Vitrification from solution in restricted space: Formation and stabilization of amorphous nifedipine in a nanoporous silica xerogel carrier

The goal was to find thermodynamic criteria that must be satisfied in order to prevent formation of crystalline state of drugs within a confined space (e.g., nanopores of inorganic solid). Similarly, criteria that lead to stabilization of amorphous drug within such pores were investigated. In the th...

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Bibliographic Details
Published in:International journal of pharmaceutics 2007-10, Vol.343 (1), p.131-140
Main Authors: Godec, Aljaž, Maver, Uroš, Bele, Marjan, Planinšek, Odon, Srčič, Stane, Gaberšček, Miran, Jamnik, Janko
Format: Article
Language:English
Subjects:
Amorphous drugs
Biological and medical sciences
Crystallization
Differential Thermal Analysis
Drug Carriers
Gels
General pharmacology
Medical sciences
Nifedipine - chemistry
Nucleation
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Porosity
Porous carriers
Powder Diffraction
Silicon Dioxide - chemistry
Structural stabilization
Thermodynamics
Thermogravimetry
X-Ray Diffraction
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Summary:The goal was to find thermodynamic criteria that must be satisfied in order to prevent formation of crystalline state of drugs within a confined space (e.g., nanopores of inorganic solid). Similarly, criteria that lead to stabilization of amorphous drug within such pores were investigated. In the theoretical part, the classical thermodynamics of nucleation is applied to the conditions of a restricted space. The theoretical findings are verified using porous silica as a carrier and nifedipine as a model drug. The amorphicity of the latter is checked using XRD and thermal analysis (DTA, DSC) in combination with BET measurements. It is shown that there exists a critical pore radius of a host below which the entrapped substance will solidify in an amorphous form. There also exists a critical pore radius below which the entrapped amorphous solid will not be able to crystallize. Specifically, incorporation of NIF into a silica xerogel with an average pore diameter of about 2.5 nm produces and stabilizes its amorphous form. Entrapment of drugs into solid nanoporous carriers could be regarded as a potentially useful and simple method for production and/or stabilization of non-crystalline forms of a wide range of drugs.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2007.05.022