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Impact of Apparatus and Adapter on In vitro Drug Release of Ophthalmic Semisolid Drug Products

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Abstract

Purpose

In vitro release testing (IVRT) is a widely used tool for evaluating the quality and performance of drug products. However, standardized sample adaptors or drug release apparatus setups for IVRT studies are still lacking for ophthalmic ointments. The aim of this study was to provide a better understanding of the impact of apparatus and sample adaptor setups on IVRT of ophthalmic ointments.

Methods

Dexamethasone (DEX), a steroidal ingredient commonly used in ophthalmic drug products, was selected as a model drug. Ointments were prepared by mixing DEX in white petrolatum using a high shear mixer. A novel two-sided adapter was developed to increase the drug release surface area. DEX ointment was placed in one-sided or two-sided release adaptors coupled with 1.2 μm polyethersulfone membrane, and the drug release was studied in different USP apparatuses (I, II, and IV).

Results

The sample adaptor setups had a minimal impact on cumulative drug release amount per area or release rate while USP IV apparatus with agitated flow enhanced drug release rates. The USP apparatus I with a two-sided semisolid adapter, which uses membranes on both sides, showed dramatically higher cumulative drug release and discriminative release profiles when evaluating ophthalmic formulations.

Conclusions

USP apparatuses and sample adaptors are critical considerations for IVRT. Two-sided semisolid adapter provides higher cumulative release, facilitating the discrimination between low drug content ophthalmic ointment formulations with good sensitivity and repeatability without affecting the drug release rate.

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Data Availability

The authors declare that the data supporting the findings of this study are available within the paper. Should any raw data files be needed in another format, they are available from the corresponding author upon reasonable request.

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Funding

Funding for this project was made possible by the Food and Drug Administration through grant 1U01FD005174–01 and contract HHSF223201810114C. The views expressed in this paper 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.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT, USA

    Catheleeya Mekjaruskul, Pallabita Chowdhury & Xiuling Lu

  2. Integrative Pharmaceuticals and Innovation of Pharmaceutical Technology Research Unit, Faculty of Pharmacy, Mahasarakham University, 44150, Maha Sarakham, Thailand

    Catheleeya Mekjaruskul

  3. Division of Therapeutic Performance I, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA

    André O’Reilly Beringhs, Bin Qin & Yan Wang

Authors
  1. Catheleeya Mekjaruskul
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  2. André O’Reilly Beringhs
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  3. Bin Qin
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  4. Yan Wang
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  5. Pallabita Chowdhury
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  6. Xiuling Lu
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Corresponding author

Correspondence to Xiuling Lu.

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Conflict of Interests

The authors of this journal paper disclose potential conflicts of interest related to the research and findings presented. The invention (two-sided semisolid adapter) described in this paper is licensed to SOTAX Corporation (2400 Computer Drive, Westborough, MA 01581 USA). The author, Dr. Xiuling Lu, may receive royalties or financial benefits from the sale or commercialization of this invention through the licensing agreement with SOTAX Corporation. It is important to note that the study design, data collection, analysis, and interpretation of the results were conducted independently and objectively, without any influence from the potential financial gains. The authors affirm that the conclusions drawn and the information provided in this paper are based on rigorous research and scientific evidence.

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Mekjaruskul, C., O’Reilly Beringhs, A., Qin, B. et al. Impact of Apparatus and Adapter on In vitro Drug Release of Ophthalmic Semisolid Drug Products. Pharm Res 40, 2239–2251 (2023). https://doi.org/10.1007/s11095-023-03586-x

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  • DOI: https://doi.org/10.1007/s11095-023-03586-x

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