Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers
The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel<sup>®</sup> 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 e...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/1/23 |
| _version_ | 1811304290532196352 |
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| author | Reynaldo Salas-Zúñiga Christian Rodríguez-Ruiz Herbert Höpfl Hugo Morales-Rojas Obdulia Sánchez-Guadarrama Patricia Rodríguez-Cuamatzi Dea Herrera-Ruiz |
| author_facet | Reynaldo Salas-Zúñiga Christian Rodríguez-Ruiz Herbert Höpfl Hugo Morales-Rojas Obdulia Sánchez-Guadarrama Patricia Rodríguez-Cuamatzi Dea Herrera-Ruiz |
| author_sort | Reynaldo Salas-Zúñiga |
| collection | DOAJ |
| description | The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel<sup>®</sup> 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. |
| first_indexed | 2024-04-13T08:04:41Z |
| format | Article |
| id | doaj.art-57acad446a9240f28978e76bd803acad |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T08:04:41Z |
| publishDate | 2019-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-57acad446a9240f28978e76bd803acad2022-12-22T02:55:12ZengMDPI AGPharmaceutics1999-49232019-12-011212310.3390/pharmaceutics12010023pharmaceutics12010023Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic PolymersReynaldo Salas-Zúñiga0Christian Rodríguez-Ruiz1Herbert Höpfl2Hugo Morales-Rojas3Obdulia Sánchez-Guadarrama4Patricia Rodríguez-Cuamatzi5Dea Herrera-Ruiz6Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, MexicoCentro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, MexicoCentro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, MexicoCentro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, MexicoDepartamento de Ingeniería Química, Universidad Politécnica de Tlaxcala, Carretera Federal Tlaxcala-Puebla Km 9.5, Tepeyanco, Tlaxcala 90180, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, MexicoThe effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel<sup>®</sup> 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.https://www.mdpi.com/1999-4923/12/1/23nitazoxanidecocrystalsmulticomponent crystalsdissolution behaviorsupersaturated formulationscrystallization inhibitorsdrug-polymer interactions |
| spellingShingle | Reynaldo Salas-Zúñiga Christian Rodríguez-Ruiz Herbert Höpfl Hugo Morales-Rojas Obdulia Sánchez-Guadarrama Patricia Rodríguez-Cuamatzi Dea Herrera-Ruiz Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers Pharmaceutics nitazoxanide cocrystals multicomponent crystals dissolution behavior supersaturated formulations crystallization inhibitors drug-polymer interactions |
| title | Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers |
| title_full | Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers |
| title_fullStr | Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers |
| title_full_unstemmed | Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers |
| title_short | Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers |
| title_sort | dissolution advantage of nitazoxanide cocrystals in the presence of cellulosic polymers |
| topic | nitazoxanide cocrystals multicomponent crystals dissolution behavior supersaturated formulations crystallization inhibitors drug-polymer interactions |
| url | https://www.mdpi.com/1999-4923/12/1/23 |
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