NOTICE AND WARNING
`
`Concerning US. Parent or Trademark Rights
`
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`other person may exercise the same without express permission, authority, or license secured
`from such patent or trademark owner.
`
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`Attention is called to the fact that USP and NF text is fully copyrighted. Authors and others
`wishing to use portions of the text should request permission to do so from the Secretary of the’
`USPC Board of Trustees.
`
`The United States Pharmacopeial Convention, inc.
`© 1999
`12601 Twinbrook Parkway, Rockville, MD 20852.
`All rights reserved
`ISSN 0195-7996
`ISBN I-889788-03-1
`
`Printed by National Publishing, Philadelphia, PA
`
`

`
`€553’? Ed
`
`§ELA¥ED~REi,£EASE {ENTEREC-CGATED}
`A.R’i‘ICLES--GENERAL DRUG R£LEASE
`STANDARD
`
`or Method B and the apparatus specified in the
`Use lvlarfzozz‘
`individual monograph. Conduct the Apparatus Szzitobiliry “fast as
`directed under ifissolurion (Till). Ali
`test times stated are to be
`observed within a tolerance of :“?%. unless. otherwise specified.
`
`Method A
`
`{unless
`
`otherwise
`
`directed
`
`in
`
`the
`
`individual
`
`Procedure
`monograph)-»
`hydrochloric acid in the
`Acid srage-Place 75% mL of 0.1
`vessel, and assemble the apparatus, Allow the medium to equilibrate
`to a temperature of 37 i 05°. Place i tablet or 3 capsule in the
`apparatus, cover the vessel, and operate the apparatus for 2 hours
`at the rate specified in the monograph.
`After 2 hours of operation in ().l N hydrochloric acid, withdraw
`an aliquot of the fluid, and proceed immediately as directed under
`Bzgjfer stage,
`Perform an analysis of the aliquot using the Procedure specified
`in the test for Drug release in the individual monograph.
`Unless otherwise specified in the individual monograph, the re-
`quirements of this portion of the test are met if the quantities, based
`on the percentage of the labeled content, of active ingredient dis-
`solved from the units tested conform to Acceptance Table 2. Con-
`tinue testing through all levels unless the results of both acid and
`buffer stages conform at an earlier level.
`
`Eiiyst-:*rz§ Eests § C2224} Qrttg Reiease
`
`l§4?
`
`
`
`Acceptance Table 3
`Number
`
`Levei
`8,
`B2
`
`Tested
`d
`6
`
`E,
`
`E2
`
`Criteria
`7
`Each unit is not less than Q + 5%.
`Average of E2 units (8, + B2) is equal
`to or greater than
`and no unit is less
`than Q ~ l5%,
`Average of 24 units (B, + B, + B3) is
`equal to or greater than Q, not more
`than 2 units are less than Q -— 15%,
`and no unit is less than Q ~ 25%.
`
`Acid stage-~—PlaCe 1000 ml, of 0.1 N hydrochloric acid in the
`vessel, and assemble the apparatus. Allow the medium to equilibrate
`to a temperature of 37 : 05°. Place 1
`tablet or l capsule in the
`apparatus, cover the vessel, and operate the apparatus for 2 hours
`at the rate specified in the monograph. After 2 hours of operation
`in 0.1 N hydrochloric acid, withdraw an aliquot of the fluid, and
`proceed immediately as directed under Bufler stage,
`Perform an analysis of the aliquot using the Procedure specified
`in the test for Drug release in the individual monograph.
`Unless otherwise specified in the individual monograph, the re-
`quirements of this portion of the test are met if the quantities, based
`on the percentage of the labeled content, of active ingredient dis-
`solved from the units tested conform to Acceptance Table 2 under
`Method A. Continue testing through all levels unless the results of
`both acid and buffer stages conform at an earlier level.
