2000
`
`USP 24
`NF 19
`
`THE UNITED STATES PHARMACOPEIA
`
`THE NATIONAL FORMULARY
`
`By authority of the United States Pharmacopeial
`Convention, Inc., meeting at Washington, D.C.,
`March 9-12, 1995. Prepared by the Committee of
`Revision and published by the Board of Trustees
`
`Official from January 1, 2000
`
`UNITED STATES PHARMACOPEIAL CONVENTION, INC.
`12601 Twinbrook Parkway, Rockville, MD 20852
`
`

`

`NOTICE AND WARNING
`NOTICE AND WARNING
`
`Concerning U.S. Patent or Trademark Rights
`Concerning U.S. Patent or Trademark Rights
`
`The inclusion in the Pharmacopeia or in the National Formulary of a monograph on any drug in
`The inclusion in the Pharmacopeia or in the National Formulary of a monograph on any drug in
`respect to which patent or trademark rights may exist shall not be deemed, and is not intended
`respect to which patent or trademark rights may exist shall not be deemed, and is not intended
`as, a grant of, or authority to exercise, any right or privilege protected by such patent or
`as, a grant of, or authority to exercise, any right or privilege protected by such patent or
`trademark. All such rights and privileges are vested in the patent or trademark owner, and no
`trademark. All such rights and privileges are vested in the patent or trademark owner, and no
`other person may exercise the same without express permission, authority, or license secured
`other person may exercise the same without express permission, authority, or license secured
`from such patent or trademark owner.
`from such patent or trademark owner.
`
`Concerning Use of USP or NF Text
`Concerning Use of USP or NF Text
`Attention is called to the fact that USP and NF text is fully copyrighted. Authors and others
`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
`wishing to use portions of the text should request permission to do so from the Secretary of the
`USPC Board of Trustees.
`USPC Board of Trustees.
`
`-~
`The United States Pharmacopeial Convention, Inc.
`© 1999
`The United States Pharmacopeial Convention, Inc.
`© 1999
`12601 Twinbrook Parkway, Rockville, MD 20852.
`12601 Twinbrook Parkway, Rockville, MD 20852.
`All rights reserved
`All rights reserved
`ISSN 0 195-7996
`ISSN 0195-7996
`ISBN 1-889788-03-1
`ISBN 1-889788-03-1
`
`Printed by National Publishing, Philadelphia, PA
`Printed by National Publishing, Philadelphia, PA
`
`

`

`Contents
`Contents
`
`0
`;) ueu
`
`Notices
`Notices
`
`General Notices and
`General Notices and
`Requirements ....................... .
`Requirements
`
`
`1
`
`Monographs Official Monographs for
`Monographs Official Monographs for
`
`USP 24
`USP 24 ............................. ..
`
`15
`15
`
`vii
`vii
`vii
`vii
`vii
`vii
`ix
`ix
`
`ix
`ix
`
`ix
`ix
`
`X
`
`USP 24
`USP 24
`
`People
`People
`
`Preamble
`Preamble
`
`........... .
`Officers of the Convention
`
`Officers of the Convention
`
`Board of Trustees ...................... .
`Board of Trustees
`
`
`General Committee of Revision
`..... .
`General Committee of Revision
`
`
`Executive Committee of Revision ... .
`Executive Committee of Revision
`
`USP Nomenclature
`USP Nomenclature
`Committee .......................... .
`Committee
`
`Division of Standards Development
`Division of Standards Development
`Executive Committee and
`Executive Committee and
`
`Subcommittees
`Subcommittees ..................... .
`USP Reference Standards
`USP Reference Standards
`Committee .......................... .
`Committee
`USP—FDA Joint Committee on
`USP-FDA Joint Committee on
`Bioequivalence
`Bioequivalence ..................... .
`USP-FDA Antibiotic Monograph
`USP—FDA Antibiotic Monograph
`Subcommittee ...................... .
`Subcommittee
`Division of Standards Development
`Division of Standards Development
`Panels
`............................... .
