Solubilization and interaction of sulindac with polyvinylpyrrolidone K30 in the solid state and in aqueous solution.

In this report the interactions of sulindac with polyvinylpyrrolidone K30 (PVP K30), both in the solid state and in aqueous solution, have been investigated. Solid dispersions of sulindac with PVP K30 were prepared by the solvent method in ethanol from various drug-to-polymer weight ratios. X-ray powder diffraction and differential scanning calorimetry have shown that PVP inhibits the crystallization of sulindac. The stabilization of the noncrystalline state of sulindac was shown by x-ray diffractometry after a 1-year storage. There was a considerable increase in the release rate of the drug when the polymer content was increased and the intrinsic dissolution rate values of these systems were calculated. From the UV spectra a bathochromic shift and a well-defined isosbestic point were observed at pH 2 and 6, which confirmed an interaction between the drug and the polymer in solution. Moreover, the apparent solubility of sulindac has been modified as a function of the polymer concentrations. The binding process between the drug and PVP was exothermic from the stability constant values at 25, 30, and 37 degrees C at pH 2.

Solubilization and interaction of sulindac with beta-cyclodextrin in the solid state and in aqueous solution.

A sulindac-beta-cyclodextrin complex was obtained by the coprecipitation method. Kneaded solids and physical mixtures were also prepared. The complex was shown by x-ray powder diffraction to be noncrystalline whereas pure drug and any of the other sulindac-beta-CD system were crystalline. the endothermic peak of sulindac due to the fusion of drug disappeared in DSC thermograms for the coprecipitate product, which confirmed the interaction between sulindac and beta-CD in the solid state. After a 1-year storage drug crystals could not be observed by x-ray diffractometry, which indicated that the complex formed was stable. The complex showed the fastest dissolution rate which might be attributed to the high-energy noncrystalline state and the inclusion complex formation in solution. UV spectra were modified and the apparent solubility of the drug increased with the addition of beta-CD, which confirmed the interaction between sulindac and the ligand in solution. The apparent stability constant, K1:1, for the complex at pH 2 and 25, 30, and 37 degrees C was 340, 220, and 160 M-1, respectively, which confirmed the influence of temperature on the complex stability. The value of K1:1 at pH 6 and 25 degrees C was 139 M-1, which indicated that the complex is formed easier with the non-ionized sulindac. The enthalpy change, delta H degree, showed that the binding process is exothermic.

Polymorphism of sulindac: isolation and characterization of a new polymorph and three new solvates.

The polymorphism of sulindac was investigated. Two polymorphs (I and II) and a new crystalline form (form III) of sulindac were prepared by recrystallization in different solvents. In addition, three new pseudopolymorphs (solvates) from acetone, chloroform, and benzene were obtained, with each containing 1 mol of solvent to 2 mol of sulindac. Different sulindac polymorphs and pseudopolymorphs were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and hot-stage microscopy. The transition behavior of the crystalline forms of sulindac, their melting points, and their enthalpies were investigated by DSC. The melting of form II was observed at 184 degrees C, and form I subsequently recrystallized from this melt. Similarly, form III melts at 145 degrees C and then recrystallizes to form I. We also investigated the influence of the crystallization solvent on sulindac crystal shape.