Compaction properties of powders: the relationship between compression cycle hysteresis areas and maximally applied punch pressures.

The consolidation behaviors of various pharmaceutical solids were characterized by investigating the relationship between the calculated hysteresis areas and the maximally applied punch pressures. An Instron universal testing apparatus and an instrumented die were used to generate compression cycle profiles at various maximally applied punch pressures for the materials studied. Based on the profiles obtained, hysteresis areas were calculated for the materials studied as a function of maximally applied punch pressures. Furthermore, model profiles describing the plastic and brittle fracture processes were utilized to derive mathematical relationships between the calculated hysteresis cycle areas and the maximally applied punch pressures. The mathematical relationships derived indicate that a linear relationship between hysteresis areas and maximally applied punch pressures exists for plastic materials, whereas for brittle materials the hysteresis areas are related to the square of the maximally applied punch pressures. Experimental data obtained support the mathematical relationships derived. The goodness of fit to the models derived is used to rank order the consolidation mechanism of various drugs and pharmaceutical excipients.

Consolidation mechanisms of pharmaceutical solids: a multi-compression cycle approach.

PURPOSE: The consolidation behavior of various pharmaceutical solids were characterized using compression-cycle profiles. Compression-cycle profiles for both uncompacted powder and formed tablets were obtained. These profiles were used to qualitatively and quantitatively characterize the consolidation mechanism of pharmaceutical solids. METHODS: An Instron Universal Testing apparatus and a specially instrumented die coupled with a computerized data acquisition system were utilized to measure the upper-punch pressure and the corresponding die-wall pressure during the compression cycle. RESULTS: Compression cycle profiles were obtained for a variety of pharmaceutical materials. Based on these profiles, parameters such as hysteresis areas, loading slopes, and unloading slopes were calculated for the materials studied. CONCLUSIONS: Materials that consolidate by plastic deformation have similar compression cycle profiles for the first and subsequent compression cycles indicating that the plastic deformation process occurs to the same extent on the first as well as subsequent compression cycles. For brittle materials, the brittle fracture process occurs during the first compression cycle. During subsequent cycles the tabletted material does not undergo further yield or failure and primarily undergoes elastic deformation. Low molecular-weight polyethylene glycol is an excellent model material for plastically deforming materials, whereas sucrose or sodium citrate are excellent examples of materials that consolidate by brittle fracture.

Solvent effects on chemical processes. V: Hydrophobic and solvation effects on the solubilities of substituted biphenyls in methanol/water mixtures.

A phenomenological model that permits solvent effects to be separated into general medium effects (the solvophobic effect) and solvation effects is applied to the solubility of a series of biphenyl compounds in methanol/water mixtures. The parameters of the model (gA, K1, and K2, K1 and K2 are equilibrium constants for solvation and gA describes the general medium contribution) were evaluated from the nonlinear regression of the model equation to the data. It was found that the surface tension curvature factor (g) was 0.37, that A represents the hydrophobic (nonpolar) surface area of the solute molecule, and that K1 and K2 were 2.53 and 1.77 (means for solutes in methanol/water), respectively. These results permit solvent effects on solubility in methanol/water to be predicted and they refine the interpretation of the solvent effect model.

Solvent effects on chemical processes. I: Solubility of aromatic and heterocyclic compounds in binary aqueous-organic solvents.

The standard free energy change (delta G0) for equilibrium dissolution in binary solvent mixtures is written as a sum of effects arising from solvent-solvent interactions (the general medium effect), solvent-solute interactions (the solvation effect), and solute-solute interactions (the intersolute effect). The general medium effect is given by gA gamma, where g is a curvature correction factor to the surface tension (gamma) and A is the molecular cavity surface area. A new feature is the definition of gamma to be that value appropriate to the equilibrium mean solvation shell composition. The solvation effect is modeled by stoichiometric stepwise competitive equilibria between the two solvent components for the solute. The intersolute effect includes the crystal energy and solution phase interactions. In this work, water was solvent component 1, and various miscible organic cosolvents served as solvent component 2. Relating all data to the fully aqueous solution gives an explicit expression for delta M delta G0, the solvent effect on the free energy change, as a function of the mole fractions x1 and x2. This function is a binding isotherm. Nonlinear regression leads (for a two-step solvation scheme) to estimates of the solvation exchange constants K1 and K2 and the parameter gA. This relationship was applied to 44 systems comprising combinations of 31 solutes and eight organic cosolvents. Curve fits were good to excellent, and most of the parameter estimates had physically reasonable magnitudes.