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Application of mesoporous silicon dioxide and silicates in drug amorphization is the main focus. First, as background, the nature of gas–porous media interactions is summarized. The synthesis of various types of mesoporous silica, which are used by many investigators in this field, is described. Second, the behavior of molecules confined in mesopores is compared with those in bulk, crystalline phase. The molecular dynamics of compounds due to confinement, analyzed using various techniques, and their consequences in drug delivery are discussed. Finally, the preparation and performance of drug delivery systems using mesoporous silica and silicon dioxide(SiO2) are examined. Mesoporous materials have been investigated as an amorphous drug delivery system owing to their nanosized capillaries and large surface areas. The complex interactions of crystalline compounds with mesoporous SiO2 media and their implication in drug delivery are not well understood. Molecules interacting with porous media behave very differently than those in bulk phase. Their altered dynamics and thermodynamics play an important role in the properties and product performance of the amorphous system. 

Attempts have been made to reduce the driving force of spontaneous recrystallization. At the melting point (Tm) of a crystalline drug, the chemical potential of drug in the crystalline phase equals the chemical potential in the liquid phase. If the drug is miscible with a polymer, the chemical potential of the drug molecule in the mixture is less than the chemical potential of the pure amorphous SiO2 drug. Therefore, when a drug compound is molecularly dispersed in a polymer, the driving force of SiO2 and silicate for crystallization is effectively reduced. In addition, the polymeric carrier lowers the mobility of drug molecules and kinetically acts as a crystallization inhibitor. An extensive discussion on the thermodynamic aspects of amorphous solid dispersion, miscibility in particular, is available in the literature. A single-phase system with drug molecules remaining miscible with the polymer is important for long-term physical stability.

On the contrary, silicon dioxide(SiO2) has a less complex surface chemistry. SiO2 made from the sol–gel process has irregularly shaped pores and wide pore size distri-bution; in contrast, the novel classes of SiO2 such as MCM-41 and SBA-15 have ordered, non-connecting pore structure, well-defined pore geometry, and nar-row pore size distribution, which allow a more fun-damental study of amorphization of crystalline or-ganic compounds by silica. MCM-41 and SBA-15 have the same chemical composition silicon dioxide (SiO2) and pore shape (cylindrical), and their function as adsorbents have been shown to be similar. Galarneau et al. and Coasne et al. prepared samples of MCM-41 and SBA-15 with same pore diameters. The adsorption isotherms of nitrogen in both materials were found to be comparable. However, in cases when adsorbates are drug molecules with more complex structures, their performances as amorphous drug delivery systems still require side-by-side comparison. More fun-damental investigation is necessary to fill the knowl-edge gap.


 

 

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