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

Abstract

Abstract. The bicarbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions. However, its use in dissolution testing of solid oral dosage forms is very limited. The reason for this is the thermodynamic instability of the solution containing hydrogen carbonate ions and carbonic acid. The spontaneous loss of carbon dioxide (CO 2 ) from the solution results in an uncontrolled increase of the pH. In order to maintain the pH on the desired level, either a CO 2 loss must be completely avoided or the escaped CO 2 has to be replaced by quantitative substitution, i.e. feeding the solution with the respective amount of gas, which re-acidifies the buffer after dissociation. The present work aimed at the development of a device enabling an automatic pH monitoring and regulation of hydrogen carbonate buffers during dissolution tests.

Dissolution of mesalazine modified release tablets under standard and bio-relevant test conditions

“…This medium was replaced by Hanks hydrogen carbonate buffer (pH 6.8) with 0.1 % Tween 80 after 2 h to simulate the pH and the surface tension of fasted state intestinal conditions [33]. The pH value of the bicarbonate buffer was continuously adjusted with an accuracy of ± 0.02 pH units by using the pHysio‐stat system [26]…”

“…[33] The pH value of the bicarbonate buffer was continuously adjusted with an accuracy of ± 0.02 pH units by using the pHysio-stat system. [26]…”

“…The intestinal intraluminal fluids are buffered mainly by hydrogen carbonate ions (HCO 3 − ), as the most bio‐relevant buffer system. Furthermore, they are an integral part of the ionic composition of the small intestinal fluids [26,27]. Thus, the use of the hydrogen carbonate buffers is essential for a realistic simulation of intestinal conditions in terms of a reasonable estimation of the drug release from MR solid oral dosage forms containing ionisable drugs or excipients [22,24,27,28]…”

“…Furthermore, they are an integral part of the ionic composition of the small intestinal fluids. [26,27] Thus, the use of the hydrogen carbonate buffers is essential for a realistic simulation of intestinal conditions in terms of a reasonable estimation of the drug release from MR solid oral dosage forms containing ionisable drugs or excipients. [22,24,27,28] It is known that the release behaviour of targeted MR formulations in the GIT can also be affected by mechanical stress.…”

Physicochemical Properties of Buffers Used in Simulated Biological Fluids with Potential Application for In Vitro Dissolution Testing: A Mini-review

“…One method of increasing buffer capacity is to increase buffer concentration; however, this approach may be inconsistent with the physicochemical properties of the simulated biological fluid. Garbacz et al (56) reported on the use of an automated pH-stat system for monitoring and regulating the pH of bicarbonate buffers; however, the use of a pH-stat adds complexity and requires optimizing additional experimental parameters (57).…”