Computational oral absorption simulation of free base drugs

The purpose of the present study was to investigate the oral absorption simulation of free base drugs. In the case of a low solubility free base drug, a portion of drug particles remains incompletely dissolved during the stomach transit and can reach the small intestine. As the pH is neutralized in the small intestine, the solubility of the drug decreases and the concentration gradient around the particles becomes a negative value. The drug particles would then grow because of this negative concentration gradient resulting in a reduction of the dissolved drug concentration. The modified Nernst Brunner equation was used to simulate both particle dissolution and growth (particle growth is the opposite phenomena of particle dissolution). Albendazole, aprepitant, dipyridamole, gefitinib and ketoconazole were used as model drugs (all free solid form (not salts)). The effect of stomach pH on oral absorption was appropriately simulated. Based on the simulation results, it was suggested that the dissolution patterns in the gastrointestinal tract were significantly different depending on the dose–solubility ratio in the stomach.