Is bicarbonate buffer suitable as a dissolution medium?
The objectives of this study were to compare two methods for the preparation of bicarbonate buffer, and to compare media prepared with bicarbonate buffer with commonly used biorelevant and pharmacopoeial media in terms of their suitability for dissolution testing. The various media were compared with regard to ease of preparation, robustness and reproducibility of composition. The dissolution of three formulations of a typical Biopharmaceutical Classification System Class II drug (BIXX) was compared in bicarbonate buffer, standard phosphate buffer, a biorelevant buffer (fasted-state simulating intestinal fluid, FaSSIF) and a modified FaSSIF prepared with bicarbonate buffer. The bicarbonate buffer used for dissolution testing was produced by supplying carbon dioxide to a saline solution (0.9% NaCl, to which 12 or 42 mmol NaOH had been added). The bicarbonate buffer had to be prepared in-situ, which proved to be time-consuming, and the pH stability of the bicarbonate buffer could only be maintained under constant CO2 supply. To minimize the mechanical stress caused by inflow and evaporation of gas, the carbon dioxide was supplied above the medium during the dissolution test. Despite taking these measures, use of bicarbonate buffer led to less reproducible dissolution results than the phosphate buffers commonly used to prepare compendial media and FaSSIF, with coefficient of variance values 1.5- to 5-times higher in bicarbonate buffer. It was concluded that although a bicarbonate buffer system would be physiologically relevant for the fasted state in the small intestine, its suitability for dissolution testing is restricted by lack of practicability and poor reproducibility of results.
Boni
Julia Elisabeth
JE
Pharmaceutical Research & Development, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
Brickl
Rolf Stefan
RS
Dressman
Jennifer
J
D001639:Bicarbonates / Q000737:chemistry*; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000378:metabolism; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D015203:Reproducibility of Results; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013997:Time Factors
D001639:Bicarbonates; D002021:Buffers; D004364:Pharmaceutical Preparations; D010710:Phosphates; D012997:Solvents