Complex dispersions of poloxamers and mesoporous carriers with ibrutinib
Ibrutinib is an anticancer drug, a Bruton's tyrosine kinase inhibitor with poor solubility in aqueous media. This study reports on the study of the effectiveness of mesoporous carriers based on magnesium aluminometasilicate and poloxamers to improve the solubility and bioavailability of ibrutin...
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Elsevier
2022-11-01
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| Series: | OpenNano |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352952022000354 |
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| author | Igor A. Dain Sergey A. Zolotov Natalia B. Demina Anna S. Zolotova Grigorii A. Buzanov Vasilii M. Retivov Yevgenii S. Ponomaryov |
| author_facet | Igor A. Dain Sergey A. Zolotov Natalia B. Demina Anna S. Zolotova Grigorii A. Buzanov Vasilii M. Retivov Yevgenii S. Ponomaryov |
| author_sort | Igor A. Dain |
| collection | DOAJ |
| description | Ibrutinib is an anticancer drug, a Bruton's tyrosine kinase inhibitor with poor solubility in aqueous media. This study reports on the study of the effectiveness of mesoporous carriers based on magnesium aluminometasilicate and poloxamers to improve the solubility and bioavailability of ibrutinib in the form of amorphous solid dispersions. The choice of the most effective composition was made on a parallel study of (a) a physical mixture of ibrutinib with a mesoporous carrier, (b) a solid dispersion with a poloxamer on a non-porous carrier, (c) a dispersion with a poloxamer deposited on a mesoporous carrier. Sample mixtures and dispersions with ibrutinib were tested to establish amorphism by various methods and to determine the solubility in aqueous media. The composition of ibrutinib-poloxamer P407-mesoporous carrier showed the best results in three standard media regarding the solubility of ibrutinib (increase in solubility at pH 1.2 - 129.6%, pH 4.5 - 300.2%, pH 6.8 - 363.3%). This composition became the basis for the tablet formulation and showed the best results in the Dissolution test (the dosage was dissolved in only 10 min of the test in pH 1.2 medium by 98.3%, pH 4.5 - 95.4%, pH 6.8 – 57.3%). These results were superior to those of the original Imbruvica capsules at all points in the study. In conclusion, the resulting formulation was stable under accelerated conditions according to the ICH Q1 Quality Guideline (40 °C, 75% relative humidity, 6 months). |
| first_indexed | 2024-04-13T06:17:31Z |
| format | Article |
| id | doaj.art-c4c5f5679258471e89cb36c1a3bffe6b |
| institution | Directory Open Access Journal |
| issn | 2352-9520 |
| language | English |
| last_indexed | 2024-04-13T06:17:31Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | OpenNano |
| spelling | doaj.art-c4c5f5679258471e89cb36c1a3bffe6b2022-12-22T02:58:47ZengElsevierOpenNano2352-95202022-11-018100073Complex dispersions of poloxamers and mesoporous carriers with ibrutinibIgor A. Dain0Sergey A. Zolotov1Natalia B. Demina2Anna S. Zolotova3Grigorii A. Buzanov4Vasilii M. Retivov5Yevgenii S. Ponomaryov6Amedart LLC, Volgogradskiy pr. 42, bld. 24, Technopolis, Moscow 109316, Russia; Corresponding author.Amedart LLC, Volgogradskiy pr. 42, bld. 24, Technopolis, Moscow 109316, RussiaDepartment of Pharmaceutical Technology Institute of Pharmacy, Sechenov First Moscow State Medical University, Trubetskaya str., 8, bld. 2, Moscow 119991, RussiaAmedart LLC, Volgogradskiy pr. 42, bld. 24, Technopolis, Moscow 109316, RussiaKurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Leninskiy pr., 31, Moscow 119071, RussiaInstitute for Chemical Reagents and High Purity Chemical Substances of NRC “Kurchatov Institute”, Moscow, Bogorodskiy Val str., 3 107076, RussiaAmedart LLC, Volgogradskiy pr. 42, bld. 24, Technopolis, Moscow 109316, RussiaIbrutinib is an anticancer drug, a Bruton's tyrosine kinase inhibitor with poor solubility in aqueous media. This study reports on the study of the effectiveness of mesoporous carriers based on magnesium aluminometasilicate and poloxamers to improve the solubility and bioavailability of ibrutinib in the form of amorphous solid dispersions. The choice of the most effective composition was made on a parallel study of (a) a physical mixture of ibrutinib with a mesoporous carrier, (b) a solid dispersion with a poloxamer on a non-porous carrier, (c) a dispersion with a poloxamer deposited on a mesoporous carrier. Sample mixtures and dispersions with ibrutinib were tested to establish amorphism by various methods and to determine the solubility in aqueous media. The composition of ibrutinib-poloxamer P407-mesoporous carrier showed the best results in three standard media regarding the solubility of ibrutinib (increase in solubility at pH 1.2 - 129.6%, pH 4.5 - 300.2%, pH 6.8 - 363.3%). This composition became the basis for the tablet formulation and showed the best results in the Dissolution test (the dosage was dissolved in only 10 min of the test in pH 1.2 medium by 98.3%, pH 4.5 - 95.4%, pH 6.8 – 57.3%). These results were superior to those of the original Imbruvica capsules at all points in the study. In conclusion, the resulting formulation was stable under accelerated conditions according to the ICH Q1 Quality Guideline (40 °C, 75% relative humidity, 6 months).http://www.sciencedirect.com/science/article/pii/S2352952022000354IbrutinibMesoporous carrierDissolution testingX-ray powder diffractionPoloxamer |
| spellingShingle | Igor A. Dain Sergey A. Zolotov Natalia B. Demina Anna S. Zolotova Grigorii A. Buzanov Vasilii M. Retivov Yevgenii S. Ponomaryov Complex dispersions of poloxamers and mesoporous carriers with ibrutinib OpenNano Ibrutinib Mesoporous carrier Dissolution testing X-ray powder diffraction Poloxamer |
| title | Complex dispersions of poloxamers and mesoporous carriers with ibrutinib |
| title_full | Complex dispersions of poloxamers and mesoporous carriers with ibrutinib |
| title_fullStr | Complex dispersions of poloxamers and mesoporous carriers with ibrutinib |
| title_full_unstemmed | Complex dispersions of poloxamers and mesoporous carriers with ibrutinib |
| title_short | Complex dispersions of poloxamers and mesoporous carriers with ibrutinib |
| title_sort | complex dispersions of poloxamers and mesoporous carriers with ibrutinib |
| topic | Ibrutinib Mesoporous carrier Dissolution testing X-ray powder diffraction Poloxamer |
| url | http://www.sciencedirect.com/science/article/pii/S2352952022000354 |
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