Characterization of the Precipitates of Poorly Water Soluble Drugs and Determination of the Solubilities in Human Gastro-Intestinal Fluids by Microsopy

Gastrointestinal (GI) fluids were collected from 5 volunteers, and the pH of each fluid measured. Solutions of poorly water soluble sompounds in polyethylene glycol 400 (PEG-400) and absolute ethanol were introduced in measured aliqouts, to 2 mL portions of the GI fluids that were preheated to 37 C. The fluids were examined microscopically after each addition to determine the solubility of the drugs in those fluids and what type of precipitate would result. Melting temperatures of the compounds ranged from 40 C to 200 C. In all cases, the precipitate formed oily droplets in the GI fluids when the solubility limit was exceeded. Oily droplet formation was independent of molecular structure, melting temperature, and fluid pH. Compounds of low water solubility would be expected to form oily droplets in biological fluids, which would enhance absorption regardless of pH. GI fluid pH values were found to vary widely among individual samples from 1.49 to 7.08 (gastric) and 2.18 to 7.06 (intestinal).