Physiological bicarbonate buffers: stabilisation and use as dissolution media for modified release systems

An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

“…Other ions and luminal constituents, such as bile salts, proteins, carbohydrates, and other food components also contribute to the final buffer capacity and the pH (3)(4)(5)(6). However, as they play a minor role, the bicarbonate buffer is considered being the most biorelevant buffer system for the simulation of intestinal conditions (7,8). The carbonate buffer also reflects the ionic composition and the buffer capacity of small intestinal fluids (7).…”

“…Furthermore, it has been shown that bicarbonate buffers are more discriminative than compendial phosphate buffers and allow a better estimation of drug release from pH responsive formulations such as coated dosage forms intended to release the drug in the ileocecal region. It has also been demonstrated that bicarbonate buffers media enable a better prediction of in vivo disintegration times and drug release from products containing ionizable compounds (4,7,8,(12)(13)(14)(15).…”

“…If at all, Krebs buffer and Hanks buffer as well as modifications thereof are typically used as bicarbonate-buffered media (7,8). However, due to the thermodynamic instability of these solutions containing bicarbonate ions and carbonic acid, unpredictable pH rises due to the loss of CO 2 from the solution occur over time.…”

“…However, due to the thermodynamic instability of these solutions containing bicarbonate ions and carbonic acid, unpredictable pH rises due to the loss of CO 2 from the solution occur over time. Carbonic acid is a weak acid (pK a ∼6.4), which is spontaneously formed by the dissolution of its anhydride, i.e., carbon dioxide (CO 2 ) in water (8,16). The pH of aqueous solutions of CO 2 ranges from pH 3.9 to 6.97 and is dependent on the partial pressure of CO 2 and the temperature of the fluid.…”

“…CO 2 loss can be minimized by the use of seal devices for dissolution testers or by covering aqueous dissolution media with organic layers such as paraffin to prevent degassing of carbonate-based dissolution media during the experiment (8). The pH can also be maintained by replacing the escaped CO 2 via feeding an equal amount of CO 2 (gas) into the solution.…”