Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics
The present study focuses on the synthesis of the natural product 4-methyl-umbelliferone (4-MU, hymecromone), the preparation, characterization, and biological activity evaluation of 4-MU inclusion complexes with <i>β</i>-cyclodextrin (<i>β</i>-CD), as well as their incorpora...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Micro |
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| Online Access: | https://www.mdpi.com/2673-8023/3/4/61 |
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| author | Eleni Kavetsou Ioanna Pitterou Nikos G. Dimitrioglou Stefanos Kikionis Eftichia Kritsi Panagiotis Zoumpoulakis Eleni Pontiki Dimitra Hadjipavlou-Litina Dimitris T. Hatziavramidis Anastasia Detsi |
| author_facet | Eleni Kavetsou Ioanna Pitterou Nikos G. Dimitrioglou Stefanos Kikionis Eftichia Kritsi Panagiotis Zoumpoulakis Eleni Pontiki Dimitra Hadjipavlou-Litina Dimitris T. Hatziavramidis Anastasia Detsi |
| author_sort | Eleni Kavetsou |
| collection | DOAJ |
| description | The present study focuses on the synthesis of the natural product 4-methyl-umbelliferone (4-MU, hymecromone), the preparation, characterization, and biological activity evaluation of 4-MU inclusion complexes with <i>β</i>-cyclodextrin (<i>β</i>-CD), as well as their incorporation into pharmaceutical tablets. The inclusion complexes (ICs) were characterized using DLS, SEM, TGA as well as FT-IR, UV-vis, and NMR spectroscopies. The release profile of 4-MU from the <i>β</i>-CD-4-MU ICs was studied in three different pH: 1.2 (aqueous hydrochloric acid), 7.4, and 6.8 (phosphate-buffered solutions), to simulate the stomach, physiological, and intestine pH, respectively. The ICs were incorporated in pharmaceutical tablets which were prepared by direct compression and were characterized for their mechanical properties. The optimal composition of 4-MU as the active pharmaceutical ingredient (API) and excipients was determined using design of experiment (DoE), and the dissolution studies were performed at pH 1.2 at 37 ± 0.5 °C. The sustained release profile of the pharmaceutical tablets showed a delayed burst release effect at 20 min (20% drug release) compared to that of the ICs at the same time interval (70%). The results indicated that the kinetic model describing the release profile of 4-MU from the ICs and tablets is the Higuchi model, while the release mechanism is swelling and diffusion, as was indicated by the Korsmeyer–Peppas kinetic model. The optimization analysis revealed that the optimum composition contains <i>x</i><sub>1</sub> = 150.95 mg of <i>β</i>-CD-4-MU ICs, <i>x</i><sub>2</sub> = 82.65 mg of microcrystalline cellulose, and <i>x</i><sub>3</sub> = 12.40 mg of calcium phosphate. |
| first_indexed | 2024-03-08T20:31:40Z |
| format | Article |
| id | doaj.art-24e01ac5a7c44881b2c7c4cc1b831181 |
| institution | Directory Open Access Journal |
| issn | 2673-8023 |
| language | English |
| last_indexed | 2024-03-08T20:31:40Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micro |
| spelling | doaj.art-24e01ac5a7c44881b2c7c4cc1b8311812023-12-22T14:25:01ZengMDPI AGMicro2673-80232023-11-013489291110.3390/micro3040061Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution KineticsEleni Kavetsou0Ioanna Pitterou1Nikos G. Dimitrioglou2Stefanos Kikionis3Eftichia Kritsi4Panagiotis Zoumpoulakis5Eleni Pontiki6Dimitra Hadjipavlou-Litina7Dimitris T. Hatziavramidis8Anastasia Detsi9Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, GR-15780 Athens, GreeceLaboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, GR-15780 Athens, GreeceLaboratory of Organic Chemical Technology, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, GR-15772 Athens, GreeceSection of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, GR-15771 Athens, GreeceLaboratory of Chemistry, Analysis & Design of Food Processes, Department of Food Science and Technology, University of West Attica, GR-12243 Egaleo, GreeceLaboratory of Chemistry, Analysis & Design of Food Processes, Department of Food Science and Technology, University of West Attica, GR-12243 Egaleo, GreeceLaboratory of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, GreeceLaboratory of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, GreeceLaboratory of Organic Chemical Technology, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, GR-15772 Athens, GreeceLaboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, GR-15780 Athens, GreeceThe present study focuses on the synthesis of the natural product 4-methyl-umbelliferone (4-MU, hymecromone), the preparation, characterization, and biological activity evaluation of 4-MU inclusion complexes with <i>β</i>-cyclodextrin (<i>β</i>-CD), as well as their incorporation into pharmaceutical tablets. The inclusion complexes (ICs) were characterized using DLS, SEM, TGA as well as FT-IR, UV-vis, and NMR spectroscopies. The release profile of 4-MU from the <i>β</i>-CD-4-MU ICs was studied in three different pH: 1.2 (aqueous hydrochloric acid), 7.4, and 6.8 (phosphate-buffered solutions), to simulate the stomach, physiological, and intestine pH, respectively. The ICs were incorporated in pharmaceutical tablets which were prepared by direct compression and were characterized for their mechanical properties. The optimal composition of 4-MU as the active pharmaceutical ingredient (API) and excipients was determined using design of experiment (DoE), and the dissolution studies were performed at pH 1.2 at 37 ± 0.5 °C. The sustained release profile of the pharmaceutical tablets showed a delayed burst release effect at 20 min (20% drug release) compared to that of the ICs at the same time interval (70%). The results indicated that the kinetic model describing the release profile of 4-MU from the ICs and tablets is the Higuchi model, while the release mechanism is swelling and diffusion, as was indicated by the Korsmeyer–Peppas kinetic model. The optimization analysis revealed that the optimum composition contains <i>x</i><sub>1</sub> = 150.95 mg of <i>β</i>-CD-4-MU ICs, <i>x</i><sub>2</sub> = 82.65 mg of microcrystalline cellulose, and <i>x</i><sub>3</sub> = 12.40 mg of calcium phosphate.https://www.mdpi.com/2673-8023/3/4/614-methyl-umbelliferone<i>β</i>-cyclodextrinexcipientsformulationpharmaceutical tabletsrelease profile |
| spellingShingle | Eleni Kavetsou Ioanna Pitterou Nikos G. Dimitrioglou Stefanos Kikionis Eftichia Kritsi Panagiotis Zoumpoulakis Eleni Pontiki Dimitra Hadjipavlou-Litina Dimitris T. Hatziavramidis Anastasia Detsi Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics Micro 4-methyl-umbelliferone <i>β</i>-cyclodextrin excipients formulation pharmaceutical tablets release profile |
| title | Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics |
| title_full | Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics |
| title_fullStr | Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics |
| title_full_unstemmed | Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics |
| title_short | Formulation of Pharmaceutical Tablets Containing <i>β</i>-Cyclodextrin-4-Methyl-Umbelliferone (Hymecromone) Inclusion Complexes and Study of the Dissolution Kinetics |
| title_sort | formulation of pharmaceutical tablets containing i β i cyclodextrin 4 methyl umbelliferone hymecromone inclusion complexes and study of the dissolution kinetics |
| topic | 4-methyl-umbelliferone <i>β</i>-cyclodextrin excipients formulation pharmaceutical tablets release profile |
| url | https://www.mdpi.com/2673-8023/3/4/61 |
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