`Panels
`
`Division of Information Development
`Division of Information Development
`Executive Committee ............ ..
`Executive Committee
`
`Division of Information Development
`Division of Information Development
`Advisory Panels
`.................. ..
`
`
`Advisory Panels
`Collaborators During 1995-2000 .... .
`Collaborators During 1995-2000
`
`Members of the United States
`Members of the United States
`Pharmacopeial Convention
`Pharmacopeial Convention
`
`...... .
`
`
`
`X
`
`General
`x General
`Chapters
`Chapters
`
`X
`
`X
`
`xi
`xi
`
`xi
`xi
`xvi
`xvi
`
`xx
`xx
`
`Reagents
`Reagents
`
`xxvi
`Articles of Incorporation .............. .
`xxvi
`Articles of Incorporation
`
`
`Constitution and Bylaws .............. .
`Constitution and Bylaws
`xxvii
`xxvii
`
`xxxvii
`Rules and Procedures .................. .
`Rules and Procedures
` xxxvii
`USPC Communications Policy ........ .
`USPC Communications Policy
`
`xliii
`xliii
`USPC Document Disclosure
`USPC Document Disclosure
`
`Policy
`Policy ................................ .
`Proceedings .............................. .
`Proceedings
`
`History of the Pharmacopeia of the
`History of the Pharmacopeia of the
`United States ...................... ..
`
`United States
`Preface to USP 24 .................... ..
`Preface to USP 24
`
`
`
`xliv
`xliv
`xlvi
`xlvi
`
`1
`!xiii
`lxiii
`
`Admissions Articles Admitted to USP by
`Admissions Articles Admitted to USP by
`Supplement ......................... .
`Supplement
`Official Titles Changed by
`Official Titles Changed by
`Supplement ......................... .
`Supplement
`
`Changes in Official Titles ............. .
`Changes in Official Titles
`
`Revisions Appearing in USP 24 That
`Revisions Appearing in USP 24 That
`Were Not Included in USP 23
`Were Not Included in USP 23
`Including Supplements ........... .
`Including Supplements
`
`
`Articles Included in USP 23 but Not
`Articles Included in USP 23 but Not
`Included in USP 24
`
`Included in USP 24 .............. ..
`
`!iii
`liii Tables
`Tables
`!vi
`lvi
`!ix
`lix
`
`lix
`!ix
`
`lix
`!ix
`
`see page 1773 for detailed contents
`see page 1773 for detailed contents
`General Tests and Assays ............. .
`General Tests and Assays
`General Requirements for Tests and
`General Requirements for Tests and
`Assays
`Assays .............................. ..
`Apparatus for Tests
`Apparatus for Tests
`and Assays
`
`and Assays
`......................... .
`Microbiological Tests
`Microbiological Tests ............... .
`Biological Tests and Assays ....... .
`Biological Tests and Assays
`Chemical Tests and Assays ....... ..
`Chemical Tests and Assays
`Physical Tests and
`Physical Tests and
`Determinations
`Determinations ..................... .
`General Information
`General Information .................... .
`
`1775
`1775
`
`1775
`1775
`
`1801
`1801
`1809
`1809
`1823
`1823
`1853
`1853
`
`1895
`1895
`2008
`2008
`
`................................. .
`Reagents
`
`Reagents
`
`Indicators and Indicator Test
`Indicators and Indicator Test
`
`Papers
`
`Papers
`............................... .
`Solutions ................................. .
`Solutions
`
`Buffer Solutions
`
`
`Buffer Solutions .................... ..
`Colorimetric Solutions
`Colorimetric Solutions .............. .
`
`Test Solutions ....................... ..
`Test Solutions
`
`Volumetric Solutions
`................ '
`Volumetric Solutions
`
`
`
`2116
`2116
`
`2229
`2229
`2231
`2231
`2231
`2231
`2232
`2232
`2232
`2232
`2240
`2240
`
`Containers for Dispensing Capsules
`Containers for Dispensing Capsules
`and Tablets ......................... .
