Control of Physical Forms of Pharmaceutical Substances

Effect of Amino Acids on the Dispersion of Disodium Cromoglycate Powders

“…Unfortunately, the direct measurement of this parameter is impossible. An accepted approach involves analysis of the dispersive component of the surface free energy, γ, and the specific components of surface free energies of adsorption, Δ G A , obtained from inverse gas chromatography (IGC) 15,16. γ can be considered as the portion of the total surface energy constituted by the dispersive van der Waals forces.…”

Influence of Operating Temperature and Pressure on the Polymorphic Transition of Salmeterol Xinafoate in Supercritical Fluids

“…The larger and essentially constant negative ΔG values obtained with the acidic probes (dichloromethane and chloroform) for the samples prepared above the transition temperature at 200 bar (i.e., Form II) indicate that the surface of Form II is predominated by basic forces (from basic groups like CO, NH), which are practically independent of the crystal morphology of the samples prepared under different conditions. As shown elsewhere,12 polymorphism generally occurs as a competition between the thermodynamic factors driving production of the most stable form (at a given temperature) and the crystallization kinetics, which usually acts in the opposite manner. This tendency is often expressed through the Ostwald's rule of successive stages, which states that a polymorphic change will occur stepwise by way of successively more stable phases.…”

“…Crystallization occurs more slowly in the methanol‐rich phase, which is analogous to an increase of the methanol solution feed rate relative to the CO 2 feed. The latter is also known to favor the formation of the more stable form of the enantiotropic polymorph 2, 12. Thus, it becomes apparent that both kinetic and thermodynamic factors are involved in the formation of SX polymorphs.…”

“…This tendency is often expressed through the Ostwald's rule of successive stages, which states that a polymorphic change will occur stepwise by way of successively more stable phases. Such phenomenon has its fundamental explanation in the kinetic theories of crystal growth of polymorphs 12. A high‐energy polymorph usually possesses a surplus of uncompensated polar surface bonds and hence a higher surface energy than the thermodynamically stable form.…”

“…A high‐energy polymorph usually possesses a surplus of uncompensated polar surface bonds and hence a higher surface energy than the thermodynamically stable form. Since the crystal growth rate normally increases with an increase in surface energy, the metastable polymorph would grow faster than the stable form until near equilibrium conditions are reached 12. In the present case with SX, the metastable Form II has a higher energy and more polar surface bonds which are nonsaturated in the CO 2 ‐rich phase, and this probably explains why the conditions of complete miscibility between the two solvent phases involved are crucial for its formation, as reflected by the data in Figure 2.…”