Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs
Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, perm...
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MDPI AG
2025-04-01
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| Series: | Scientia Pharmaceutica |
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| Online Access: | https://www.mdpi.com/2218-0532/93/2/19 |
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| author | Vivien Bárdos Rita Szolláth Petra Tőzsér Arash Mirzahosseini Bálint Sinkó Réka Angi Krisztina Takács-Novák |
| author_facet | Vivien Bárdos Rita Szolláth Petra Tőzsér Arash Mirzahosseini Bálint Sinkó Réka Angi Krisztina Takács-Novák |
| author_sort | Vivien Bárdos |
| collection | DOAJ |
| description | Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is crucial for ensuring optimal bioavailability. Carbamazepine, naproxen and pimobendan were chosen as model compounds due to their different acid–base properties. Equilibrium solubility was measured by the traditional shake flask method. Effective permeability was determined by the PAMPA model. Measurements of ionizable compounds were carried out at three pH values. The pH-dependent change in the investigated parameters is maintained even in the presence of excipients. Fillers resulted in a slight or no effect, while the impact of other excipients showed a significant concentration dependence. The impact of excipients was influenced by the structure and ionization state of the molecules. The dominance of the ionized form moderates the impact of excipients. The changes in solubility were more pronounced than in the case of permeability. By examining the effect of the ionization state and interactions with excipients, this work supports the development of formulations that enhance solubility with minimal impacts on permeability. Additionally, it can serve as good basis for preformulation studies and design optimization. |
| format | Article |
| id | doaj-art-8a824afefabb4b669c0f06b14cc20d64 |
| institution | Kabale University |
| issn | 0036-8709 2218-0532 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Scientia Pharmaceutica |
| spelling | doaj-art-8a824afefabb4b669c0f06b14cc20d642025-08-20T03:29:48ZengMDPI AGScientia Pharmaceutica0036-87092218-05322025-04-019321910.3390/scipharm93020019Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II DrugsVivien Bárdos0Rita Szolláth1Petra Tőzsér2Arash Mirzahosseini3Bálint Sinkó4Réka Angi5Krisztina Takács-Novák6Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, H-1092 Budapest, HungaryDepartment of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, H-1092 Budapest, HungaryDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 3 Műegyetem rkp., H-1111 Budapest, HungaryDepartment of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, H-1092 Budapest, HungaryPion Inc., 10 Cook Street, Billerica, MA 01821, USADepartment of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, H-1092 Budapest, HungaryDepartment of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, H-1092 Budapest, HungaryMost novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is crucial for ensuring optimal bioavailability. Carbamazepine, naproxen and pimobendan were chosen as model compounds due to their different acid–base properties. Equilibrium solubility was measured by the traditional shake flask method. Effective permeability was determined by the PAMPA model. Measurements of ionizable compounds were carried out at three pH values. The pH-dependent change in the investigated parameters is maintained even in the presence of excipients. Fillers resulted in a slight or no effect, while the impact of other excipients showed a significant concentration dependence. The impact of excipients was influenced by the structure and ionization state of the molecules. The dominance of the ionized form moderates the impact of excipients. The changes in solubility were more pronounced than in the case of permeability. By examining the effect of the ionization state and interactions with excipients, this work supports the development of formulations that enhance solubility with minimal impacts on permeability. Additionally, it can serve as good basis for preformulation studies and design optimization.https://www.mdpi.com/2218-0532/93/2/19BCS II APIspharmaceutical excipientsSSFPAMPAequilibrium solubilityintestinal permeability |
| spellingShingle | Vivien Bárdos Rita Szolláth Petra Tőzsér Arash Mirzahosseini Bálint Sinkó Réka Angi Krisztina Takács-Novák Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs Scientia Pharmaceutica BCS II APIs pharmaceutical excipients SSF PAMPA equilibrium solubility intestinal permeability |
| title | Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs |
| title_full | Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs |
| title_fullStr | Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs |
| title_full_unstemmed | Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs |
| title_short | Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs |
| title_sort | study of the influence of pharmaceutical excipients on the solubility and permeability of bcs class ii drugs |
| topic | BCS II APIs pharmaceutical excipients SSF PAMPA equilibrium solubility intestinal permeability |
| url | https://www.mdpi.com/2218-0532/93/2/19 |
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