The Dynamic Intestinal Absorption Model (Diamod®), an in vitro tool to study the interconnected kinetics of gastrointestinal solubility, supersaturation, precipitation, and intestinal permeation processes of oral drugs

Contribution of the Dynamic Intestinal Absorption Model (Diamod) to the Development of a Patient-Centric Drug Formulation

“…Furthermore, an absorptive compartment is implemented in the duodenal vessel, containing a realistic surface area available for absorption with respect to the duodenal fluid volume (ratio 2 cm −1 ). 34 When exploring the effect of gastric pH on the intestinal absorption of compound X in this sophisticated in vitro model, a clear effect was predicted on the gastric dissolution kinetics, thereby affecting intestinal concentrations and the subsequent permeation rate over the dialysis membrane. More specifically, permeated concentrations decreased by 35% under hypochlorhydric conditions (permeated concentrations after 60 min: 1.4 vs 0.9 μg/mL when exposed to gastric pH 1.6 vs pH 5.0, respectively) and even by 79% under achlorhydric conditions (permeated concentrations after 60 min: 1.4 vs 0.3 μg/mL when exposed to gastric pH 1.6 vs pH 7.0, respectively).…”

“…In order to steer the patient-centric formulation development of compound X, different sets of experiments were performed in the Diamod. The general features and operating procedures of the Diamod have been previously described in detail . Different drug formulations of compound X were tested, including (i) HPMC capsules containing granules of compound X, (ii) HPMC capsules containing granules of compound X and pH-modifier 1 or pH-modifier 2, (iii) monolayer tablets containing a mixture of compound X and pH-modifier 1, and (iv) bilayer tablets containing compound X and pH-modifier 1. pH-modifiers 1 and 2 are diprotic organic acids with p K a1 and p K a2 ranging between 2.5 and 4.0 and 4.0–5.5, respectively.…”

“…Following administration of the dose, the dynamics of the gastrointestinal tract under fasted state conditions (gastric secretions, gastric emptying, duodenal secretions, and duodenal emptying) were simulated as previously described. 34 To simulate the stomach pH environment of patients with normal gastric acidity, hypochlorhydria, or achlorhydria, the stomach pH was automatically controlled throughout the experiment at values of 1.6, 5.0, and 7.0, respectively. The pH of the duodenum was maintained at 6.5 through active pH control and the addition of duodenal secretions to the duodenal lumen.…”

“…The Diamod (dynamic intestinal absorption MODel) system was applied as this model can simulate several physiologically relevant processes that cannot be captured in simpler in vitro methodologies. 34 This system is a dynamic dissolution model with interconnected online permeation incorporating multiple physiologically relevant processes like gastric and duodenal fluid secretion, fluid composition monitoring, and gastrointestinal transfer kinetics and allowing active pH control in the stomach and duodenal compartment. Hence, Diamod allows the study of the interconnected kinetics of gastrointestinal dissolution, solubility, supersaturation, precipitation, and intestinal permeation processes of oral drugs.…”

“…In the next phase of the development process, the effect of elevated gastric pH conditions was studied using a more advanced full-scale in vitro model that is capable of studying clinically relevant formulations and therefore allows the study of the gastrointestinal performance of optimized drug products. The Diamod (dynamic intestinal absorption MODel) system was applied as this model can simulate several physiologically relevant processes that cannot be captured in simpler in vitro methodologies . This system is a dynamic dissolution model with interconnected online permeation incorporating multiple physiologically relevant processes like gastric and duodenal fluid secretion, fluid composition monitoring, and gastrointestinal transfer kinetics and allowing active pH control in the stomach and duodenal compartment.…”