Is equilibrium slurry pH a good surrogate for solid surface pH during drug dissolution?

The purpose of the present study was to investigate the suitability of equilibrium slurry pH (pH) as a surrogate of solid surface pH during drug dissolution (pH). A comprehensive calculation scheme for pH and pH was formalized based on the principle of charge neutrality (equilibrium charge neutrality for pH and charge flux neutrality for pH). The formalized scheme was then used to investigate the validity of pH ≈ pH approximation. The approximation of pH ≈ pH was suggested to be accurate for small molecules (ca. MW = 150) in high concentration buffer media (ca. buffer capacity = 30 mM/ΔpH). In addition, it is valid provided no precipitation of its free form for salts (vice versa for free forms) in both the slurry pH measurement and at the dissolving drug surface. The formalized calculation scheme is simple and applicable to free and salt form drugs in unbuffered and buffered media including bicarbonate buffer. The computational expense is very small so that it is applicable to various computer simulations such as biopharmaceutics modeling and simulation.