Amorphous solid screening

I See the Saunders Interactive General Chemistry CD-ROM, Screen 13.12, Solid Structures (1) Crystalline and Amorphous Solids. 

Fig. 5.7 How chart of miniaturized screening to evaluate amorphous solid dispersion preparation and processing methods...

Hancock BC, Shamblin SL, Zografi G (1995) Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res 12 799-806 Hu Q, Choi DS, Chokshi H, Shah N, Sandhu H (2013) Highly efficient miniaturized coprecipitation screening (MiCoS) for amorphous solid dispersion formulation development. Int J Pharm 450 53-62... 

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... 

Van Eerdenbmgh B, Taylor LS (2010) Small scale screening to determine the ability of different polymers to inhibit dmg crysUillization upon rapid solvent evaporation. Mol Pharm 7 1328—1337 Van Eerdenbmgh B, Taylor LS (2011) An ab initio polymer selection methodology to prevent crystallization in amorphous solid dispersions by application of crystal engineermg principles. Cryst Eng Comm 13 6171-6178... 

Other, more recently created amorphous solids have been placed in many important applications. Amorphous semiconductors are used in electronic devices, including solar cells, copiers, laser printers, and flat-panel displays for computer monitors and television screens. 

Solubility is highly influenced by the solid-state form (e.g., crystalline or amorphous) of the drug. Rigorous solubility studies using the final solid form (i.e., salt form or crystal form) as a function of temperature (i.e., 25 and 37°C) and pH (range 1 to 7.5) are conducted during preformulation. Solubility in nonaqueous solvents is also screened. Solubility in simulated gastrointestinal fluids is also important. 

Cefoxitin is a broad spectrum, semi-synthetic cephamy-cin antibiotic. The free acid form is a white, crystalline, practically insoluble solid and therefore the decision was made to use the sodium salt to provide a sterile solution for intravenous administration. It was soon evident that the sodium salt of cefoxitin would have limited stability in solution and would not lend itself to the formulation of a marketable solution product. Stability studies highlighted the advantages of sterile crystalline solid over amorphous freeze-dried product, and also the need for rubber stopper screening studies to eliminate interactions between sodium cefoxitin powder and rubber, and finally the profound effect of oxygen on the coloration rate of the product. 

Given all the possible structures available to an organic solid, form selection can be a daunting task. The process typically begins once the molecular structure of the active has been selected, but can also accompany salt selection (see above). The first step in solid form selection is to determine if polymorphic and/or amorphous forms of the molecule of interest (drug substance) exist. This process is called polymorph screening (46). Once forms are identified, they must be characterized and their important properties determined. Only with such data in hand can a rational selection of final solid form be made. 

Wyttenbach N, Janas C, Siam M, Lauer ME, Jacob L, Scheubel E, Page S (2013) Miniaturized screening of polymers for amorphous drug stabilization (SPADS) rapid assessment of solid dispersion systems. Eur J Pharm Biopharm 84(3) 583-598... 

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