`
`and Tablets
`Description and Relative Solubility of
`Description and Relative Solubility of
`USP and NF Articles ............. .
`USP and NF Articles
`
`Approximate Solubilities of USP and
`Approximate Solubilities of USP and
`NF Articles
`NF Articles ......................... .
`Atomic Weights
`
`Atomic Weights
`....................... ..
`Alcoholometric Table .................. .
`Alcoholometric Table
`Thermometric Equivalents ............ .
`Thermometric Equivalents
`
`2248
`2248
`
`2254
`2254
`
`2299
`2299
`2305
`2305
`2308
`2308
`2311
`2311
`
`iii
`111
`
`

`

`iv
`IV
`
`Contents
`Contents
`
`NUTRITIONAL
`NUTRITIONAL
`SUPPLEMENTS
`SUPPLEMENTS
`
`Monographs Official Monographs ....................
`Monographs Official Monographs
`
`2312
`2312
`
`General
`General
`Chapters
`Chapters
`
`see page 2381 for detailed contents
`see page 2381 for detailed contents
`General Tests and Assays ..............
`
`General Tests and Assays
`
`2382
`2382
`
`NF 19
`NF 19
`
`People
`People
`
`See USP 24, page vii
`See USP 24, page vii
`
`Preamble
`Preamble
`
`Preface to NF 19 .........................
`Preface to NF 19
`
`2400
`2400
`
`Admissions Articles Official in NF 18 ..............
`Admissions Articles Official in NF 18
`
`2402
`2402
`
`USP 24-NF 18
`USP 24-NF 18
`
`Tables
`Tables
`
`USP and NF Excipients
`USP and NF Excipients
`Ingredients, Listed by Categories
`Ingredients, Listed by Categories
`
`
`
`2404
`2404
`
`Notices
`Notices
`
`General Notices and
`General Notices and
`Requirements ........................
`Requirements
`
`2407
`2407
`
`Monographs official Monographs for NF 19 .......
`Monographs Official Monographs for NF 19
`
`2408
`2408
`
`General
`General
`
`see page 1773 for detailed contents
`see page 1773 for detailed contents
`General Tests and Assays See
`General Tests and Assays See
`USP 24, page 1775
`USP 24, page 1775
`General Information See USP 24,
`General Information See USP 24,
`page 2008
`page 2008
`
`Reagents
`Reagents
`
`Reagents See USP 24, page 2116
`Reagents See USP 24, page 2116
`Indicators and Indicator Test
`Indicators and Indicator Test
`Papers See USP 24, page 2229
`Papers See USP 24, page 2229
`Solutions See USP 24, page 2231
`Solutions See USP 24, page 2231
`
`Index
`Index
`
`Combined Index to USP 24 and
`Combined Index to USP 24 and
`NF 19
`
`NF 19 .................................
`
`2541
`2541
`
`

`

`USP 24
`USP 24
`
`Physical Tests I (711) Dissolution
`Physical Tests I (711) Dissolution
`
`1941
`1941
`
`given in the manufacturer's operating instructions. If the sample
`given in the manufacturer's operating instructions. If the sample
`must be degassed under vacuum, follow the recommendations in
`must be degassed under vacuum, follow the recommendations in
`the individual monographs and the instructions in the operating
`the individual monographs and the instructions in the operating
`manual for the pycnometer.
`manual for the pycnometer.
`The measurement sequence above describes the procedure for the
`The measurement sequence above describes the procedure for the
`gas pycnometer shown in Figure 1. If the pycnometer differs in
`gas pycnometer shown in Figure 1. If the pycnometer differs in
`operation or in construction from the one shown in Figure 1, follow
`operation or in construction from the one shown in Figure 1, follow
`the operating procedure given in the manual for the pycnometer.
`the operating procedure given in the manual fof the pycnometer.
