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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...

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Autores principales: Patera, Jan, Němečková, Pavla, Zámostný, Petr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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