Semisolid Drug Product Quality and Performance Tests

The USP adopted the revised general chapters <1724> Semisolid Drug Products - Performance Tests and <1912> Measurement of Yield Stress of Semisolids. The two chapters were previously published for comment in Pharmacopeial Forum PF 48(3). The final versions have been published in USP-NF 2023 Issue 3 (to be official on 1 December 2023).

Background and Updates

<1724> Semisolid Drug Products - Performance Tests

The chapter <1724> provides general information about developing in vitro performance tests to evaluate drug release or skin permeation for topical and transdermal semisolid and liquid-based dosage forms, like, creams, gels, ointments, pastes, suspensions, lotions, and foams. Compared to the currently valid version, the scope of <1724> has been expanded. It now includes in vitro release test (IVRT) as well as in vitro permeation test (IVPT) methods, with discussions on experimental design, method development, and validation. In addition, new information is included on appropriate contexts of use for IVRT and IVPT studies, and a guide for selecting an appropriate test method (IVRT or IVPT) depending upon the goal of the experiment. Reference is made to the FDA Guidance Nonsterile Semisolid Dosage Forms; Scale-Up and Postapproval CMC Changes; In Vitro Release Testing and In Vivo Bioequivalence Documentation. For example,

• IVRT studies may provide evidence to support equivalence demonstration between changes of a product, or to support a demonstration of bioequivalence in certain situations.
• IVPT studies can be sensitive and discriminating to differences in the rate and extent to which compounds applied on the skin from different formulations become available in and through it. Unlike IVRT studies, differences in permeation that are observed in an IVPT study comparing a test versus reference product may correlate with and/or be predictive of differences in bioavailability in vivo. Thus, the IVPT is routinely carried out to guide semi-solid topical formulation development.

<1912> Measurement of Yield Stress of Semisolids

According to the USP, "characterizing and monitoring the viscoelastic properties of semisolids is not straightforward because the properties can be dominated by either solid- or liquid-like behavior depending on how much deformation or stress is applied". If the performance of a semisolid raw material (e.g. wool fat, petrolatum) or dosage form (e.g. ointment, cream) is primarily dependent on the behavior under high-shear conditions, then viscosity may be an appropriate parameter to monitor. However, if the properties of the raw material or dosage form are critical at low shear or at rest, then measurement of the yield stress may be required. The revised chapter <1912> provides a brief summary of the mathematical models used to quantify the viscoelastic properties of semisolids, followed by a summary of the most common experimental methods. In addition, the title of <1912> has been updated (the previous title was "Measurement of Hardness of Semisolids") and the glossary now includes a definition for yield stress.

Accordingly, the references to <1912> contained in the two general chapters <3> Topical and Transdermal Drug Products-Product Quality Tests and <915> Measurement of Structural Strength of Semisolids by Penetrometry have been updated.

More information is available in the USP-NF.