Critical Quality Attributes of Acyclovir Topical Creams: Characterization of Quality Attributes with Relevance to Topical Bioavailability.

PURPOSE: To characterize the quality (Q3) attributes of selected acyclovir topical creams and evaluate their relationship with topical bioavailability, as determined by in vitro permeation testing (IVPT).

METHODS

The Q3 attributes of five commercially available acyclovir cream products were comprehensively characterized. The formulations were then evaluated using IVPT across human cadaver skin. The Q3 attributes of the reference listed drugs (RLDs) approved in the USA, UK, and Austria, and generic products approved in Austria were compared and correlated with their permeation profiles.

RESULTS

The rate and extent of acyclovir permeation were comparable among cream products with similar Q3 attributes. Conversely, formulations exhibiting differences in Q3 attributes demonstrated significantly different topical bioavailability. Overall, IVPT performance correlated well with differences in the Q3 attributes of the formulations.

CONCLUSIONS

This study demonstrates a strong association between Q3 attributes and the topical bioavailability of acyclovir creams. Comparable Q3 attributes predicted comparable in vitro performance, whereas differences in Q3 attributes resulted in significantly different permeation profiles. These findings support the importance of comprehensive Q3 characterization as a critical component in the development and regulatory assessment of topical drug products.