Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprolol
Abstract Merck KGaA observed slight differences in the dissolution of Concor® (bisoprolol) batches over the years. The purpose of this work was to assess the impact of in vitro dissolution on the simulated pharmacokinetics of bisoprolol using in vitro–in vivo relationship established with available...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-06-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.12634 |
| _version_ | 1818644862272012288 |
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| author | Joyce S. Macwan Grace Fraczkiewicz Mauro Bertolino Phillip Krüger Sheila‐Annie Peters |
| author_facet | Joyce S. Macwan Grace Fraczkiewicz Mauro Bertolino Phillip Krüger Sheila‐Annie Peters |
| author_sort | Joyce S. Macwan |
| collection | DOAJ |
| description | Abstract Merck KGaA observed slight differences in the dissolution of Concor® (bisoprolol) batches over the years. The purpose of this work was to assess the impact of in vitro dissolution on the simulated pharmacokinetics of bisoprolol using in vitro–in vivo relationship established with available in vitro dissolution and corresponding plasma concentrations‐time data for several bisoprolol batches. A mechanistic absorption model/physiologically based pharmacokinetics model linked with a biopharmaceutics tool such as dissolution testing, namely, physiologically based biopharmaceutics modeling (PBBM), can be valuable in determining a dissolution “safe space.” A PBBM for bisoprolol was built using in vitro, in silico, and clinical data. We evaluated potential influences of variability in dissolution of bisoprolol batches on its clinical performance through PBBM and virtual bioequivalence (BE) trials. We demonstrated that in vitro dissolution was not critical for the clinical performance of bisoprolol over a wide range of tested values. Based on virtual BE trials, safe space expansion was explored using hypothetical dissolution data. A formulation with in vitro dissolution reaching 70% dissolved in 15 min and 79.5% in 30 min was shown to be BE to classical fast dissolution of bisoprolol (>85% within 15 min), as point estimates and 90% confidence intervals of the maximum plasma concentration and area under the concentration‐time curve were within the BE limits (0.8–1.25). |
| first_indexed | 2024-12-17T00:21:35Z |
| format | Article |
| id | doaj.art-5c4526a3e83545c88387d95bf5d2e5c2 |
| institution | Directory Open Access Journal |
| issn | 2163-8306 |
| language | English |
| last_indexed | 2024-12-17T00:21:35Z |
| publishDate | 2021-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj.art-5c4526a3e83545c88387d95bf5d2e5c22022-12-21T22:10:33ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062021-06-0110662263210.1002/psp4.12634Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprololJoyce S. Macwan0Grace Fraczkiewicz1Mauro Bertolino2Phillip Krüger3Sheila‐Annie Peters4Simulations Plus, Inc Lancaster California USASimulations Plus, Inc Lancaster California USAQuantitative Pharmacology Merck KGaA Darmstadt GermanyManufacturing Science and Technology Merck KGaA Darmstadt GermanyQuantitative Pharmacology Merck KGaA Darmstadt GermanyAbstract Merck KGaA observed slight differences in the dissolution of Concor® (bisoprolol) batches over the years. The purpose of this work was to assess the impact of in vitro dissolution on the simulated pharmacokinetics of bisoprolol using in vitro–in vivo relationship established with available in vitro dissolution and corresponding plasma concentrations‐time data for several bisoprolol batches. A mechanistic absorption model/physiologically based pharmacokinetics model linked with a biopharmaceutics tool such as dissolution testing, namely, physiologically based biopharmaceutics modeling (PBBM), can be valuable in determining a dissolution “safe space.” A PBBM for bisoprolol was built using in vitro, in silico, and clinical data. We evaluated potential influences of variability in dissolution of bisoprolol batches on its clinical performance through PBBM and virtual bioequivalence (BE) trials. We demonstrated that in vitro dissolution was not critical for the clinical performance of bisoprolol over a wide range of tested values. Based on virtual BE trials, safe space expansion was explored using hypothetical dissolution data. A formulation with in vitro dissolution reaching 70% dissolved in 15 min and 79.5% in 30 min was shown to be BE to classical fast dissolution of bisoprolol (>85% within 15 min), as point estimates and 90% confidence intervals of the maximum plasma concentration and area under the concentration‐time curve were within the BE limits (0.8–1.25).https://doi.org/10.1002/psp4.12634 |
| spellingShingle | Joyce S. Macwan Grace Fraczkiewicz Mauro Bertolino Phillip Krüger Sheila‐Annie Peters Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprolol CPT: Pharmacometrics & Systems Pharmacology |
| title | Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprolol |
| title_full | Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprolol |
| title_fullStr | Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprolol |
| title_full_unstemmed | Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprolol |
| title_short | Application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products: The case of bisoprolol |
| title_sort | application of physiologically based biopharmaceutics modeling to understand the impact of dissolution differences on in vivo performance of immediate release products the case of bisoprolol |
| url | https://doi.org/10.1002/psp4.12634 |
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