Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products
Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/8/779 |
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| author | Ana Luiza Lima Ludmila A. G. Pinho Juliano A. Chaker Livia L. Sa-Barreto Ricardo Neves Marreto Tais Gratieri Guilherme M. Gelfuso Marcilio Cunha-Filho |
| author_facet | Ana Luiza Lima Ludmila A. G. Pinho Juliano A. Chaker Livia L. Sa-Barreto Ricardo Neves Marreto Tais Gratieri Guilherme M. Gelfuso Marcilio Cunha-Filho |
| author_sort | Ana Luiza Lima |
| collection | DOAJ |
| description | Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15–20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability. |
| first_indexed | 2024-03-10T17:19:15Z |
| format | Article |
| id | doaj.art-699d9121ae494fd79ab32a9464cddc06 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T17:19:15Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-699d9121ae494fd79ab32a9464cddc062023-11-20T10:23:11ZengMDPI AGPharmaceutics1999-49232020-08-0112877910.3390/pharmaceutics12080779Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug ProductsAna Luiza Lima0Ludmila A. G. Pinho1Juliano A. Chaker2Livia L. Sa-Barreto3Ricardo Neves Marreto4Tais Gratieri5Guilherme M. Gelfuso6Marcilio Cunha-Filho7Laboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, University of Brasilia, Brasília 70910-900, BrazilLaboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, University of Brasilia, Brasília 70910-900, BrazilFaculty of Ceilândia, University of Brasília (UnB), Brasília 72220-900, BrazilFaculty of Ceilândia, University of Brasília (UnB), Brasília 72220-900, BrazilLaboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy, Federal University of Goiás, Goiânia 74690-900, BrazilLaboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, University of Brasilia, Brasília 70910-900, BrazilLaboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, University of Brasilia, Brasília 70910-900, BrazilLaboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, University of Brasilia, Brasília 70910-900, BrazilHere, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15–20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability.https://www.mdpi.com/1999-4923/12/8/779hot-melt extrusioneffervescent drug productstabilityhygroscopicitydisintegration time |
| spellingShingle | Ana Luiza Lima Ludmila A. G. Pinho Juliano A. Chaker Livia L. Sa-Barreto Ricardo Neves Marreto Tais Gratieri Guilherme M. Gelfuso Marcilio Cunha-Filho Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products Pharmaceutics hot-melt extrusion effervescent drug product stability hygroscopicity disintegration time |
| title | Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products |
| title_full | Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products |
| title_fullStr | Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products |
| title_full_unstemmed | Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products |
| title_short | Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products |
| title_sort | hot melt extrusion as an advantageous technology to obtain effervescent drug products |
| topic | hot-melt extrusion effervescent drug product stability hygroscopicity disintegration time |
| url | https://www.mdpi.com/1999-4923/12/8/779 |
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