Background

Hydrogen carbonate is the most biorelevant buffer system for the simulation of intestinal conditions. However, its use for the in vitro evaluation of the dissolution performance of solid oral dosage forms is limited. This is mostly due to its thermodynamic instability resulting in an uncontrolled CO2 loss followed by pH increase. In order to maintain the pH value, it is inevitable to replace the escaping CO2 by introducing equivalent gas volumes into the solution to re-acidify the buffer system. For this purpose we developed a novel device, the pHysio-stat® which enables adjustment and monitoring of hydrogen carbonate buffers during dissolution testing.

pHysio-stat®

The pHysio-stat® is an automated device represented by a novel microprocessor-driven system which enables the adjustment of the media pH in a single dissolution vessel. The pHysio-stat® is composed of a pH electrode, a gas diffusor, a digital microcontroller and a proportional valve. The device is driven by a custom-made software which controls the pH adjustment in the range of pH 5.5 to 9.0 and enables the setting of trigger values as well as a regulation hysteresis within the pharmacopoeial tolerance range of ± 0.05 pH. The pH electrode and the gas diffusor remain immersed in the dissolution medium and the potential of the electrode is measured and digitalized over the entire dissolution experiment. The digital signal is then processed to be instantly applicable for the regulation of the proportional valve which adjusts the amount of CO2 that is introduced into the dissolution medium via the diffusor.

The pHysio-stat® device:

  • can precisely monitor and adjust the pH value of commonly used hydrogen carbonate buffers such as Hanks and Krebs buffer solutions and modifications of biorelevant media
  • enables a precise pH adjustment in the range of pH 5.5 to 9.0 with a maximum deviation of ± 0.05 pH units
  • utilizes pure CO2 as well as mixtures of CO2 with other gases as a titer
  • is characterized by sufficient robustness, good performance stability as well as a highly dynamic pH adjustment
  • can be used in various pharmacopoeial and non-compendial dissolution test devices.

These unique features make the pHysio-stat® particularly useful for routine applications in dissolution tests in which hydrogen carbonate based buffers are utilized.

 

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