Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir
Amorphous salt solid dispersion (ASSD) of Dolutegravir amorphous salt (DSSD) was generated using quench cooling and compared to its Dolutegravir free acid solid dispersion (DFSD) to improve the solubility and bioavailability. Soluplus (SLP) was used as a polymeric carrier in both solid dispersions....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Advances in Pharmacological and Pharmaceutical Sciences |
| Online Access: | http://dx.doi.org/10.1155/2023/7198674 |
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| author | Dani Lakshman Yarlagadda Akshatha M. Nayak Bheemisetty Brahmam Krishnamurthy Bhat |
| author_facet | Dani Lakshman Yarlagadda Akshatha M. Nayak Bheemisetty Brahmam Krishnamurthy Bhat |
| author_sort | Dani Lakshman Yarlagadda |
| collection | DOAJ |
| description | Amorphous salt solid dispersion (ASSD) of Dolutegravir amorphous salt (DSSD) was generated using quench cooling and compared to its Dolutegravir free acid solid dispersion (DFSD) to improve the solubility and bioavailability. Soluplus (SLP) was used as a polymeric carrier in both solid dispersions. The prepared DSSD and DFSD, physical mixtures, and individual compounds were characterized by employing DSC, XRPD, and FTIR to assess the formation of the single homogenous amorphous phase and the existence of intermolecular interactions. Partial crystallinity was observed for DSSD, unlike DFSD, which is completely amorphous. No intermolecular interactions were observed between the Dolutegravir sodium (DS)/Dolutegravir free acid (DF) and SLP from the FTIR spectra of DSSD and DFSD. Both DSSD and DFSD improved the solubility of Dolutegravir (DTG) to 5.7 and 4.54 folds compared to the pure forms. Similarly, drug release from DSSD and DFSD was 2 and 1.5 folds higher than that in the pure form, owing to the rapid dissolution of the drug from the formulations. The permeability of DSSD and DFSD was estimated using the dialysis membrane, which enhanced the DTG permeability. The improvement in in vitro studies was translated into in vivo pharmacokinetic profiles of DSSD and DFSD, where 4.0 and 5.6 folds, respectively, improved the Cmax of DTG. |
| first_indexed | 2024-03-13T02:57:37Z |
| format | Article |
| id | doaj.art-700932ea788149498abddea0c9d64aaa |
| institution | Directory Open Access Journal |
| issn | 2633-4690 |
| language | English |
| last_indexed | 2024-03-13T02:57:37Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Advances in Pharmacological and Pharmaceutical Sciences |
| spelling | doaj.art-700932ea788149498abddea0c9d64aaa2023-06-28T00:00:33ZengHindawi LimitedAdvances in Pharmacological and Pharmaceutical Sciences2633-46902023-01-01202310.1155/2023/7198674Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of DolutegravirDani Lakshman Yarlagadda0Akshatha M. Nayak1Bheemisetty Brahmam2Krishnamurthy Bhat3Department of Pharmaceutical Quality AssuranceDepartment of Pharmaceutical Quality AssuranceDepartment of PharmaceuticsDepartment of Pharmaceutical Quality AssuranceAmorphous salt solid dispersion (ASSD) of Dolutegravir amorphous salt (DSSD) was generated using quench cooling and compared to its Dolutegravir free acid solid dispersion (DFSD) to improve the solubility and bioavailability. Soluplus (SLP) was used as a polymeric carrier in both solid dispersions. The prepared DSSD and DFSD, physical mixtures, and individual compounds were characterized by employing DSC, XRPD, and FTIR to assess the formation of the single homogenous amorphous phase and the existence of intermolecular interactions. Partial crystallinity was observed for DSSD, unlike DFSD, which is completely amorphous. No intermolecular interactions were observed between the Dolutegravir sodium (DS)/Dolutegravir free acid (DF) and SLP from the FTIR spectra of DSSD and DFSD. Both DSSD and DFSD improved the solubility of Dolutegravir (DTG) to 5.7 and 4.54 folds compared to the pure forms. Similarly, drug release from DSSD and DFSD was 2 and 1.5 folds higher than that in the pure form, owing to the rapid dissolution of the drug from the formulations. The permeability of DSSD and DFSD was estimated using the dialysis membrane, which enhanced the DTG permeability. The improvement in in vitro studies was translated into in vivo pharmacokinetic profiles of DSSD and DFSD, where 4.0 and 5.6 folds, respectively, improved the Cmax of DTG.http://dx.doi.org/10.1155/2023/7198674 |
| spellingShingle | Dani Lakshman Yarlagadda Akshatha M. Nayak Bheemisetty Brahmam Krishnamurthy Bhat Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir Advances in Pharmacological and Pharmaceutical Sciences |
| title | Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir |
| title_full | Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir |
| title_fullStr | Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir |
| title_full_unstemmed | Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir |
| title_short | Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir |
| title_sort | exploring the solubility and bioavailability of sodium salt and its free acid solid dispersions of dolutegravir |
| url | http://dx.doi.org/10.1155/2023/7198674 |
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