DELAYED-RELEASE(ENTERIC-COATED)ARTICLES—GENERAL DRUG RELEASE STANDARD
UseMethod AorMethod Band the apparatus specified in the individual monograph.Conduct theApparatus Suitability Test as directed under Dissolution á711ñ.All test times stated are to be observed within a tolerance of ±2%,unless otherwise specified.
Method A
Procedure (unless otherwise directed in the individual monograph)—
Acid Stage— Place 750mLof 0.1Nhydrochloric acid in the vessel,and assemble the apparatus.Allow the medium to equilibrate to a temperature of 37±0.5.Place 1tablet or 1capsule in the apparatus,cover the vessel,and operate the apparatus for 2hours at the rate specified in the monograph.
After 2hours of operation in 0.1Nhydrochloric acid,withdraw an aliquot of the fluid,and proceed immediately as directed forBuffer Stage.
Perform an analysis of the aliquot using theProcedurespecified in the test forDrug release in the individual monograph.
Unless otherwise specified in the individual monograph,the requirements of this portion of the test are met if the quantities,based on the percentage of the labeled content,of active ingredient dissolved from the units tested conform toAcceptance Table 2.Continue testing through all levels unless the results of both acid and buffer stages conform at an earlier level.
Acceptance Table 2
Level Number Tested Criteria
A1 6 No individual value exceeds 10%dissolved.
A2 6 Average of the 12units (A1+A2)is not more than 10%dissolved,and no individual unit is greater than 25%dissolved.
A3 12 Average of the 24units (A1+A2+A3)is not more than 10%dissolved,and no individual unit is greater than 25%dissolved.
Buffer Stage— [NOTE—Complete the operations of adding the buffer,and adjusting the pHwithin 5minutes.]With the apparatus operating at the rate specified in the monograph,add to the fluid in the vessel 250mLof 0.20Mtribasic sodium phosphate that has been equilibrated to 37±0.5.Adjust,if necessary,with 2Nhydrochloric acid or 2Nsodium hydroxide to a pHof 6.8±0.05.Continue to operate the apparatus for 45minutes,or for the time specified in the individual monograph.At the end of the time period,withdraw an aliquot of the fluid,and perform the analysis using theProcedure specified in the test forDrug releasein the individual monograph.The test may be concluded in a shorter time period than that specified for theBuffer Stage if the requirement for minimum amount dissolved is met at an earlier time.
Interpretation— Unless otherwise specified in the individual monograph,the requirements are met if the quantities of active ingredient dissolved from the units tested conform toAcceptance Table 3.Continue testing through the three levels unless the results of both stages conform at an earlier level.The value ofQinAcceptance Table 3is 75%dissolved unless otherwise specified in the individual monograph.The quantity,Q,specified in the individual monograph,is the total amount of active ingredient dissolved in both the acid and buffer stages,expressed as a percentage of the labeled content.The 5%and 15%values in Acceptance Table 3are percentages of the labeled content so that these values andQare in the same terms.
Acceptance Table 3
Level Number Tested Criteria
B1 6 Each unit is not less than Q+5%.
B2 6 Average of 12units (B1+B2)is equal to or greater than Q,and no unit is less than Q-15%.
B3 12 Average of 24units (B1+B2+B3)is equal to or greater than Q,not more than 2units are less than Q-15%,and no unit is less than Q-25%.
Method B
Procedure (unless otherwise directed in the individual monograph)—
Acid Stage— Place 1000mLof 0.1Nhydrochloric acid in the vessel,and assemble the apparatus.Allow the medium to equilibrate to a temperature of 37±0.5.Place 1tablet or 1capsule in the apparatus,cover the vessel,and operate the apparatus for 2hours at the rate specified in the monograph.After 2hours of operation in 0.1Nhydrochloric acid,withdraw an aliquot of the fluid,and proceed immediately as directed underBuffer Stage.
Perform an analysis of the aliquot using theProcedurespecified in the test forDrug release in the individual monograph.
Unless otherwise specified in the individual monograph,the requirements of this portion of the test are met if the quantities,based on the percentage of the labeled content,of active ingredient dissolved from the units tested conform toAcceptance Table 2underMethod A.Continue testing through all levels unless the results of both acid and buffer stages conform at an earlier level.
Buffer Stage— [NOTE—For this stage of the procedure,use buffer that previously has been equilibrated to a temperature of 37±0.5.]Drain the acid from the vessel,and add to the vessel 1000mLof pH6.8phosphate buffer,prepared by mixing 0.1Nhydrochloric acid with 0.20Mtribasic sodium phosphate (3:1)and adjusting,if necessary,with 2Nhydrochloric acid or 2Nsodium hydroxide to a pHof 6.8±0.05.[NOTE—This may be accomplished also by removing from the apparatus the vessel containing the acid and replacing it with another vessel containing the buffer and transferring the dosage unit to the vessel containing the buffer.]Continue to operate the apparatus for 45minutes,or for the time specified in the individual monograph.At the end of the time period,withdraw an aliquot of the fluid,and perform the analysis using theProcedure specified in the test forDrug release in the individual monograph.The test may be concluded in a shorter time period than that specified for theBuffer Stage if the requirement for minimum amount dissolved is met at an earlier time.
Interpretation— Proceed as directed forInterpretation underMethod A.
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