At Level III of biorelevant media simulation, a comprehensive replication of the gastrointestinal (GI) tract environment includes factors such as luminal osmolality, pH range, buffer capacity using specific buffer ingredients, bile components, dietary lipid components, dietary proteins, increased viscosity (notably in the fed stomach and lower intestine), and the replication of digestive processes in the upper GI tract.
This simulation primarily emulates conditions found in the fed state, but there are instances where certain active pharmaceutical ingredients (APIs), such as peptides prone to luminal degradation, and specific lipid-based formulations might experience some degree of digestion during the fasted state.
The augmented viscosity and digestion within the fed stomach have a notable impact on the performance of oral dosage forms. This viscosity enhancement is emulated using substances like pectin and hydroxypropyl cellulose. Elevated stomach viscosity is particularly vital for the absorption of drugs with limited permeability, especially those absorbed in the upper intestine. The inclusion of dietary proteins and lipids is vital for accurately simulating intragastric digestion in the fed state. However, it remains a challenge to identify suitable proteins for in-vitro experiments due to insufficient luminal data.
Simulating digestion within the fasted stomach is complex due to the brief gastric residence time and the limited activity of gastric lipase under highly acidic pH levels. Nevertheless, the addition of pepsin to simulations can yield physiologically relevant surface tension, which is significant when addressing wetting-related concerns in the fasted stomach.
Several in-vitro techniques have been employed to replicate fed stomach digestion. Some approaches involve mimicking actual meals used in in-vivo studies while accounting for stomach motility patterns. Other methods utilize ultra-high temperature treated milk to replicate the presence of dietary proteins and lipids. In the small intestine, various simulation methods exist, including the use of pancreatin extract or lipid formulations combined with specific buffers containing chemicals like Tris-maleate buffer, CaCl2, NaCl, sodium taurodeoxycholate, and phosphatidylcholine.
Dosage form behavior varies throughout different segments of the GI tract. Monolithic non-disintegrating dosage forms, particularly those with modified-release properties, require evaluation during their residence in the fasted stomach. The dosage form’s size dictates its passage through the GI tract and exposure to varying volumes of media. Additionally, simulating bacterial degradation and solid food remnants in the lower intestine is an ongoing area of investigation.
Level III biorelevant media play a crucial role in assessing lipid-based formulations, luminal stability characteristics of APIs, and dosage forms.
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Resource Person: Prakash Amate