Interest of molecular/crystalline dispersions for the determination of solubility curves of drugs into polymers

M. Latreche (1) , Jean-François Willart (2, 1) , M. Guerain (3, 1) , F. Danède (2, 1) , Alain Hédoux (2, 1)

1 UMET - Unité Matériaux et Transformations - UMR 8207
2 LDSMM - Laboratoire de dynamique et structure des matériaux moléculaires
3 LaSIE - Laboratoire des Sciences de l'Ingénieur pour l'Environnement - UMR 7356

We present here a method to increase the dissolution rate of drugs into polymers in order to make easier and faster the determination of the solubility curves of these mixtures. The idea is to prepare molecular/crystalline dispersions (MCD) where the drug is dispersed into the polymer, partly at the molecular level and partly in the form of small crystallites. We show that this particular microstructure greatly increases the dissolution rate of crystallites since: (1) The molecular dispersion has a plasticizing effect which greatly increases the molecular mobility in the amorphous matrix. (2) The fine crystallite dispersion in the matrix strongly reduces the distances over which the drug molecules have to diffuse to invade homogeneously the polymer by dissolution. MCD are here obtained by combining solid-state co-amorphization by high energy mechanical milling and then recrystallization by annealing under a plasticizing atmosphere. We have used MCD to determine the solubility lines of the two polymorphic forms (I and II) of sulindac into PVP. The investigations have been performed mainly by DSC and powder x-ray diffraction.

Domains: Soft Condensed Matter [cond-mat.soft]; Pharmaceutical sciences

M. Latreche, Jean-François Willart, M. Guerain, F. Danède, Alain Hédoux. Interest of molecular/crystalline dispersions for the determination of solubility curves of drugs into polymers. International Journal of Pharmaceutics, 2019, 570, pp.118626. ⟨10.1016/j.ijpharm.2019.118626⟩. ⟨hal-02363477⟩