Melt-electrospinning as a method to improve the dissolution and physical stability of a poorly water-soluble drug

The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus® (SOL) were prepare...

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Published inEuropean journal of pharmaceutical sciences Vol. 121; pp. 260 - 268
Main Authors Semjonov, Kristian, Lust, Andres, Kogermann, Karin, Laidmäe, Ivo, Maunu, Sirkka Liisa, Hirvonen, Sami-Pekka, Yliruusi, Jouko, Nurk, Gunnar, Lust, Enn, Heinämäki, Jyrki
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 30.08.2018
Subjects
Drug-polymer interactions
Indomethacin
Melt electrospinning
Melt-spun fibers
Poorly water-soluble drug
Soluplus
Poorly water-soluble drug
Soluplus
Indomethacin
Drug-polymer interactions
Melt electrospinning
Melt-spun fibers
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Abstract The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus® (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(1H), and the domain size of IND in MSFs (25–100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL). [Display omitted]
AbstractList The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus® (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1( H), and the domain size of IND in MSFs (25-100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL).
The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus® (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(1H), and the domain size of IND in MSFs (25–100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL). [Display omitted]
Author Lust, Andres
Laidmäe, Ivo
Hirvonen, Sami-Pekka
Lust, Enn
Kogermann, Karin
Yliruusi, Jouko
Maunu, Sirkka Liisa
Heinämäki, Jyrki
Semjonov, Kristian
Nurk, Gunnar
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Keywords Poorly water-soluble drug
Soluplus
Indomethacin
Drug-polymer interactions
Melt electrospinning
Melt-spun fibers
Language English
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Snippet The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and...
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SubjectTerms Drug-polymer interactions
Indomethacin
Melt electrospinning
Melt-spun fibers
Poorly water-soluble drug
Soluplus
Title Melt-electrospinning as a method to improve the dissolution and physical stability of a poorly water-soluble drug
URI https://dx.doi.org/10.1016/j.ejps.2018.06.004
https://www.ncbi.nlm.nih.gov/pubmed/29883725
https://search.proquest.com/docview/2052809348
Volume 121
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