Crystallization of Piroxicam Solid Forms and the Effects of Additives

The relative stabilities of the two anhydrous polymorphs and the monohydrate of piroxicam in ethanol/water mixtures and the crystallization behavior of the solid forms in the presence of 11 additives were studied. At 37 °C, form II is thermodynamically more stable than form I, while the relative stability of form II and the monohydrate depends on the water concentration in the solution. The total Hansen solubility parameter δT and the hydrogen bonding solubility parameter δH of the substances can partly explain the effects of the additives on the crystallization of the solid forms. The additives that selectively promoted the crystallization of form I are the ones with δT and δH parameters similar to those of piroxicam. Solid form selection can help improve the solubility and dissolution rate of poorly water‐soluble drug candidates. The relative stabilities of the anhydrous and monohydrate solid forms of piroxicam in ethanol/water mixtures were studied. The validity of the Hansen solubility parameter in the preliminary screening of additives for controlling the piroxicam solid form during crystallization is demonstrated.