Dissolved Oxygen as a Measure for De- and Reaeration of Aqueous Media for Dissolution Testing

Abstract

In order to obtain ,"eliable find reproducible ,"esults fr01Il dissolution test" it is often neL"essmy to det,,,"ate tbe dissolutioll ?IIedium. 111 tbe Cl/./"rem work, four diff,,"ellt ?IIetbods of degassing tbe medium 7V,,"e compared by mel/r/wing tbe COI/centrotion of oxygen in tbe ?IIedimll before mllil/fter tbe del/emtiol1 p,wed"re. The oxygen concmtratioll was deW"mined "nd,," deftned conditions by using fin o;rygen senso," iiI/sed on a Clm'k electrode" The metbod des{,"ibed ill the USP 23 (beating to 4 5"C pIllS fillnltiol1) I/cbieved an 85% ±ll % ,"edllction in tbe oxygen concentrotion" /-Ieating to 100"C m7t1ted in a ,-eduction of only 50% ±3%, while filtl"lltion ,"edllced tbe oxyg'" cOl1tmt by 65% ±4%. A ?IIetbod developed il1 our laboratm) combinil1g ultrasound and application ofa vacuum achieved fI 95% ±2% ,.ed",1ion. Aft,,• degassing, tbe medill/II must 1HllIdly be u"amiCl-red to tbe dissoltttion vessels before tbe test is mn. Tbe ,"esults indiatt-ed that even careft" filling remlted in a 37% iucrease in the oxygen content, while typical filling proced","es ,"emlted ill an almost tbree-fold increase. It was furth,,' shmv11 tbat tbe medi-Il1Il gmdually becmlles ,"e-saturated dl/ring tbe dissolntiou test itself, at amte that is dependem on tbe apparatlls (basket vet"-S/lS paddle) and the rotational speed. 120 minutes into tbe test, tbe o:cygen COl1celm"fltion was alna(1y 60% oftbe satamtion value" Conclusions; Tbe "least"-e,,,ent of o.rygen was de'lllon-SI1"flted to be a ,"eproducible and dil-ect metbod for mearll1"ing tbe efficienry of deaemtion. It was ftt/1ber sbown thflt the efficiency of dea"wion is bigbly depC1ldC1lt on tbe metbod /lsed, and tbllt "e-introduction of ail" into tbe medium occan not only duringfilling of tbe dissolution vessels but also d","ing tbe dissolution test.

Technical Note: Total Dissolved Gas Pressure (TDGP) Sensing in the Laboratory

“…This proceeds from the need to avoid bubble formation when the water is heated or subjected to lowstrength ultrasonic fields. The use of a simple oxygen sensor (2,3) to provide an estimate of the degree to which distilled water has been degassed can introduce inconsistent results due to different distillation methods,height above sea level,and conditions and duration of storage. As shown by Eaton et al (4),the degree of deaeration and procedures used to affect it can be a major contributor to such errors in currently used apparatus.…”

Evaluation of the Sensitivity of USP Prednisone Tablets to Dissolved Gas in the Dissolution Medium Using USP Apparatus 2

“…The presence of dissolved gases also is suspected,in many cases,of failure to meet apparatus suitability standards (2,5). * Previous studies have demonstrated the use of dissolved oxygen as a measure of deaeration (7)(8)(9)(10),although some indicate that dissolved oxygen alone is not an adequate measure (11) with recommendations that other gases,particularly nitrogen and carbon dioxide, should be measured and controlled as well. In this study, oxygen as well as the total dissolved gas pressure (the sum of the partial pressures of oxygen,nitrogen,argon,carbon dioxide,and other trace gases) was monitored from the time the medium was transferred into the dissolution vessel until the end of the dissolution test.…”

Effects of Deaeration Methods on Dissolution Testing in Aqueous Media: A Study Using a Total Dissolved Gas Pressure Meter**Opinions expressed in this report are those of the authors and do not necessarily reflect the views or policies of the FDA.

“…For the past 20 years, scientists have evaluated different deaeration techniques that utilize vacuum, heating, sonication, membrane filtration, equilibration at 37°C overnight, helium sparging, etc 3–7. These methods demonstrate various degrees of effectiveness and, to compare deaeration methods, several authors have investigated the use of oxygen meters to determine if the medium has been degassed sufficiently 8–11. In these studies, the oxygen content was taken to represent the amount of air dissolved in the dissolution medium.…”