Evaluation of the in vitro performance of generic and original adapalene gel.

OBJECTIVE: The aim was to evaluate the difference of the in vitro behavior between the commercially available generic adapalene gel and original product with Topical Classification System (TCS), and to analyze the effect of changes of excipients on the release behavior. SIGNIFICANCE: Establishing in vitro performance assays to understand the impact of formulation variables on the critical quality attributes (CQA) is critical for the quality assessment of semi-solid generic drug. METHODS: In vitro release (IVR), in vitro permeation (IVP), viscosity, and pH measurement methods for adapalene gels were established and validated. The differences between generic adapalene gel from 7 companies and original products were evaluated by correlation analysis (CA) and principal component analysis (PCA), and the relationship among 4 parameters was elucidated. The effect of excipients on the above variables was examined by univariate tests. RESULTS: There were some differences between the gels of 5 of the 7 imitation enterprises and reference listed drug (RLD). There were varying degrees of correlation between viscosity, pH, the adapalene amount retained in skin and release rate. The result validated the key role of IVR, and identified that pH value, type of suspending agent, the amount of carbomer, etc. had certain effects on the release rate. CONCLUSIONS: The factors mentioned above should be considered when developing and manufacturing generic adapalene gels, and the application of TCS in the evaluation of generic topical drugs was advanced. Additionally, our research revealed some discrepancies from USP<1724>, which could be valuable information for the revision.