Probing the Effect of Drug Loading and Humidity on the Mechanical Properties of Solid Dispersions with Nanoindentation: Antiplasticization of a Polymer by a Drug Molecule
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作者:
Lamm, Matthew S.
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Merck & Co Inc, Merck Res Labs, Summit, NJ 07901 USAMerck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
Lamm, Matthew S.
[1
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Simpson, Amanda
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Hysitron Inc, Nanomech Res Lab, Minneapolis, MN USAMerck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
Simpson, Amanda
[2
]
McNevin, Michael
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Merck & Co Inc, Merck Res Labs, Summit, NJ 07901 USAMerck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
McNevin, Michael
[1
]
Frankenfeld, Celeste
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Merck & Co Inc, Merck Res Labs, Summit, NJ 07901 USAMerck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
Frankenfeld, Celeste
[1
]
Nay, Richard
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Hysitron Inc, Nanomech Res Lab, Minneapolis, MN USAMerck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
Nay, Richard
[2
]
Variankaval, Narayan
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Merck & Co Inc, Merck Res Labs, Summit, NJ 07901 USAMerck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
Variankaval, Narayan
[1
]
机构:
[1] Merck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
[2] Hysitron Inc, Nanomech Res Lab, Minneapolis, MN USA
Amorphous solid dispersions of clotrimazole in the polymer Kollidon VA64 were prepared as films in concentrations from 0% to 100% in 10% by weight increments. Nanoindentation was performed on each film at 18% and 49% relative humidity to assess the effect of drug loading and humidity on the mechanical properties of the solid dispersions. Although the addition of clotrimazole to the polymer reduces the glass transition temperature of the system as measured by differential scanning calorimetry, the hardness, reduced elastic modulus, and storage modulus were found to increase to values greater than those of either pure component up to drug loadings of approximately 60% by weight. Further addition of clotrimazole to the system resulted in decreased hardness and moduli with increased drug load. Dynamic vapor sorption of the dispersions shows that the hygroscopicity of the system is reduced as clotrimazole is added to the polymer.
机构:
Inst Surface Chem, YKI, SE-11486 Stockholm, Sweden
Royal Inst Technol, Dept Chem, Div Phys Chem, SE-10044 Stockholm, Sweden
Royal Inst Technol, Dept Chem, Ind NMR Ctr, SE-10044 Stockholm, SwedenInst Surface Chem, YKI, SE-11486 Stockholm, Sweden
Dahlberg, Carina
Millqvist-Fureby, Anna
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Inst Surface Chem, YKI, SE-11486 Stockholm, SwedenInst Surface Chem, YKI, SE-11486 Stockholm, Sweden
Millqvist-Fureby, Anna
Schuleit, Michael
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Novartis Pharma AG, Pharmaceut & Analyt Dev, CH-4056 Basel, SwitzerlandInst Surface Chem, YKI, SE-11486 Stockholm, Sweden
Schuleit, Michael
Furo, Istvan
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Royal Inst Technol, Dept Chem, Div Phys Chem, SE-10044 Stockholm, Sweden
Royal Inst Technol, Dept Chem, Ind NMR Ctr, SE-10044 Stockholm, SwedenInst Surface Chem, YKI, SE-11486 Stockholm, Sweden
机构:
Genentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USAGenentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USA
Zhang, Wei
Sluga, Kellie K.
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Genentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USAGenentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USA
Sluga, Kellie K.
Yost, Edward
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Genentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USAGenentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USA
Yost, Edward
Phan, Jerry
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Genentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USAGenentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USA
Phan, Jerry
Nagapudi, Karthik
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Genentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USAGenentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USA
Nagapudi, Karthik
Hou, Hao Helen
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Genentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USAGenentech Inc, Small Mol Pharmaceut Sci, 1 DNA Way, South San Francisco, CA 94080 USA
机构:
Beijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R ChinaBeijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China
Wang, Qi Lei
Ren, Jia Wei
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机构:
North China Elect Power Univ Hosp, Beijing 102206, Peoples R ChinaBeijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China
Ren, Jia Wei
Chen, Bo Zhi
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Beijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R ChinaBeijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China
Chen, Bo Zhi
Jin, Xuan
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Beijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R ChinaBeijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China
Jin, Xuan
Zhang, Can Yang
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机构:
Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA 99210 USABeijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China
Zhang, Can Yang
Guo, Xin Dong
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Beijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R ChinaBeijing Univ Chem Technol, Coll Mat Sci & Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China