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Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate
Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milli...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9610000/ https://www.ncbi.nlm.nih.gov/pubmed/36297608 http://dx.doi.org/10.3390/pharmaceutics14102173 |
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author | Patera, Jan Němečková, Pavla Zámostný, Petr |
author_facet | Patera, Jan Němečková, Pavla Zámostný, Petr |
author_sort | Patera, Jan |
collection | PubMed |
description | Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5–25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion—surface utilization factor—were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing. |
format | Online Article Text |
id | pubmed-9610000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96100002022-10-28 Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate Patera, Jan Němečková, Pavla Zámostný, Petr Pharmaceutics Article Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5–25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion—surface utilization factor—were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing. MDPI 2022-10-12 /pmc/articles/PMC9610000/ /pubmed/36297608 http://dx.doi.org/10.3390/pharmaceutics14102173 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Patera, Jan Němečková, Pavla Zámostný, Petr Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate |
title | Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate |
title_full | Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate |
title_fullStr | Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate |
title_full_unstemmed | Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate |
title_short | Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate |
title_sort | dissolution kinetics of meloxicam formulations co-milled with sodium lauryl sulfate |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9610000/ https://www.ncbi.nlm.nih.gov/pubmed/36297608 http://dx.doi.org/10.3390/pharmaceutics14102173 |
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