Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability
This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12215 |
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| author | Vladimir B. Markeev Evgenia V. Blynskaya Sergey V. Tishkov Konstantin V. Alekseev Anna I. Marakhova Alexandre A. Vetcher Alexander Y. Shishonin |
| author_facet | Vladimir B. Markeev Evgenia V. Blynskaya Sergey V. Tishkov Konstantin V. Alekseev Anna I. Marakhova Alexandre A. Vetcher Alexander Y. Shishonin |
| author_sort | Vladimir B. Markeev |
| collection | DOAJ |
| description | This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus<sup>®</sup> was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus<sup>®</sup>, which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution. |
| first_indexed | 2024-03-11T00:25:08Z |
| format | Article |
| id | doaj.art-24341e95a2cc4daaa121f935923d8c8f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:25:08Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-24341e95a2cc4daaa121f935923d8c8f2023-11-18T23:01:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151221510.3390/ijms241512215Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and StabilityVladimir B. Markeev0Evgenia V. Blynskaya1Sergey V. Tishkov2Konstantin V. Alekseev3Anna I. Marakhova4Alexandre A. Vetcher5Alexander Y. Shishonin6V.V. Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., 125315 Moscow, RussiaV.V. Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., 125315 Moscow, RussiaV.V. Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., 125315 Moscow, RussiaV.V. Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., 125315 Moscow, RussiaInstitute of Biochemical Technology and Nanotechnology, Peoples’ Friendship University of Russia n.a. P. Lumumba (RUDN), 6 Miklukho-Maklaya St., 117198 Moscow, RussiaInstitute of Biochemical Technology and Nanotechnology, Peoples’ Friendship University of Russia n.a. P. Lumumba (RUDN), 6 Miklukho-Maklaya St., 117198 Moscow, RussiaComplementary and Integrative Health Clinic of Dr. Shishonin, 5, Yasnogorskaya St., 117588 Moscow, RussiaThis work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus<sup>®</sup> was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus<sup>®</sup>, which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution.https://www.mdpi.com/1422-0067/24/15/12215amorphous solid dispersionscompositesolubilitybioavailabilityanxiolyticsantidepressants |
| spellingShingle | Vladimir B. Markeev Evgenia V. Blynskaya Sergey V. Tishkov Konstantin V. Alekseev Anna I. Marakhova Alexandre A. Vetcher Alexander Y. Shishonin Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability International Journal of Molecular Sciences amorphous solid dispersions composite solubility bioavailability anxiolytics antidepressants |
| title | Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability |
| title_full | Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability |
| title_fullStr | Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability |
| title_full_unstemmed | Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability |
| title_short | Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability |
| title_sort | composites of n butyl n methyl 1 phenylpyrrolo 1 2 a pyrazine 3 carboxamide with polymers effect of crystallinity on solubility and stability |
| topic | amorphous solid dispersions composite solubility bioavailability anxiolytics antidepressants |
| url | https://www.mdpi.com/1422-0067/24/15/12215 |
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