On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development
A small-scale biphasic dissolution setup and a small-scale dissolution-permeation (D-P) setup were evaluated for their usefulness in simulating the luminal precipitation of three lipophilic weak bases—dipyridamole, ketoconazole and itraconazole. The transition from the gastric to intestina...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/3/272 |
| _version_ | 1828150968914542592 |
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| author | Patrick J. O’Dwyer Georgios Imanidis Karl J. Box Christos Reppas |
| author_facet | Patrick J. O’Dwyer Georgios Imanidis Karl J. Box Christos Reppas |
| author_sort | Patrick J. O’Dwyer |
| collection | DOAJ |
| description | A small-scale biphasic dissolution setup and a small-scale dissolution-permeation (D-P) setup were evaluated for their usefulness in simulating the luminal precipitation of three lipophilic weak bases—dipyridamole, ketoconazole and itraconazole. The transition from the gastric to intestinal environment was incorporated into both experimental procedures. Emulsification during the biphasic dissolution experiments had a minimal impact on the data, when appropriate risk mitigation steps were incorporated. Precipitation parameters estimated from the in vitro data were inputted into the Simcyp<sup>®</sup> physiologically based pharmacokinetic (PBPK) modelling software and simulated human plasma profiles were compared with previously published pharmacokinetic data. Average C<sub>max</sub> and AUC values estimated using experimentally derived precipitation parameters from the biphasic experiments deviated from corresponding published actual values less than values estimated using the default simulator parameters for precipitation. The slow rate of transport through the biomimetic membrane in the D-P setup limited its usefulness in forecasting the rates of in vivo precipitation used in the modelling of average plasma profiles. |
| first_indexed | 2024-04-11T21:50:31Z |
| format | Article |
| id | doaj.art-654759486b4e406f93bd46e1917a97b0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T21:50:31Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-654759486b4e406f93bd46e1917a97b02022-12-22T04:01:15ZengMDPI AGPharmaceutics1999-49232020-03-0112327210.3390/pharmaceutics12030272pharmaceutics12030272On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation DevelopmentPatrick J. O’Dwyer0Georgios Imanidis1Karl J. Box2Christos Reppas3Pion Inc. (UK) Ltd., Forest Row, East Sussex RH18 5DW, UKSchool of Life Sciences, Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, Hofackerstrasse 30, 4132 Muttenz, SwitzerlandPion Inc. (UK) Ltd., Forest Row, East Sussex RH18 5DW, UKDepartment of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, GR 157 84 Zografou, GreeceA small-scale biphasic dissolution setup and a small-scale dissolution-permeation (D-P) setup were evaluated for their usefulness in simulating the luminal precipitation of three lipophilic weak bases—dipyridamole, ketoconazole and itraconazole. The transition from the gastric to intestinal environment was incorporated into both experimental procedures. Emulsification during the biphasic dissolution experiments had a minimal impact on the data, when appropriate risk mitigation steps were incorporated. Precipitation parameters estimated from the in vitro data were inputted into the Simcyp<sup>®</sup> physiologically based pharmacokinetic (PBPK) modelling software and simulated human plasma profiles were compared with previously published pharmacokinetic data. Average C<sub>max</sub> and AUC values estimated using experimentally derived precipitation parameters from the biphasic experiments deviated from corresponding published actual values less than values estimated using the default simulator parameters for precipitation. The slow rate of transport through the biomimetic membrane in the D-P setup limited its usefulness in forecasting the rates of in vivo precipitation used in the modelling of average plasma profiles.https://www.mdpi.com/1999-4923/12/3/272precipitationsupersaturationbiorelevantin vitro techniquespbpk modellingbiphasic dissolutiondissolution-permeation |
| spellingShingle | Patrick J. O’Dwyer Georgios Imanidis Karl J. Box Christos Reppas On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development Pharmaceutics precipitation supersaturation biorelevant in vitro techniques pbpk modelling biphasic dissolution dissolution-permeation |
| title | On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development |
| title_full | On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development |
| title_fullStr | On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development |
| title_full_unstemmed | On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development |
| title_short | On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development |
| title_sort | on the usefulness of two small scale in vitro setups in the evaluation of luminal precipitation of lipophilic weak bases in early formulation development |
| topic | precipitation supersaturation biorelevant in vitro techniques pbpk modelling biphasic dissolution dissolution-permeation |
| url | https://www.mdpi.com/1999-4923/12/3/272 |
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