Co-crystallization for enhanced dissolution rate of bicalutamide: preparation and evaluation of rapidly disintegrating tablets
| Autor: | Aya R Elbasuony, Gamal M. El Maghraby, Ebtessam A. Essa, Abdelaziz E. Abdelaziz |
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| Rok vydání: | 2019 |
| Předmět: |
Sucrose
Sucralose Bicalutamide Chemistry Pharmaceutical Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy law.invention Excipients Tosyl Compounds 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine X-Ray Diffraction law Nitriles Spectroscopy Fourier Transform Infrared Drug Discovery medicine Acetone Anilides Crystallization Fourier transform infrared spectroscopy Dissolution Pharmacology Calorimetry Differential Scanning Organic Chemistry 021001 nanoscience & nanotechnology Bioavailability Solvent Solubility chemistry 0210 nano-technology Tablets Nuclear chemistry medicine.drug |
| Zdroj: | Drug Development and Industrial Pharmacy. 45:1215-1223 |
| ISSN: | 1520-5762 0363-9045 |
| DOI: | 10.1080/03639045.2019.1571504 |
| Popis: | Objectives: Enhance the dissolution rate of bicalutamide via co-crystallization with sucralose (sweetener), with the aim to develop rapidly disintegrating tablets with subsequent prompt dissolution. Significance: Bicalutamide is antiandrogenic agent for the treatment of prostate cancer but has low and variable oral bioavailability, mainly attributed to poor dissolution. Co-crystallization with benign excipients is promising for dissolution enhancement with the additive serving dual functions. The benefit will become greater if dissolution enhancement is associated with the development of orodispersible tablets which is suitable for elderly patients who are the most vulnerable for prostate cancer. Methods: Bicalutamide was dissolved in acetone in the presence of increasing molar ratios of sucralose. The solvent was evaporated while mixing to deposit crystals that were subjected to wet co-grinding until drying. The developed solids were characterized using Fourier transform infrared spectroscopy, differential thermal analysis and X-ray diffraction in addition to monitoring bicalutamide dissolution. Results: Instrumental analysis provided evidences for co-crystallization which was initiated at 1:1 molar ratio of bicalutamide to sucralose with complete co-crystallization at 1:4 molar ratio. The co-crystals provided faster bicalutamide dissolution compared with the unprocessed drug and that recrystalized from acetone in the absence of sucralose. The formulation containing bicalutamide with sucralose at 1:4 molar ratio was selected for tablet formulation into which superdisintegrants were included. The developed tablets exhibited flash disintegration with subsequent fast dissolution of bicalutamide. Conclusions: The study introduced co-crystallization of bicalutamide with sucralose as an efficient tool to enhance the dissolution rate and to develop rapidly dissolving tablets for intraoral administration. |
| Databáze: | OpenAIRE |
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