Drug-polymer miscibility

Djuris, J. Nikolakakis, I. Ibric, S. Djuric, Z. Kachrimanis, K. Preparation of carbamazepine-Solup-lus solid dispersions by hot-melt extrusion, prediction of drug-polymer miscibility by thermodynamic model fitting. Eur. J. Pharm. Biopharm. 2013, 84(1), 228-237. 

Predictive models for drug-polymer miscibility have been introduced, and they are largely derived from solution thermodynamics. Lattice-based solution models, such as the F-H theory, can be used to assess miscibility in drug-polymer blends, for which the F-H interaction parameter can be considered as a measure of miscibility. In addition, solubility parameter models can be used for this purpose. The methods used to estimate interaction parameters include melting point depression and the determination of solubility parameters using group contribution theory. 

Marsac PJ, Konno H, Taylor LS (2006a) A comparison of the physical stability of amorphous felodipine and nifedipine systems. Pharm Res 23(10) 2306-2316 Marsac PJ, ShambRn SL, Taylor LS (2006b) Theoretical and practical approaches for prediction of drug-polymer miscibility and solubility. Pharm Res 23(10) 2417-2426 Marsac PJ, Li T, Taylor LS (2009) Estimation of drug-polymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm Res 26(1) 139-151... 

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

Figure 5.4 Composition vs temperature diagram illustrating the concepts of drug solubility, and drug-polymer miscibility in relation to the binary system s glass transition temperature. Reprinted with permission from [28], Copyright 2010 Wiley.

The upper drug-polymer miscibility boundary (spinodal curve. Figure 5.4) can be estimated by setting the second derivative of the free energy of mixing equal to zero ... 

P.J. Marsac, S.L. Shamblin, and L.S. Taylor, Theoretical and practical approaches for prediction of drug-polymer miscibility and solubility, Pharm Res, 23 (10), 2417-26,2006. 

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