`Repeat the measurement sequence for the same powder sample
`Repeat the measurement sequence for the same powder sample
`until consecutive measurements of the sample volume, V,, agree to
`agree to
`until consecutive measurements of the sample volume,
`within 0.2%. Unload the test cell and measure the final powder
`within 0.2%. Unload the test cell and measure the final powder
`weight, w. Calculate the pycnometric density, p, of the sample ac-
`weight, w. Calculate the pycnometric density, p, of the sample ac(cid:173)
`cording to Equation 2.
`cording to Equation 2.
`
`(701) DISINTEGRATION
`(701) DISINTEGRATION
`This test is provided to determine compliance with the limits on
`This test is provided to determine compliance with the limits on
`Disintegration stated in the individual monographs except where
`Disintegration stated in the individual monographs except where
`the label states that the tablets or capsules are intended for use as
`the label states that the tablets or capsules are intended for use as
`troches, or are to be chewed, or are designed as modified-release
`troches, or are to be chewed, or are designed as modified-release
`dosage forms (see Drug Release (724) ). Determine the type of units
`dosage forms (see Drug Release (724)). Determine the type of units
`under test from the labeling and from observation, and apply the
`under test from the labeling and from observation, and apply the
`appropriate procedure to 6 or more dosage units.
`appropriate procedure to 6 or more dosage units.
`For the purposes of this test, disintegration does not imply com(cid:173)
`For the purposes of this test, disintegration does not imply com-
`plete solution of the unit or even of its active constituent. Complete
`plete solution of the unit or even of its active constituent. Complete
`disintegration is defined as that state in which any residue of the
`disintegration is defined as that state in which any residue of the
`unit, except fragments of insoluble coating or capsule shell, re(cid:173)
`unit, except fragments of insoluble coating or capsule shell, re-
`maining on the screen of the test apparatus is a soft mass having
`maining on the screen of the test apparatus is a soft mass having
`no palpably firm core.
`no palpably firm core.
`
`APPARATUS
`APPARATUS
`The apparatus9 consists of a basket-rack assembly, a 1000-mL,
`The apparatus9 consists of a basket-rack assembly, a 1000-mL,
`low-form beaker, 142 to 148 mm in height and having an outside
`low-form beaker, 142 to 148 mm in height and having an outside
`diameter of 103 to 108 mm for the immersion fluid, a thermostatic
`diameter of 103 to 108 mm for the immersion fluid, a thermostatic
`arrangement for heating the fluid between 35° and 39°, and a device
`arrangement for heating the fluid between 35° and 39°, and a device
`for raising and lowering the basket in the immersion fluid at a
`for raising and lowering the basket in the immersion fluid at a
`constant frequency rate between 29 and 32 cycles per minute
`constant frequency rate between 29 and 32 cycles per minute
`through a distance of not less than 5.3 cm and not more than 5.7
`through a distance of not less than 5.3 cm and not more than 5.7
`cm. The volume of the fluid in the vessel is such that at the highest
`cm. The volume of the fluid in the vessel is such that at the highest
`point of the upward stroke the wire mesh remains at least 2.5 cm
`point of the upward stroke the wire mesh remains at least 2.5 cm
`below the surface of the fluid and descends to not less than 2.5 cm
`below the surface of the fluid and descends to not less than 2.5 cm
`from the bottom of the vessel on the downward stroke. The time
`from the bottom of the vessel on the downward stroke. The time
`required for the upward stroke is equal to the time required for the
`, required for the upward stroke is equal to the time required for the
`downward stroke, and the change in stroke direction is a smooth
`downward stroke, and the change in stroke direction is a smooth
`transition, rather than an abrupt reversal of motion. The basket-rack
`transition, rather than an abrupt reversal of motion. The basket-rack
`assembly moves vertically along its axis. There is no appreciable
`assembly moves vertically along its axis. There is no appreciable
`horizontal motion or movement of the axis from the vertical.
`horizontal motion or movement of the axis from the vertical.
