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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Godec
Aljaz
A
National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
Maver
Uros
U
Bele
Marjan
M
Planinsek
Odon
O
Srcic
Stane
S
Gaberscek
Miran
M
Jamnik
Janko
J
D003460:Crystallization; D004055:Differential Thermal Analysis; D004337:Drug Carriers; D005782:Gels; D009543:Nifedipine / Q000737:chemistry*; D016062:Porosity; D033362:Powder Diffraction; D012822:Silicon Dioxide / Q000737:chemistry*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D004337:Drug Carriers; D005782:Gels; D012822:Silicon Dioxide; D009543:Nifedipine