Reliability and reproducibility of vertical diffusion cells for determining release rates from semisolid dosage forms

Area of Science:

• Pharmaceutical Sciences
• Metrology
• Drug Delivery Systems

Background:

• The United States Pharmacopeia (USP) is developing performance tests (performance qualification, PQ) for non-oral drug administration routes.
• Performance verification tests (PVT) are integral to PQ, involving collaborative studies to establish acceptance criteria for laboratory tests.
• These studies adhere to metrological principles, such as ISO 43-1, to ensure laboratory competence in testing.

Purpose of the Study:

• To determine the reliability and reproducibility of release rates from semisolid dosage forms using the vertical diffusion cell (VDC).
• To assess the impact of interlaboratory variability and operator training on the consistency of in vitro release testing.

Main Methods:

• Four laboratories conducted two collaborative studies using the vertical diffusion cell (VDC) method.
• Release rates of semisolid topical dosage forms were measured and analyzed for variability.

Main Results:

• The primary source of variability in release rate testing was identified as the interlaboratory component.
• Creams exhibited greater variability in release rates compared to other semisolid dosage forms tested.
• Consistency improved significantly in the second study after implementing operator training, indicating procedural variations were a key factor.

Conclusions:

• In vitro release testing using VDCs can be considered a PVT for topical semisolid dosage forms.
• Operator training is essential for achieving reproducible results in VDC testing.
• A standardized semisolid product and a method for setting acceptance criteria are needed for effective PVT implementation, potentially utilizing SUPAC-SS Guidance.