effects, and understanding how formulation changes affect skin penetration. Using IVPT early can reduce risk before committing to a final formulation or a clinical program.

IVPT is used for topical products that act in or on the skin and for transdermal products intended to deliver drug into systemic circulation. Related diffusion-cell methods can also characterize delivery across other barriers, such as nail (for onychomycosis products) and mucosal tissue, depending on the product and target site.

Zelmic, based in Lund, Sweden, is a specialized CRO/CDMO offering IVRT and IVPT alongside topical and transdermal formulation development, analytical chemistry and EU GMP manufacturing. Zelmic performs IVPT using Franz diffusion cells with human and porcine skin and supports formulation development, optimization and regulatory programs for topical and transdermal products.