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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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Autores principales: Lima, Ana Luiza, Pinho, Ludmila A. G., Chaker, Juliano A., Sa-Barreto, Livia L., Marreto, Ricardo Neves, Gratieri, Tais, Gelfuso, Guilherme M., Cunha-Filho, Marcilio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464369/
https://www.ncbi.nlm.nih.gov/pubmed/32824475
http://dx.doi.org/10.3390/pharmaceutics12080779
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author Lima, Ana Luiza
Pinho, Ludmila A. G.
Chaker, Juliano A.
Sa-Barreto, Livia L.
Marreto, Ricardo Neves
Gratieri, Tais
Gelfuso, Guilherme M.
Cunha-Filho, Marcilio
author_facet Lima, Ana Luiza
Pinho, Ludmila A. G.
Chaker, Juliano A.
Sa-Barreto, Livia L.
Marreto, Ricardo Neves
Gratieri, Tais
Gelfuso, Guilherme M.
Cunha-Filho, Marcilio
author_sort Lima, Ana Luiza
collection PubMed
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.
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spelling pubmed-74643692020-09-04 Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products Lima, Ana Luiza Pinho, Ludmila A. G. Chaker, Juliano A. Sa-Barreto, Livia L. Marreto, Ricardo Neves Gratieri, Tais Gelfuso, Guilherme M. Cunha-Filho, Marcilio Pharmaceutics Article 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. MDPI 2020-08-17 /pmc/articles/PMC7464369/ /pubmed/32824475 http://dx.doi.org/10.3390/pharmaceutics12080779 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lima, Ana Luiza
Pinho, Ludmila A. G.
Chaker, Juliano A.
Sa-Barreto, Livia L.
Marreto, Ricardo Neves
Gratieri, Tais
Gelfuso, Guilherme M.
Cunha-Filho, Marcilio
Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464369/
https://www.ncbi.nlm.nih.gov/pubmed/32824475
http://dx.doi.org/10.3390/pharmaceutics12080779
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