TY - JOUR
TI - The impact of reduced gastric acid secretion on dissolution of salts of weak bases in the fasted upper gastrointestinal lumen: Data in biorelevant media and in human aspirates
AU - Litou, C.
AU - Vertzoni, M.
AU - Xu, W.
AU - Kesisoglou, F.
AU - Reppas, C.
JO - European Journal of Pharmaceutics and Biopharmaceutics
PY - 2017
VL - 115
TODO - null
SP - 94-101
PB - Elsevier B.V.
SN - 0939-6411
TODO - 10.1016/j.ejpb.2017.02.009
TODO - base;  bicarbonate;  bile salt;  buffer;  glycocholate sodium;  maleic acid derivative;  oleate sodium;  phosphate;  phosphatidylcholine;  pioglitazone;  taurocholic acid;  inorganic salt, Article;  gastric suction;  human;  human experiment;  in vitro study;  osmolality;  physical chemistry;  simulation;  small intestine;  stomach acid secretion;  stomach juice;  chemistry;  diet restriction;  digestion;  metabolism;  osmolarity;  pH;  physiology;  solubility;  stomach;  stomach acid, Bicarbonates;  Buffers;  Digestion;  Fasting;  Gastric Acid;  Gastrointestinal Contents;  Humans;  Hydrogen-Ion Concentration;  Intestine, Small;  Osmolar Concentration;  Salts;  Solubility;  Stomach
TODO - Purpose To propose media for simulating the intragastric environment under reduced gastric acid secretion in the fasted state at three levels of simulation of the gastric environment and evaluate their usefulness in evaluating the intragastric dissolution of salts of weak bases. To evaluate the importance of bicarbonate buffer in biorelevant in vitro dissolution testing when using Level II biorelevant media simulating the environment in the fasted upper small intestine, regardless of gastric acid secretions. Methods Media for simulating the hypochlorhydric and achlorhydric conditions in stomach were proposed using phosphates, maleates and bicarbonates buffers. The impact of bicarbonates in Level II biorelevant media simulating the environment in upper small intestine was evaluated so that pH and bulk buffer capacity were maintained. Dissolution data were collected using two model compounds, pioglitazone hydrochloride and semifumarate cocrystal of Compound B, and the mini-paddle dissolution apparatus in biorelevant media and in human aspirates. Results Simulated gastric fluids proposed in this study were in line with pH, buffer capacity, pepsin content, total bile salt/lecithin content and osmolality of the fasted stomach under partial and under complete inhibition of gastric acid secretion. Fluids simulating the conditions under partial inhibition of acid secretion were useful in simulating concentrations of both model compounds in gastric aspirates. Bicarbonates in Level III biorelevant gastric media and in Level II biorelevant media simulating the composition in the upper intestinal lumen did not improve simulation of concentrations in human aspirates. Conclusions Level III biorelevant media for simulating the intragastric environment under hypochlorhydric conditions were proposed and their usefulness in the evaluation of concentrations of two model salts of weak bases in gastric aspirates was shown. Level II biorelevant media for simulating the environment in upper intestinal lumen led to underestimation of concentrations in aspirates, even when bicarbonate buffer was used. © 2017 Elsevier B.V.
ER -