Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation
Sirolimus, a potent immunosuppressant, has been demonstrated to have remarkable activity in inhibiting allograft rejection in transplantation. The objective of the study was to fabricate microsponge mini tablets with enhanced solubility and bioavailability. β-Cyclodextrin and NEOCEL C91 were selecte...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423002943 |
| _version_ | 1797632677443010560 |
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| author | Yasir Mehmood Hira Shahid Muhammad Abbas Umar Farooq Shaukat Ali Mohsin Kazi |
| author_facet | Yasir Mehmood Hira Shahid Muhammad Abbas Umar Farooq Shaukat Ali Mohsin Kazi |
| author_sort | Yasir Mehmood |
| collection | DOAJ |
| description | Sirolimus, a potent immunosuppressant, has been demonstrated to have remarkable activity in inhibiting allograft rejection in transplantation. The objective of the study was to fabricate microsponge mini tablets with enhanced solubility and bioavailability. β-Cyclodextrin and NEOCEL C91 were selected to prepare the microsponges (SLM-M) to improve the stability and solubility of sirolimus. The current study involved the quasi emulsion-solvent diffusion technique to design sirolimus-loaded microsponges that were further compressed into mini tablets 4 mm in diameter. Solid-state characterization, dissolution at different pH values, stability, and pharmacokinetic profiles with IVIVC data were analyzed in humans. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to characterize the formulations, and high-performance liquid chromatography (HPLC) was used to assess the drug stability of the compressed microsponge minitablets. The API changed from the crystalline state to an amorphous state, as shown by XRD and DSC. The compressed mini tablets showed a 4-fold enhancement in the drug dissolution profile. A toxicology investigation suggested that mini tablets were safe. In humans, the bioavailability of sirolimus compressed mini tablets from SLM-M was significantly improved. The results suggest that mini tablets prepared with β-cyclodextrin and NEOCEL C91 by a quasi emulsion-solvent diffusion process might be an alternative way to improve the bioavailability of sirolimus. In addition, the manufacturing process is easily scalable for the commercialization of drugs to market. |
| first_indexed | 2024-03-11T11:41:13Z |
| format | Article |
| id | doaj.art-1d267b534aeb4a4aae11da4d283063cb |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-11T11:41:13Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-1d267b534aeb4a4aae11da4d283063cb2023-11-10T04:16:02ZengElsevierSaudi Pharmaceutical Journal1319-01642023-11-013111101799Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlationYasir Mehmood0Hira Shahid1Muhammad Abbas2Umar Farooq3Shaukat Ali4Mohsin Kazi5Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University, Faisalabad, P. O. Box 38000, Pakistan; Corresponding authors.Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, P.O. Box 38000, PakistanImran Idress College of Pharmacy, Sialkot P.O. Box 51310, PakistanFaculty of Pharmacy, Grand Asian University, Sialkot, Punjab P.O. Box 51310, PakistanAscendia Pharma, Inc. North Brunswick, NJ 08902 USADepartment of Pharmaceutics, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi Arabia; Corresponding authors.Sirolimus, a potent immunosuppressant, has been demonstrated to have remarkable activity in inhibiting allograft rejection in transplantation. The objective of the study was to fabricate microsponge mini tablets with enhanced solubility and bioavailability. β-Cyclodextrin and NEOCEL C91 were selected to prepare the microsponges (SLM-M) to improve the stability and solubility of sirolimus. The current study involved the quasi emulsion-solvent diffusion technique to design sirolimus-loaded microsponges that were further compressed into mini tablets 4 mm in diameter. Solid-state characterization, dissolution at different pH values, stability, and pharmacokinetic profiles with IVIVC data were analyzed in humans. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to characterize the formulations, and high-performance liquid chromatography (HPLC) was used to assess the drug stability of the compressed microsponge minitablets. The API changed from the crystalline state to an amorphous state, as shown by XRD and DSC. The compressed mini tablets showed a 4-fold enhancement in the drug dissolution profile. A toxicology investigation suggested that mini tablets were safe. In humans, the bioavailability of sirolimus compressed mini tablets from SLM-M was significantly improved. The results suggest that mini tablets prepared with β-cyclodextrin and NEOCEL C91 by a quasi emulsion-solvent diffusion process might be an alternative way to improve the bioavailability of sirolimus. In addition, the manufacturing process is easily scalable for the commercialization of drugs to market.http://www.sciencedirect.com/science/article/pii/S1319016423002943SirolimusSolubilitySolid dispersionsBioavailabilityIVIVC |
| spellingShingle | Yasir Mehmood Hira Shahid Muhammad Abbas Umar Farooq Shaukat Ali Mohsin Kazi Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation Saudi Pharmaceutical Journal Sirolimus Solubility Solid dispersions Bioavailability IVIVC |
| title | Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation |
| title_full | Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation |
| title_fullStr | Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation |
| title_full_unstemmed | Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation |
| title_short | Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation |
| title_sort | microsponge derived mini tablets loaded with immunosuppressive agents pharmacokinetic investigation in human volunteers cell viability and ivivc correlation |
| topic | Sirolimus Solubility Solid dispersions Bioavailability IVIVC |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423002943 |
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