Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles

Tarja Limnell; Teemu Heikkilä; Hélder A. Santos; Sanna Sistonen; Sanna Hellstén; Timo Laaksonen; Leena Peltonen; Narendra Kumar; Dmitry Yu. Murzin; Marjatta Louhi-Kultanen; Jarno Salonen; Jouni Hirvonen; Vesa-Pekka Lehto

doi:10.1016/j.ijpharm.2011.06.050

Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles

Tarja Limnell, Teemu Heikkilä, Hélder A. Santos, Sanna Sistonen, Sanna Hellstén, Timo Laaksonen, Leena Peltonen, Narendra Kumar, Dmitry Yu. Murzin, Marjatta Louhi-Kultanen, Jarno Salonen, Jouni Hirvonen, Vesa-Pekka Lehto

Research output: Contribution to journal › Article › Scientific › peer-review

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Abstract

Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30 °C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery.

Original language	English
Pages (from-to)	242-251
Number of pages	10
Journal	International Journal of Pharmaceutics
Volume	416
Issue number	1
DOIs	https://doi.org/10.1016/j.ijpharm.2011.06.050
Publication status	Published - 2011
Publication type	A1 Journal article-refereed

Keywords

Mesoporous silica
Indomethacin
Physical
Chemical
Stability
Drug release
STATE NMR CHARACTERIZATION
DRUG-DELIVERY SYSTEM
POORLY SOLUBLE DRUGS
AMORPHOUS STATE
PORE-SIZE
RELEASE
IBUPROFEN
CRYSTALLIZATION
SPECTROSCOPY
MECHANISM

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10.1016/j.ijpharm.2011.06.050

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Limnell, T., Heikkilä, T., Santos, H. A., Sistonen, S., Hellstén, S., Laaksonen, T., Peltonen, L., Kumar, N., Yu. Murzin, D., Louhi-Kultanen, M., Salonen, J., Hirvonen, J., & Lehto, V.-P. (2011). Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles. International Journal of Pharmaceutics, 416(1), 242-251. https://doi.org/10.1016/j.ijpharm.2011.06.050

@article{dfa2c72bb2ad4373b460f0f90344f324,

title = "Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles",

abstract = "Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30 °C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery.",

keywords = "Mesoporous silica, Indomethacin, Physical, Chemical, Stability, Drug release, STATE NMR CHARACTERIZATION, DRUG-DELIVERY SYSTEM, POORLY SOLUBLE DRUGS, AMORPHOUS STATE, PORE-SIZE, RELEASE, IBUPROFEN, CRYSTALLIZATION, SPECTROSCOPY, MECHANISM",

author = "Tarja Limnell and Teemu Heikkil{\"a} and Santos, {H{\'e}lder A.} and Sanna Sistonen and Sanna Hellst{\'e}n and Timo Laaksonen and Leena Peltonen and Narendra Kumar and {Yu. Murzin}, Dmitry and Marjatta Louhi-Kultanen and Jarno Salonen and Jouni Hirvonen and Vesa-Pekka Lehto",

year = "2011",

doi = "10.1016/j.ijpharm.2011.06.050",

language = "English",

volume = "416",

pages = "242--251",

journal = "International Journal of Pharmaceutics",

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publisher = "Elsevier",

number = "1",

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Limnell, T, Heikkilä, T, Santos, HA, Sistonen, S, Hellstén, S, Laaksonen, T, Peltonen, L, Kumar, N, Yu. Murzin, D, Louhi-Kultanen, M, Salonen, J, Hirvonen, J & Lehto, V-P 2011, 'Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles', International Journal of Pharmaceutics, vol. 416, no. 1, pp. 242-251. https://doi.org/10.1016/j.ijpharm.2011.06.050

TY - JOUR

T1 - Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles

AU - Limnell, Tarja

AU - Heikkilä, Teemu

AU - Santos, Hélder A.

AU - Sistonen, Sanna

AU - Hellstén, Sanna

AU - Laaksonen, Timo

AU - Peltonen, Leena

AU - Kumar, Narendra

AU - Yu. Murzin, Dmitry

AU - Louhi-Kultanen, Marjatta

AU - Salonen, Jarno

AU - Hirvonen, Jouni

AU - Lehto, Vesa-Pekka

PY - 2011

Y1 - 2011

N2 - Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30 °C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery.

AB - Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30 °C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery.

KW - Mesoporous silica

KW - Indomethacin

KW - Physical

KW - Chemical

KW - Stability

KW - Drug release

KW - STATE NMR CHARACTERIZATION

KW - DRUG-DELIVERY SYSTEM

KW - POORLY SOLUBLE DRUGS

KW - AMORPHOUS STATE

KW - PORE-SIZE

KW - RELEASE

KW - IBUPROFEN

KW - CRYSTALLIZATION

KW - SPECTROSCOPY

KW - MECHANISM

U2 - 10.1016/j.ijpharm.2011.06.050

DO - 10.1016/j.ijpharm.2011.06.050

M3 - Article

SN - 0378-5173

VL - 416

SP - 242

EP - 251

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1

ER -

Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles

Abstract

Keywords

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