Prediction of Liquid-Liquid Phase Separation at the Dissolving Drug Salt Particle Surface.

During the dissolution of drug salt particles, liquid-liquid phase separation (LLPS) of a free form can occur within the unstirred water layer (UWL) of the particles (UWL-LLPS). Theoretically, UWL-LLPS occurs when the free form concentration at the salt particle surface () exceeds the intrinsic LLPS concentration () of the free form. In the present study, we attempted to predict UWL-LLPS based on the intrinsic physicochemical properties of drugs.

Thermodynamic Correlation between Liquid-Liquid Phase Separation and Crystalline Solubility of Drug-Like Molecules.

The purpose of the present study was to experimentally confirm the thermodynamic correlation between the intrinsic liquid−liquid phase separation (LLPS) concentration (S0LLPS) and crystalline solubility (S0c) of drug-like molecules. Based on the thermodynamic principles, the crystalline solubility LLPS concentration melting point (Tm) equation (CLME) was derived (log10S0C=log10S0LLPS−0.0095Tm−310 for 310 K).

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.

Effects of Coformer and Polymer on Particle Surface Solution-Mediated Phase Transformation of Cocrystals in Aqueous Media.

The purpose of the present study was to investigate the effect of the coformer difference on particle surface solution-mediated phase transformation (PS-SMPT) during cocrystal particle dissolution in aqueous media in the absence and presence of polymers. SMPT can occur either in the bulk phase or at the particle surface because drug molecules can be supersaturated at the dissolving cocrystal surface, as well as in the bulk phase. Previously, bulk phase SMPT has been primarily investigated in formulation development.

Mechanism of Supersaturation Suppression in Dissolution Process of Acidic Drug Salt.

Supersaturable active pharmaceutical ingredients (sAPI), such as salts, cocrystals, and amorphous solids, can form supersaturated solutions after dissolving in the gastrointestinal fluids. However, there are cases in which supersaturation is not observed in an in vitro nonsink dissolution test. The purpose of the present study was to investigate the mechanisms of supersaturation suppression in the dissolution process of acidic drug salts.

Precipitation behavior of pioglitazone on the particle surface of hydrochloride salt in biorelevant media.

The purpose of the present study was to investigate the precipitation of a drug on the particle surface of its salt in biorelevant media. Pioglitazone (PIO, weak base, pK = 5.8) was used as a model drug.