Application of an Artificial Stomach-Duodenum Reduced Gastric pH Dog Model for Formulation Principle Assessment and Mechanistic Performance Understanding.

The objective of this study was to develop an artificial stomach-duodenum (ASD) dissolution model as an in vitro evaluation tool that would simulate the gastrointestinal physiology of gastric pH-reduced dogs as a method to assess formulations for a poorly soluble free acid compound with ng/mL solubility. After establishing the ASD model with well-controlled duodenum pH, 5 formulations each applying different solubilization principles were developed and their performance in the ASD model and in vivo in dogs was evaluated. Excellent correlations were obtained between dog area under the curve (AUC) and ASD AUC of 5 formulations evaluated with simulated intestinal fluid (r = 0.

The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

Purpose: The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs.

Methods: The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate.