Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients
Some years ago, excipients were considered inert substances irrelevant in the absorption process. However, years of study have demonstrated that this belief is not always true. In this study, the reasons for a bioequivalence failure between two formulations of silodosin are investigated. Silodosin i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/12/2565 |
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| author | Isabel González-Álvarez Bárbara Sánchez-Dengra Raquel Rodriguez-Galvez Alejandro Ruiz-Picazo Marta González-Álvarez Alfredo García-Arieta Marival Bermejo |
| author_facet | Isabel González-Álvarez Bárbara Sánchez-Dengra Raquel Rodriguez-Galvez Alejandro Ruiz-Picazo Marta González-Álvarez Alfredo García-Arieta Marival Bermejo |
| author_sort | Isabel González-Álvarez |
| collection | DOAJ |
| description | Some years ago, excipients were considered inert substances irrelevant in the absorption process. However, years of study have demonstrated that this belief is not always true. In this study, the reasons for a bioequivalence failure between two formulations of silodosin are investigated. Silodosin is a class III drug according to the Biopharmaceutics Classification System, which has been experimentally proven by means of solubility and permeability experiments. Dissolution tests have been performed to identify conditions concordant with the non-bioequivalent result obtained from the human bioequivalence study and it has been observed that paddles at 50 rpm are able to detect inconsistent differences between formulations at pH 4.5 and pH 6.8 (which baskets at 100 rpm are not able to do), whereas the GIS detects differences at the acidic pH of the stomach. It has also been observed that the differences in excipients between products did not affect the disintegration process, but disintegrants did alter the permeability of silodosin through the gastrointestinal barrier. Crospovidone and povidone, both derivatives of PVP, are used as disintegrants in the test product, instead of the pregelatinized corn starch used in the reference product. Permeability experiments show that PVP increases the absorption of silodosin—an increase that would explain the greater C<sub>max</sub> observed for the test product in the bioequivalence study. |
| first_indexed | 2024-03-09T15:58:43Z |
| format | Article |
| id | doaj.art-c59935dd1d544a3f870878e72c51ca57 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T15:58:43Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c59935dd1d544a3f870878e72c51ca572023-11-24T17:18:08ZengMDPI AGPharmaceutics1999-49232022-11-011412256510.3390/pharmaceutics14122565Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant ExcipientsIsabel González-Álvarez0Bárbara Sánchez-Dengra1Raquel Rodriguez-Galvez2Alejandro Ruiz-Picazo3Marta González-Álvarez4Alfredo García-Arieta5Marival Bermejo6Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, 03550 San Juan de Alicante, SpainEngineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, 03550 San Juan de Alicante, SpainEngineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, 03550 San Juan de Alicante, SpainEngineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, 03550 San Juan de Alicante, SpainEngineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, 03550 San Juan de Alicante, SpainService of Pharmacokinetics and Generic Medicines, Division of Pharmacology and Clinical Evaluation, Department of Human Use Medicines, Spanish Agency for Medicines and Health Care Products, 28022 Madrid, SpainEngineering: Pharmacokinetics and Pharmaceutical Technology Area, Miguel Hernandez University, 03550 San Juan de Alicante, SpainSome years ago, excipients were considered inert substances irrelevant in the absorption process. However, years of study have demonstrated that this belief is not always true. In this study, the reasons for a bioequivalence failure between two formulations of silodosin are investigated. Silodosin is a class III drug according to the Biopharmaceutics Classification System, which has been experimentally proven by means of solubility and permeability experiments. Dissolution tests have been performed to identify conditions concordant with the non-bioequivalent result obtained from the human bioequivalence study and it has been observed that paddles at 50 rpm are able to detect inconsistent differences between formulations at pH 4.5 and pH 6.8 (which baskets at 100 rpm are not able to do), whereas the GIS detects differences at the acidic pH of the stomach. It has also been observed that the differences in excipients between products did not affect the disintegration process, but disintegrants did alter the permeability of silodosin through the gastrointestinal barrier. Crospovidone and povidone, both derivatives of PVP, are used as disintegrants in the test product, instead of the pregelatinized corn starch used in the reference product. Permeability experiments show that PVP increases the absorption of silodosin—an increase that would explain the greater C<sub>max</sub> observed for the test product in the bioequivalence study.https://www.mdpi.com/1999-4923/14/12/2565Biopharmaceutics Classification System (BCS)pharmacokinetics (PK)in vitro dissolutionpermeabilitybioequivalence |
| spellingShingle | Isabel González-Álvarez Bárbara Sánchez-Dengra Raquel Rodriguez-Galvez Alejandro Ruiz-Picazo Marta González-Álvarez Alfredo García-Arieta Marival Bermejo Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients Pharmaceutics Biopharmaceutics Classification System (BCS) pharmacokinetics (PK) in vitro dissolution permeability bioequivalence |
| title | Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients |
| title_full | Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients |
| title_fullStr | Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients |
| title_full_unstemmed | Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients |
| title_short | Exploring a Bioequivalence Failure for Silodosin Products Due to Disintegrant Excipients |
| title_sort | exploring a bioequivalence failure for silodosin products due to disintegrant excipients |
| topic | Biopharmaceutics Classification System (BCS) pharmacokinetics (PK) in vitro dissolution permeability bioequivalence |
| url | https://www.mdpi.com/1999-4923/14/12/2565 |
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