Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers
| Autor: | Dea Herrera-Ruiz, Patricia Rodríguez-Cuamatzi, Herbert Höpfl, Obdulia Sánchez-Guadarrama, Reynaldo Salas-Zúñiga, Christian Rodríguez-Ruiz, Hugo Morales-Rojas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
multicomponent crystals
crystallization inhibitors Pharmaceutical Science Excipient lcsh:RS1-441 chemical and pharmacologic phenomena 02 engineering and technology 030226 pharmacology & pharmacy Dosage form Article lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine stomatognathic system parasitic diseases nitazoxanide medicine Solubility cocrystals Dissolution dissolution behavior chemistry.chemical_classification Supersaturation Chemistry drug-polymer interactions technology industry and agriculture Polymer supersaturated formulations 021001 nanoscience & nanotechnology Phosphate Bioavailability carbohydrates (lipids) body regions 0210 nano-technology medicine.drug Nuclear chemistry |
| Zdroj: | Pharmaceutics, Vol 12, Iss 1, p 23 (2019) Pharmaceutics Volume 12 Issue 1 |
| ISSN: | 1999-4923 |
| Popis: | The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel® 60 HG) on the dissolution behavior of two cocrystals derived from nitazoxanide (NTZ), viz., nitazoxanide-glutaric acid (NTZ-GLU, 1:1) and nitazoxanide-succinic acid (NTZ-SUC, 2:1), was explored. Powder dissolution experiments under non-sink conditions showed similar dissolution profiles for the cocrystals and pure NTZ. However, pre-dissolved cellulosic polymer in the phosphate dissolution medium (pH 7.5) modified the dissolution profile of NTZ when starting from the cocrystals, achieving transient drug supersaturation. Subsequent dissolution studies under sink conditions of polymer-based pharmaceutical powder formulations with NTZ-SUC cocrystals gave a significant improvement of the apparent solubility of NTZ when compared with analogous formulations of pure NTZ and the physical mixture of NTZ and SUC. Scanning electron microscopy and powder X-ray diffraction analysis of samples recovered after the powder dissolution studies showed that the cocrystals undergo fast dissolution, drug supersaturation and precipitation both in the absence and presence of polymer, suggesting that the solubilization enhancement is due to polymer-induced delay of nucleation and crystal growth of the less soluble NTZ form. The study demonstrates that the incorporation of an appropriate excipient in adequate concentration can be a key factor for inducing and maintaining the solubilization of poorly soluble drugs starting from co-crystallized solid forms. In such a way, cocrystals can be suitable for the development of solid dosage forms with improved bioavailability and efficacy in the treatment of important parasitic and viral diseases, among others. |
| Databáze: | OpenAIRE |
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