`
`Bufier Stage——[NOTE——FOr this stage of the procedure, use buffer
`that previously has been equilibrated to a temperature of 37 :
`().5‘’.] Drain the acid from the vessel, and add to the vessel 1000
`mL of pH 6.8 phosphate buffer, prepared by mixing 0.1 N hydro-
`chloric acid with 0.20 M tribasic sodium phosphate (3:1) and ad-
`justing, if necessary, with 2 N hydrochloric acid or 2 N sodium
`hydroxide to a pH of 6.8 2*: 0.05. {NOTE-—-Tl’1lS may be accom-
`plished 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 45 minutes, or for the time
`specified in the individual monograph. At the end of the time pe-
`riod, withdraw an aliquot of the fluid, and perform the analysis
`using the Procedure specified in the test for Drug release in the
`individual monograph. The test may be concluded in a shorter time
`period than that specified for the Bufler stage if the requirement for
`minimum amount dissolved is met at an earlier time.
`
`Interpretation—Proceed as directed for Interpretation under
`Method A.
`
`TILANSDERMAL DELIVERY SYSTEMS——
`GENERAL DRUG RELEASE STANDARDS
`
`Apparatus
`
`(Paddle over Disk)
`
`Apparatus—-Use the paddle and vessel assembly from Appara-
`ms 2 as described under Dissolution (711), with the addition of a
`stainless steel disk assembly‘ designed for holding the transdermal
`system at the bottom of the vessel. Other appropriate devices may
`be used, provided they do not sorb, react with, or interfere with the
`specimen being tested? The temperature is maintained at 32 1- 05°.
`A distance of 25 1- 2 mm between the paddle blade and the surface
`of the disk assembly is maintained during the test. The vessel may
`be covered during the test to minimize evaporation. The disk as-
`sembly for holding the transdermal system is designed to minimize
`any “dead" volume between the disk assembly and the bottom of
`the vessel. The disk assembly holds the system flat and is positioned
`such that the release surface is parallel with the bottom of the paddle
`blade (see Figure 4).
`
`Level
`A,
`
`A3
`
`A,
`
`Acceptance Table 2
`Number
`Tested
`6
`
`Criteria
`No individual value exceeds l0% dis-
`solved.
`
`6
`
`l2
`
`Average of the l2 units (A, + AZ) is not
`more than l0% dissolved, and no in-
`dividual unit
`is greater
`than 25%
`dissolved.
`
`Average of the 24 units (A, + A2 + A3)
`is not more than 10% dissolved, and
`no individual unit is greater than 25%
`dissolved.
`
`Bufler stage-—[NOTE—-Complete the operations of adding the
`buffer. and adjusting the pH within 5 minutes] With the apparatus
`operating at the rate specified in the monograph, add to the fluid in
`the vessel 250 ml, of 0,20 M tribasic sodium phosphate that has
`been equilibrated to 37 1" 05°. Adjust, if necessary, with 2 N hy-
`drochloric acid or 2 N sodium hydroxide to a pH of 6,8 : 0,05.
`Continue to operate the apparatus for 45 minutes. or for the time
`specified in the individual monograph, At the end of the time pe-
`riod. withdraw an aliquot of the fiuid, and perform the analysis
`using the Procedure specified in the test for Drug release in the
`individual monograph. The test may be concluded in a shorter time
`period than that specified for the Buffer stage if the requirement for
`minimum amount dissolved is met at an earlier times
`Interpretation»-Unless otherwise specified in the individual
`monograph, the requirements are met if the quantities of active in-
`gredient dissolved from the units tested conform to Acceptance Ta-
`ble 3. Continue testing through the three levels unless the results
`of both stages conform at an earlier level. The value of Q in Ac-
`ceptance Table 3 is 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 l5% values in Acceptance Table 3 are
`percentages of the labeled content so that these values and Q are
`in the same terms.
`
`
`
`Method B
`
`Procedure (unless otherwise directed in the individual mono-
`staph)-
`
`‘ Disk assembly (stainless support disk) may be obtained from
`Millipore Corp, Ashley Rd, Bedford, MA 01730.
`3 A suitable device is the watchglass-patch-polytef mesh sand-
`wich assembly available as the Transdermal Sandwich“ from Han-
`son Research Corp.. 9810 Variel Ave, Chatsworth, CA 91311.
`
`..__ _
`
`,