Analysis of the Dissolution Mechanism of Drugs into Polymers: The Case of the PVP/Sulindac System.

This paper is dealing with the dissolution mechanism of crystalline sulindac into amorphous Polyvinylpyrrolidone (PVP) upon heating and annealing at high temperatures. Special attention is paid on the diffusion mechanism of drug molecules in the polymer which leads to a homogeneous amorphous solid dispersion of the two components. The results show that isothermal dissolution proceeds through the growth of polymer zones saturated by the drug, and not by a progressive increase in the uniform drug concentration in the whole polymer matrix.

Contribution of low-frequency Raman spectroscopy to determine the solubility curves of drugs in polymers: The case of paracetamol/PVP.

A new method for determining solubility lines of drugs in polymers, based on low-frequency Raman spectroscopy measurements, is described and the results obtained by this method are compared with those obtained using a more classical method based on differential scanning calorimetry investigations. This method was applied to the paracetamol/PVP system using molecular and crystalline dispersions (MCD) rather than usual physical mixtures to reach faster the equilibrium saturated states and make the determination of the solubility line more rapid.

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

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.

Polymorphism versus devitrification mechanism: Low-wavenumber Raman investigations in sulindac.

The polymorphism of sulindac was investigated by Raman investigations, mainly in the low-wavenumber region in order to analyze the influence of the amorphization method on recrystallization and crystalline form stability. By devitrification of the quenched liquid, it was found that the undercooled liquid crystallizes into Form I, and a polymorphic transformation by cooling Form I toward Form IV, was clearly revealed. The low-wavenumber spectra of polymorphic forms are direct fingerprints of crystals, indicating a degree of disorder of Form IV intermediate between those of the ordered Form II (commercial form) and the relatively disordered Form I.

Using Milling to Explore Physical States: The Amorphous and Polymorphic Forms of Sulindac.

This article shows how milling can be used to explore the phase diagram of pharmaceuticals. This process has been applied to sulindac. A short milling has been found to trigger a polymorphic transformation between form II and form I upon heating which is not seen in the nonmilled material.