`Basket-rack Assembly-The basket-rack assembly consists of
`Basket-rack Assembly—The basket-rack assembly consists of
`six open-ended transparent tubes, each 7.75 ± 0.25 cm long and
`six open-ended transparent tubes, each 7.75 ± 0.25 cm long and
`having an inside diameter of 20.7 to 23 mm and a wall 1.0 to 2.8
`having an inside diameter of 20.7 to 23 mm and a wall 1.0 to 2.8
`mm thick; the tubes are held in a vertical position by two plastic
`mm thick; the tubes are held in a vertical position by two plastic
`plates, each 8.8 to 9.2 cm in diameter and 5 to 7 mm in thickness,
`plates, each 8.8 to 9.2 cm in diameter and 5 to 7 mm in thickness,
`with six holes, each 22 to 26 mm in diameter, equidistant from the
`with six holes, each 22 to 26 mm in diameter, equidistant from the
`center of the plate and equally spaced from one another. Attached
`center of the plate and equally spaced from one another. Attached
`to the under surface of the lower plate is a woven stainless steel
`to the under surface of the lower plate is a woven stainless steel
`wire cloth, which has a plain square weave with 1.8- to 2.2-mm
`wire cloth, which has a plain square weave with 1.8- to 2.2-mm
`mesh apertures and with a wire diameter of 0.60 to 0.655 mm. The
`mesh apertures and with a wire diameter of 0.60 to 0.655 mm. The
`parts of the apparatus are assembled and rigidly held by means of
`parts of the apparatus are assembled and rigidly held by means of
`three bolts passing through the two plastic plates. A suitable means
`three bolts passing through the two plastic plates. A suitable means
`is provided to suspend the basket-rack assembly from the raising
`is provided to suspend the basket-rack assembly from the raising
`and lowering device using a point on its axis.
`and lowering device using a point on its axis.
`The design of the basket-rack assembly may be varied somewhat
`The design of the basket-rack assembly may be varied somewhat
`provided the specifications for the glass tubes and the screen mesh
`provided the specifications for the glass tubes and the screen mesh
`size are maintained.
`size are maintained.
`Disks-The use of disks is permitted only where specified in
`Disks9—The use of disks is permitted only where specified in
`the monograph. If specified in the individual monograph, each tube
`the monograph. If specified in the individual monograph, each tube
`is provided with a cylindrical disk 9.5 ± 0.15 mm thick and 20.7
`is provided with a cylindrical disk 9.5 ± 0.15 mm thick and 20.7
`± 0.15 mm in diameter. The disk is made of a suitable, transparent
`± 0.15 mm in diameter. The disk is made of a suitable, transparent
`plastic material having a specific gravity of between 1.18 and 1.20.
`plastic material having a specific gravity of between 1.18 and 1.20.
`Five parallel 2-mm holes extend between the ends of the cylinder.
`Five parallel 2-mm holes extend between the ends of the cylinder.
`One of the holes is centered on the cylindrical axis. The other holes
`One of the holes is centered on the cylindrical axis. The other holes
`
`are centered 6 mm from the axis on imaginary lines perpendicular
`are centered 6 mm from the axis on imaginary lines perpendicular
`to the axis and parallel to each other. Four identical trapezoidal(cid:173)
`to the axis and parallel to each other. Four identical trapezoidal-
`shaped planes are cut into the wall of the cylinder, nearly perpen(cid:173)
`shaped planes are cut into the wall of the cylinder, nearly perpen-
`dicular to the ends of the cylinder. The trapezoidal shape is sym(cid:173)
`dicular to the ends of the cylinder. The trapezoidal shape is sym-
`metrical; its parallel sides coincide with the ends of the cylinder
`metrical; its parallel sides coincide with the ends of the cylinder
`and are parallel to an imaginary line connecting the centers of two
`and are parallel to an imaginary line connecting the centers of two
`adjacent holes 6 mm from the cylindrical axis. The parallel side of
`adjacent holes 6 mm from the cylindrical axis. The parallel side of
`the trapezoid on the bottom of the cylinder has a length of 1.6 mm,
`the trapezoid on the bottom of the cylinder has a length of 1.6 mm,
`and its center lies at a depth of 1.8 mm from the cylinder's circum(cid:173)
`and its center lies at a depth of 1.8 mm from the cylinder's circum-
`ference. The parallel side of the trapezoid on the top of the cylinder
`ference. The parallel side of the trapezoid on the top of the cylinder
`has a length of 9.2 mm, and its center lies at a depth of 2.6 mm
`has a length of 9.2 mm, and its center lies at a depth of 2.6 mm
`from the cylinder's circumference. All surfaces of the disk are
`from the cylinder's circumference. All surfaces of the disk are
`smooth. If the use of disks is specified in the individual monograph,
`smooth. If the use of disks is specified in the individual monograph,
`add a disk to each tube, and operate the apparatus as directed under
`add a disk to each tube, and operate the apparatus as directed under
`Procedure.
