Measurement of dissolved oxygen as a determination of media equilibrium during dissolution testing

Abstract

Scientists have known for years that deaeration of aqueous dissolution media can affect the dissolution rate of solid dosage forms. Several methods have been developed to accomplish deaeration,but the industry standard has been the USP method,using heat,vacuum and filtering. Alternate methods of deaeration may be considered comparable to the USP method by passing the USP Apparatus Suitability Tests,using USP Prednisone and Salicylic Acid calibrator tablets. Closer examination of this procedure,however,indicated that additional tests of deaeration levels were warranted.The USP Apparatus Suitability Tests do not measure to any degree the actual amount of dissolved air present. The use of some techniques may actually deaerate dissolution media to too low a level.Media with low levels of dissolved air absorbed air,and saturated media released dissolved air,until equilibrium was achieved. It was shown that dissolved air in dissolution media adjusted to achieve equilibrium. Acceptable results for the Apparatus Suitability Tests should be combined with measurement of the dissolved oxygen to assure that dissolution testing is conducted on a consistent basis. Through experiments, it was established that a level of dissolved oxygen within a range of 4 – 7 mg/L produced an equilibrium effect in regard to dissolved air in the media,such that no appreciable change occurred during the dissolution process. USP-equivalent media should only be produced by a means that results in near equilibrium of both temperature & dissolved air.