Drug-excipient miscibility

Konno H, Taylor LS (2006) Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. J Pharm Sci 95 2692-2705 Konno H, Handa T, Alonzo DE, Taylor LS (2008) Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. Eur J Pharm Biopharm 70 493 99 Lauer ME, Grassmann O, Siam M, Tardio J, Jacob L, Page S et al (2011) Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions. Pharm Res 28 572-584... 

Lauer ME, Grassmann O, Siam M, Tardio J, Jacob L, Page S, Kindt JH, Engel A, Alsenz J (2011) Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions. Pharm Res 28 572-584... 

Keywords Hot-melt extrusion, thermoplastic polymers, drug-polymer miscibility, polymer matrix, polymeric excipients, sohd dispersions, solid solutions... 

If the components are not miscible in the solid and the liquid states, their DSC peaks remain unchanged. This allows to identify components of the drug product, to follow aging problems with polymorphism and in favourable cases to quantify the drug substance and the excipients.f ° ... 

Drug substance properties should be carefully evaluated. These property will dictate the excipients, method, and process selection for ASD product. The properties to be considered are solubility in organic and aqueous solvents, miscibility with polymers, melting point, particle size, and thermal stability. These properties determine manufacturability, product performance, and long-term stability. For example, hot melt extrusion cannot be used for thermally labile drug molecules (Forster et al. 2001 Vasconcelos et al. 2007 Leuner and Dressman 2000). Qn the other hand, for spray drying process, drug solubility determines the selection of the solvent as well as inlet process temperature (Vasconcelos et al. 2007 Leuner and Dressman 2000). 

The studies above revealed that a low molecular excipient such as citric acid can be used for the stabilization of an amorphous drug, even though its own Tg (11 °C) is rather low (Hoppu et al. 2007). Specific molecular interactions seemed to be the main stabilization mechanism. However, it was also shown that limited solid-state miscibility between drug and citric acid can lead to phase separation, which can be the starting point of crystallization. 

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