Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation
This study addressed the possibility of forming of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation metho...
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| Format: | Article |
| Language: | English |
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Sciendo
2015-06-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.1515/acph-2015-0014 |
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| author | Ali Ahmed Mahmoud Abdelhaleem Ali Adel Ahmed Maghrabi Ibrahim Abdullah |
| author_facet | Ali Ahmed Mahmoud Abdelhaleem Ali Adel Ahmed Maghrabi Ibrahim Abdullah |
| author_sort | Ali Ahmed Mahmoud Abdelhaleem |
| collection | DOAJ |
| description | This study addressed the possibility of forming of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1:1, 1:1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1:2) showed the highest dissolution percentage (> 95 % in 20 minutes) compared to pure crystalline CZ (56 %). Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1:1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with the great chance to bypass the first pass metabolism. |
| format | Article |
| id | doaj-art-0c4284ac41754cd9a2bcaaa19054b97e |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2015-06-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-0c4284ac41754cd9a2bcaaa19054b97e2025-02-02T19:57:23ZengSciendoActa Pharmaceutica1846-95582015-06-0165213314610.1515/acph-2015-0014acph-2015-0014Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluationAli Ahmed Mahmoud Abdelhaleem0Ali Adel Ahmed1Maghrabi Ibrahim Abdullah2Department of Pharmaceutics Faculty of Pharmacy Beni Suef University, EgyptDepartment of Pharmaceutics Faculty of Pharmacy Beni Suef University, EgyptDepartment of Clinical Pharmacy Faculty of Pharmacy Taif University Kingdom Saudi ArabiaThis study addressed the possibility of forming of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1:1, 1:1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1:2) showed the highest dissolution percentage (> 95 % in 20 minutes) compared to pure crystalline CZ (56 %). Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1:1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with the great chance to bypass the first pass metabolism.https://doi.org/10.1515/acph-2015-0014clozapinecarboxylic acidsco-amorphous systemsplasticizer |
| spellingShingle | Ali Ahmed Mahmoud Abdelhaleem Ali Adel Ahmed Maghrabi Ibrahim Abdullah Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation Acta Pharmaceutica clozapine carboxylic acids co-amorphous systems plasticizer |
| title | Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation |
| title_full | Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation |
| title_fullStr | Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation |
| title_full_unstemmed | Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation |
| title_short | Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation |
| title_sort | clozapine carboxylic acid plasticized co amorphous dispersions preparation characterization and solution stability evaluation |
| topic | clozapine carboxylic acids co-amorphous systems plasticizer |
| url | https://doi.org/10.1515/acph-2015-0014 |
| work_keys_str_mv | AT aliahmedmahmoudabdelhaleem clozapinecarboxylicacidplasticizedcoamorphousdispersionspreparationcharacterizationandsolutionstabilityevaluation AT aliadelahmed clozapinecarboxylicacidplasticizedcoamorphousdispersionspreparationcharacterizationandsolutionstabilityevaluation AT maghrabiibrahimabdullah clozapinecarboxylicacidplasticizedcoamorphousdispersionspreparationcharacterizationandsolutionstabilityevaluation |