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Effect of Elevated pH on the Commercial Enteric-Coated Omeprazole Pellets Resistance: Patent Review and Multisource Generics Comparison

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Abstract

Omeprazole is a widely used over-the-counter (20 mg) proton pump inhibitor, usually supplied as oral enteric-coated pellets intended to release at pH 5.5 and higher; however, it is sensitive to acidic pH. The likelihood of elevated gastric pH in practice is very high for patients; thus, the aim of this study was to investigate the effect of elevated pH on the performance of commercial omeprazole pellets. Commercial enteric-coated delayed-release pellets were tested with water uptake-weight loss (WU-WL) test at pH range between 1.2 and 4.5 in addition to “gastric” (pH 1.2 or 4.5) and “intestinal” (pH 7.4) phase dissolution tests. The range of physical characteristics of pellets was determined with a single pellet size and sedimentation time measurement, followed by the application of modified Stokes’ Law equation. The coefficient of variation of pellet size and density, and volume-density determination coefficient (R2) as descriptors of coating thickness and microstructure variability, degree of ionisation of enteric polymers, aqueous solubility and molecular weight of plasticisers have been found useful to explain commercial delayed-release pellets behaviour during WU-WL and dissolution test. Investigated commercial delayed-release pellets demonstrated pH-dependent WU-WL results. “Gastric phase” dissolution testing of pellets at pH 4.5 showed the highest omeprazole degradation (48.1%) for Nosch Labs, intermediate values of dose loss (23.4% and 17.1%) for Teva and UQUIFA delayed-release pellets, respectively. Lab Liconsa pellets have been found as the least susceptible (3.2% of dose loss). Additionally, “gastric phase” dissolution test at pH 4.5 significantly influenced omeprazole release during the “intestinal phase”. The risk of inadequate therapy associated with intake of investigated enteric-coated delayed-release pellets at elevated gastric pH has been found as minimal for Lab Liconsa and has increased from UQUIFA and Teva to Nosh Labs pellets.

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Acknowledgements

The authors want to thank Maryna Grokholska (Head of Quality Control Department at PrJSC “INDAR”, Kyiv, Ukraine) for her valuable help.

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Authors and Affiliations

  1. School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK

    Valentyn Mohylyuk

  2. Department of Biomedical Technology, Open International University of Human Development “Ukraine”, 23 Lvivska St, Kyiv, 03115, Ukraine

    Anna Yerkhova & Marina Katynska

  3. PrJSC “INDAR”, 5 Zroshuvalna St, Kyiv, 02099, Ukraine

    Vitaliy Sirko

  4. Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, College Ln, Hatfield, AL10 9AB, UK

    Kavil Patel

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Mohylyuk, V., Yerkhova, A., Katynska, M. et al. Effect of Elevated pH on the Commercial Enteric-Coated Omeprazole Pellets Resistance: Patent Review and Multisource Generics Comparison. AAPS PharmSciTech 22, 188 (2021). https://doi.org/10.1208/s12249-021-02038-2

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