Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies
Risperidone (RSP) is an atypical antipsychotic drug which acts as a potent antagonist of serotonin-2 (5TH2) and dopamine-2 (D2) receptors in the brain; it is used to treat schizophrenia, behavioral and psychological symptoms of dementia and irritability associated with autism. It is a poorly water s...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/23/5694 |
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| author | Laura Sbârcea Ionuț-Mihai Tănase Adriana Ledeți Denisa Cîrcioban Gabriela Vlase Paul Barvinschi Marinela Miclău Renata-Maria Văruţ Cristina Trandafirescu Ionuț Ledeți |
| author_facet | Laura Sbârcea Ionuț-Mihai Tănase Adriana Ledeți Denisa Cîrcioban Gabriela Vlase Paul Barvinschi Marinela Miclău Renata-Maria Văruţ Cristina Trandafirescu Ionuț Ledeți |
| author_sort | Laura Sbârcea |
| collection | DOAJ |
| description | Risperidone (RSP) is an atypical antipsychotic drug which acts as a potent antagonist of serotonin-2 (5TH2) and dopamine-2 (D2) receptors in the brain; it is used to treat schizophrenia, behavioral and psychological symptoms of dementia and irritability associated with autism. It is a poorly water soluble benzoxazole derivative with high lipophilicity. Supramolecular adducts between drug substance and two methylated β-cyclodextrins, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) were obtained in order to enhance RSP solubility and improve its biopharmaceutical profile. The inclusion complexes were evaluated by means of thermoanalytical methods (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow), powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy and saturation solubility studies. Job’s method was employed for the determination of the stoichiometry of the inclusion complexes, which was found to be 2:1 for both guest–host systems. Molecular modeling studies were carried out for an in-depth characterization of the interaction between drug substance and cyclodextrins (CDs). The physicochemical properties of the supramolecular systems differ from those of RSP, demonstrating the inclusion complex formation between drug and CDs. The RSP solubility was enhanced as a result of drug encapsulation in the CDs cavity, the higher increase being obtained with DM-β-CD as host; the guest–host system RSP/DM-β-CD can thus be a starting point for further research in developing new formulations containing RSP, with enhanced bioavailability. |
| first_indexed | 2024-03-10T14:22:24Z |
| format | Article |
| id | doaj.art-778f75f559ac4409ae2a45f968265497 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:22:24Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-778f75f559ac4409ae2a45f9682654972023-11-20T23:18:41ZengMDPI AGMolecules1420-30492020-12-012523569410.3390/molecules25235694Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling StudiesLaura Sbârcea0Ionuț-Mihai Tănase1Adriana Ledeți2Denisa Cîrcioban3Gabriela Vlase4Paul Barvinschi5Marinela Miclău6Renata-Maria Văruţ7Cristina Trandafirescu8Ionuț Ledeți9Department of Pharmacy I, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, RomaniaFaculty of Industrial Chemistry and Environmental Engineering, Politehnica University of Timisoara, 6 Vasile Parvan Blvd, 300223 Timisoara, RomaniaDepartment of Pharmacy I, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, RomaniaDepartment of Pharmacy I, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, RomaniaResearch Centre for Thermal Analysis in Environmental Problems, West University of Timisoara, 16 Pestalozzi Street, 300115 Timisoara, RomaniaFaculty of Physics, West University of Timisoara, 4 Vasile Parvan Blvd, 300223 Timisoara, RomaniaNational Institute for Research and Development in Electrochemistry and Condensed Matter, 144 Dr. A. Păunescu-Podeanu Street, 300587 Timisoara, RomaniaFaculty of Pharmacy, University of Medicine and Pharmacy Craiova, 2–4 Petru Rares Street, 200349 Craiova, RomaniaDepartment of Pharmacy II, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, RomaniaDepartment of Pharmacy I, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, RomaniaRisperidone (RSP) is an atypical antipsychotic drug which acts as a potent antagonist of serotonin-2 (5TH2) and dopamine-2 (D2) receptors in the brain; it is used to treat schizophrenia, behavioral and psychological symptoms of dementia and irritability associated with autism. It is a poorly water soluble benzoxazole derivative with high lipophilicity. Supramolecular adducts between drug substance and two methylated β-cyclodextrins, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) were obtained in order to enhance RSP solubility and improve its biopharmaceutical profile. The inclusion complexes were evaluated by means of thermoanalytical methods (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow), powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy and saturation solubility studies. Job’s method was employed for the determination of the stoichiometry of the inclusion complexes, which was found to be 2:1 for both guest–host systems. Molecular modeling studies were carried out for an in-depth characterization of the interaction between drug substance and cyclodextrins (CDs). The physicochemical properties of the supramolecular systems differ from those of RSP, demonstrating the inclusion complex formation between drug and CDs. The RSP solubility was enhanced as a result of drug encapsulation in the CDs cavity, the higher increase being obtained with DM-β-CD as host; the guest–host system RSP/DM-β-CD can thus be a starting point for further research in developing new formulations containing RSP, with enhanced bioavailability.https://www.mdpi.com/1420-3049/25/23/5694risperidonecyclodextrinsmolecular encapsulationinclusion complexsolubility |
| spellingShingle | Laura Sbârcea Ionuț-Mihai Tănase Adriana Ledeți Denisa Cîrcioban Gabriela Vlase Paul Barvinschi Marinela Miclău Renata-Maria Văruţ Cristina Trandafirescu Ionuț Ledeți Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies Molecules risperidone cyclodextrins molecular encapsulation inclusion complex solubility |
| title | Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies |
| title_full | Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies |
| title_fullStr | Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies |
| title_full_unstemmed | Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies |
| title_short | Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies |
| title_sort | encapsulation of risperidone by methylated β cyclodextrins physicochemical and molecular modeling studies |
| topic | risperidone cyclodextrins molecular encapsulation inclusion complex solubility |
| url | https://www.mdpi.com/1420-3049/25/23/5694 |
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