Adding a Gastric Step to the Intestinal Digestion Model Improves the Prediction of Pharmacokinetic Data in Beagle Dogs of Two Lipid-Based Drug Delivery Systems.

Drug release from a lipid-based drug delivery system (LbDDS) is typically studied using a one-step intestinal digestion model. However, lately the importance of incorporating gastric digestion has been stressed. The aim of the present study was to compare a two-step gastro-intestinal (GI) digestion model to the commonly used one-step intestinal digestion model. The models were evaluated by studying release of the model drug A1260 from two LbDDSs (F-I and F-II), for which pharmacokinetic data from oral administration to beagle dogs were available. The amount of A1260 recovered in the aqueous phases during and after the GI digestion of F-I and F-II was related to the and AUC of the plasma concentration-time profiles of each formulation and produced a rank order - (IVIV) relation. In comparison, a similar IVIV rank ordering was obtained when relating the amount of A1260 recovered in the aqueous phase prior ( = 0 min), and following 15 min of intestinal digestion, to the plasma concentration-time profiles. However, after 60 min of intestinal digestion, the LbDDSs performed equally in the one-step digestion model, contrary to what was observed in the two-step digestion model, and . As the GI digestion model produced a clearer distinction in terms of LbDDS rank ordering of the two LbDDSs, compared to the intestinal digestion model, it was found to be a promising model to study and estimate the LbDDS behavior .