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Development and Validation of Sample Preparation and an HPLC Analytical Method for Dissolution Testing in Fed-State Simulated Gastric Fluid—Illustrating Its Application for Ibuprofen and Ketoconazole Immediate Release Tablets

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  • Theme: Team Science and Education for Pharmaceuticals: the NIPTE Model
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Abstract

Dissolution testing and solubility determinations in different biorelevant media have gained considerable interest in the pharmaceutical industry from early-stage development of new products to forecasting bioequivalence. Among all biorelevant fluids, the preparation of fed-state simulated gastric fluid (FeSSGF) and handling of samples from dissolution/solubility testing in FeSSGF is considered to be relatively challenging. Challenges include maintaining the stability of FeSSGF medium upon sampling, filtration, and mitigating analytical interference of excipients and milk components. To overcome these challenges, standard and uniform working practices are required that are not only helpful in preparation of stable FeSSGF but also serve as a harmonizing guide for the collection of dissolution/solubility samples and their subsequent processing (i.e., handling and assay). The optimization of sample preparation methodology is crucial to reduce method-related variance by ensuring specificity, robustness, and reproducibility with acceptable recovery of the analytes. The sample preparation methodology includes a combination of techniques including filtration, solvent treatment, and centrifugation to remove the interfering media-related components and excipients from the analyte. The analytes of interest were chromatographically separated from the interfering analytes to quantify the drug concentration using the new high-performance liquid chromatography methods with ultraviolet detection. The methods developed allow rapid sample preparation, acceptable specificity, reproducible recoveries (greater than 95% of label claim), and quantification of study drugs (ibuprofen and ketoconazole). The sample preparation technique and method considerations provided here for ibuprofen and ketoconazole can serve as a starting point for solubility and dissolution testing of other small molecules in FeSSGF.

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Disclaimer

The approaches and conclusions reported in this publication have not been formally disseminated by the US Food and Drug Administration and should not be construed to represent any Agency determination or policy.

Funding

We gratefully acknowledge the US Food and Drug Administration (USFDA) and the National Institute for Pharmaceutical technology and Education (NIPTE) for financial support. This study was funded by the FDA Grant to NIPTE titled “The Critical Path Manufacturing Sector Research Initiative (U01)”; Grant No. 5U01FD004275.

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Authors and Affiliations

  1. Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn Campus, 75 DeKalb Avenue, Room WL 313, Brooklyn, New York, NY, 11201, USA

    Harsh S. Shah, Rusha Sardhara, Kajal Nahar & Kenneth Morris

  2. Triclinic Labs, 2660 Schuyler Ave Ste A, Lafayette, IN, 47905, USA

    Ting Xu

  3. United States Food and Drug Administration, Center for Drug Evaluation and Research/Office of Pharmaceutical Quality, Silver Spring, MD, 20993, USA

    Poonam Delvadia, Akhtar Siddiqui & Arzu Selen

  4. United States Food and Drug Administration, Center for Drug Evaluation and Research/Office of Pharmaceutical Quality, St. Louis, MO, 63110, USA

    Zongming Gao

  5. Lachman Institute for Pharmaceutical Analysis, Long Island University, Brooklyn, New York, NY, 11201, USA

    Kenneth Morris

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  1. Harsh S. Shah
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Correspondence to Kenneth Morris.

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Guest Editors: Ajaz S. Hussain, Kenneth Morris, and Vadim J. Gurvich

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Shah, H.S., Sardhara, R., Nahar, K. et al. Development and Validation of Sample Preparation and an HPLC Analytical Method for Dissolution Testing in Fed-State Simulated Gastric Fluid—Illustrating Its Application for Ibuprofen and Ketoconazole Immediate Release Tablets. AAPS PharmSciTech 21, 172 (2020). https://doi.org/10.1208/s12249-020-01702-3

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