(T0930-06-33) Impact of Apparatus and Adaptor Setups on In Vitro Drug Release of Ophthalmic Semi-solid Drug Products

Purpose: In vitro release testing (IVRT) is a useful tool for evaluating drug product quality and performance. For complex formulations such as ophthalmic ointments, there are currently no standardized sample adaptors or drug release apparatus setups for IVRT studies. The aim of this study was to provide a better understanding of the impact of apparatus and sample adaptor setups on in vitro drug release of ophthalmic ointments.

Methods: Dexamethasone (DEX), a common steroid in ophthalmic products, was selected as a model drug. DEX ointments containing 0.2% of DEX, 5% of mineral oil, 0.5% of chlorobutanol, and 94.3% of petrolatum were prepared using a high shear mixer. A novel two-sided adapter was developed to enlarge the release surface area. DEX ointment was placed in one-sided or two-sided release adaptors coupled with 1.2 mm polyethersulfone membrane, and the drug release was studied in different USP apparatuses (I, II and IV). DEX concentrations in the release samples at various timepoints were determined by HPLC analysis. The cumulative drug release (µg/cm²) was plotted against logarithm of time or square root of time. Slope and R² were obtained from the linear regression.

Results: The novel two-sided semisolid adapter showed release profiles with less variation compared with one-sided adapters (Figure 1). The exposed surface areas did not significantly affect drug release rate. However, release rates obtained using different apparatuses exhibited significant differences (Figure 2), which may be due to different flow properties of the medium on the surface of the ointments/adapters. For example, the rapid flow of media in the USP apparatus IV may be responsible for the observed enhanced release rates. When using USP apparatus I, the two-sided release adapter showed a higher percent cumulative drug release compared to the one-sided adapters, but slight lower release rates.

Conclusion: The apparatus used for IVRT can influence the drug release profile from ophthalmic ointment. The sample adaptor setups had a minimal impact on cumulative drug release amount per area or release rate while USP apparatus IV with agitated flow enhanced drug release rates compared with USP apparatus I. The results from this study can assist researchers in both the pharmaceutical manufacturing and pharmaceutical research sectors to design an apparatus and sample adaptor setup of IVRT for semisolid drug products.

Acknowledgements: The authors would like to acknowledge the U.S. Food and Drug Administration for financial support of this research (contract number: HHSF223201810114C).
Disclaimer: The views expressed in this abstract do not reflect the official policies of the U.S. Food and Drug Administration or the U.S. Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.


Figure 1 In vitro release profiles using PES in both sides of two-sided semisolid adapter in USP apparatus I and one-sided semisolid adapter in USP apparatus IV (n=3)


Figure 2 In vitro release of dexamethasone using one-sided semisolid adapter in USP apparatus II and IV (n=3)