Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis
The aim of this study was to understand drug solubilization as a function of age and identify drugs at risk of altered drug solubility in newborns and young infants in comparison to adults. Multivariate statistical analysis was used to understand drug solubilization as a function of drug’s physicoch...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/356 |
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| author | Mariana Guimarães Anil Maharaj Andrea Edginton Maria Vertzoni Nikoletta Fotaki |
| author_facet | Mariana Guimarães Anil Maharaj Andrea Edginton Maria Vertzoni Nikoletta Fotaki |
| author_sort | Mariana Guimarães |
| collection | DOAJ |
| description | The aim of this study was to understand drug solubilization as a function of age and identify drugs at risk of altered drug solubility in newborns and young infants in comparison to adults. Multivariate statistical analysis was used to understand drug solubilization as a function of drug’s physicochemical properties and the composition of gastrointestinal fluids. The solubility of seven poorly soluble compounds was assessed in adult and age-specific fasted and fed state biorelevant media. Partial least squares regression (PLS-R) was used to assess the influence of (i) drug physicochemical properties and (ii) age-related changes in simulated GI fluids, as well as (iii) their interactions, on the pediatrics-to-adult solubility ratio (Sp/Sa (%)). For five out of seven of the compounds investigated, Sp/Sa (%) values fell outside of the 80–125% limits in at least one of the pediatric media. Lipophilicity was responsible for driving drug solubility differences between adults and children in all the biorelevant media investigated, while drug ionization was most relevant in the fed gastric media, and the fasted/fed intestinal media. The concentration of bile salts and lecithin in the fasted and fed intestinal media was critical in influencing drug solubility, while food composition (i.e., cow’s milk formula vs. soy formula) was a critical parameter in the fed gastric state. Changes in GI fluid composition between younger pediatric patients and adults can significantly alter drug luminal solubility. The use of pediatric biorelevant media can be helpful to identify the risk of altered drug solubilization in younger patients during drug development. |
| first_indexed | 2024-03-09T21:14:17Z |
| format | Article |
| id | doaj.art-bdd0f313019c45888427bcccd1f70ac5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:14:17Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-bdd0f313019c45888427bcccd1f70ac52023-11-23T21:37:56ZengMDPI AGPharmaceutics1999-49232022-02-0114235610.3390/pharmaceutics14020356Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data AnalysisMariana Guimarães0Anil Maharaj1Andrea Edginton2Maria Vertzoni3Nikoletta Fotaki4Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UKFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, CanadaSchool of Pharmacy, University of Waterloo, Waterloo, ON N2G 1C5, CanadaDepartment of Pharmacy, National and Kapodistrian University of Athens, 157 72 Athens, GreeceDepartment of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UKThe aim of this study was to understand drug solubilization as a function of age and identify drugs at risk of altered drug solubility in newborns and young infants in comparison to adults. Multivariate statistical analysis was used to understand drug solubilization as a function of drug’s physicochemical properties and the composition of gastrointestinal fluids. The solubility of seven poorly soluble compounds was assessed in adult and age-specific fasted and fed state biorelevant media. Partial least squares regression (PLS-R) was used to assess the influence of (i) drug physicochemical properties and (ii) age-related changes in simulated GI fluids, as well as (iii) their interactions, on the pediatrics-to-adult solubility ratio (Sp/Sa (%)). For five out of seven of the compounds investigated, Sp/Sa (%) values fell outside of the 80–125% limits in at least one of the pediatric media. Lipophilicity was responsible for driving drug solubility differences between adults and children in all the biorelevant media investigated, while drug ionization was most relevant in the fed gastric media, and the fasted/fed intestinal media. The concentration of bile salts and lecithin in the fasted and fed intestinal media was critical in influencing drug solubility, while food composition (i.e., cow’s milk formula vs. soy formula) was a critical parameter in the fed gastric state. Changes in GI fluid composition between younger pediatric patients and adults can significantly alter drug luminal solubility. The use of pediatric biorelevant media can be helpful to identify the risk of altered drug solubilization in younger patients during drug development.https://www.mdpi.com/1999-4923/14/2/356biopharmaceuticspediatricbiorelevantsolubilitymultivariate analysis |
| spellingShingle | Mariana Guimarães Anil Maharaj Andrea Edginton Maria Vertzoni Nikoletta Fotaki Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis Pharmaceutics biopharmaceutics pediatric biorelevant solubility multivariate analysis |
| title | Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis |
| title_full | Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis |
| title_fullStr | Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis |
| title_full_unstemmed | Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis |
| title_short | Understanding the Impact of Age-Related Changes in Pediatric GI Solubility by Multivariate Data Analysis |
| title_sort | understanding the impact of age related changes in pediatric gi solubility by multivariate data analysis |
| topic | biopharmaceutics pediatric biorelevant solubility multivariate analysis |
| url | https://www.mdpi.com/1999-4923/14/2/356 |
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