Measurement of Dissolved Oxygen as a Determination of Media Equilibrium During Dissolution Testing

Abstract

Introduction The scientific community has accepted that dissolved air in dissolution media can affect the dissolution rate of solid dose units. Several methods have been developed to accomplish deaeration, but the industry standard has been the USP method, using heat, vacuum and filtering (1). Alternate methods of deaeration were declared comparable to the USP method by virtue of 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, while indicating apparatus suitability, did not measure to any degree the actual amount of dissolved air present. Oxygen, being approximately 20% of air, was easily measured using available dissolved oxygen meters. The measurement of dissolved oxygen allowed a quantitative means to confirm comparability to USPdeaerated media. The use of some deaeration techniques may actually deaerate dissolution media to too low a level. It has been theorized that deaeration to too low a level, such as by vacuum/sonication deaeration, may actually create a disturbance during the dissolution process (2). Dissolved air in dissolution media adjusted to achieve equilibrium. Media with low levels of dissolved air absorbed air until equilibrium was achieved. Conversely, saturated media released dissolved air, until equilibrium was achieved. Since deaeration is basically the removal of dissolved air in the media, it seemed most appropriate to measure a major component of that dissolved air. Dissolved oxygen has long been measured in the waste water treatment industry, and several portable oxygen meters were available, with demonstrated ease of use and reliability in reproducing results. The level of dissolved oxygen, which could be measured, was a direct relation to the amount of dissolved air, or deaeration of the dissolution media. This provided a measurable means of comparing methods of deaeration to the USP method. In addition, the amount of deaeration and time required to achieve the optimal level of deaeration were also determined for each method in use. The objectives of this project were to develop a means of accurately measuring the deaeration of 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.