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Nyvlt, J. ; Institution of Chemical Engineers: Rugby, 2002. 65. Matthews, O. ; Shipway, A. ; Stoddart, J. F. Prog. Polym. Sci. 1998, 23 (1), 1–56. 66. ; Heegaard, P. M. H. Chem. Soc. Rev. 2004, 33 (1), 43–63. 67. ; Windisch, B. Prog. Polym. Sci. 2000, 25 (7), 987–1041. 68. ; Letourneau, J. ; Rodier, E. Powder Technol. 2004, 141 (3), 219–26. 69. Bustami, H. ; Hustert, R. J. Insect Physiol. 2000, 46 (9), 1285–93. 70. Reverchon, E. J. Supercrit. Fluid 1999, 15 (1), 1–21. ; ACS Symposium Series; American Chemical Society: Washington, DC, 2010.

In the hot melt method, drug and water-soluble carrier are melted together at a temperature above the eutectic point (Fig. 4). The most common carrier or matrix phase materials are water soluble polymers such as polyvinyl pyrollidone (PVP) (25), (polyethylene glycol (PEG) (26), hydroxypropylcellulose (HPC) (27), chitosan (28), and gelatin (29). These polymers have the advantages that they are biocompatible, solubilize many hydrophobic drugs in the molten form, and upon cooling they uniformly transition from a liquid to a solid glass.

They are protected from aggregation and sterically stabilized by the hydrophilic portion of the block copolymer (53–58). These differ from traditional micellar nanoparticle formation methods such as direct solution or dialysis methods in terms of the dynamics of the process (56): the rapid mixing and precipitation produces nanoparticles that are in a kinetically trapped (frozen) rather than at equilibrium. This non-equilibrium process offers more control and flexibility of size and chemistry because assembly is governed not just by thermodynamic conditions but by the entire process history (59).

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