`Procedure.
`
`PROCEDURE
`PROCEDURE
`Uncoated Tablets-Place 1 tablet in each of the six tubes of the
`Uncoated Tablets—Place 1 tablet in each of the six tubes of the
`basket and operate the apparatus, using water maintained at 37 ±
`basket and operate the apparatus, using water maintained at 37 ±
`2° as the immersion fluid unless otherwise specified in the individ(cid:173)
`2° as the immersion fluid unless otherwise specified in the individ-
`ual monograph. At the end of the time limit specified in the mono(cid:173)
`ual monograph. At the end of the time limit specified in the mono-
`graph, lift the basket from the fluid, and observe the tablets: all of
`graph, lift the basket from the fluid, and observe the tablets: all of
`the tablets have disintegrated completely. If I or 2 tablets fail to
`the tablets have disintegrated completely. If 1 or 2 tablets fail to
`disintegrate completely, repeat the test on 12 additional tablets: not
`disintegrate completely, repeat the test on 12 additional tablets: not
`less than 16 of the total of 18 tablets tested disintegrate completely.
`less than 16 of the total of 18 tablets tested disintegrate completely.
`Plain Coated Tablets-Apply the test for Uncoated Tablets, op(cid:173)
`Plain Coated Tablets—Apply the test for Uncoated Tablets, op-
`erating the apparatus for the time specified in the individual
`erating the apparatus for the time specified in the individual
`monograph.
`monograph.
`Delayed-release (enteric coated) Tablets-Place I tablet in each
`Delayed-release (enteric coated) Tablets—Place 1 tablet in each
`of the six tubes of the basket and, if the tablet has a soluble external
`of the six tubes of the basket and, if the tablet has a soluble external
`coating, immerse the basket in water at room temperature for 5
`coating, immerse the basket in water at room temperature for 5
`minutes. Then operate the apparatus using simulated gastric fluid
`minutes. Then operate the apparatus using simulated gastric fluid
`TS maintained at 37 ± 2° as the immersion fluid. After 1 hour of
`TS maintained at 37 ± 2° as the immersion fluid. After 1 hour of
`operation in simulated gastric fluid TS, lift the basket from the fluid,
`operation in simulated gastric fluid TS, lift the basket from the fluid,
`and observe the tablets: the tablets show no evidence of disintegra(cid:173)
`and observe the tablets: the tablets show no evidence of disintegra-
`tion, cracking, or softening. Operate the apparatus, using simulated
`tion, cracking, or softening. Operate the apparatus, using simulated
`intestinal fluid TS maintained at 37 ± 2° as the immersion fluid,
`intestinal fluid TS maintained at 37 ± 2° as the immersion fluid,
`for the time specified in the monograph. Lift the basket from the
`for the time specified in the monograph. Lift the basket from the
`fluid, and observe the tablets: all of the tablets disintegrate com(cid:173)
`fluid, and observe the tablets: all of the tablets disintegrate com-
`pletely. If 1 or 2 tablets fail to disintegrate completely, repeat the
`pletely. If 1 or 2 tablets fail to disintegrate completely, repeat the
`test on 12 additional tablets: not less than 16 of the total of 18
`test on 12 additional tablets: not less than 16 of the total of 18
`tablets tested disintegrate completely.
`tablets tested disintegrate completely.
`Buccal Tablets-Apply the test for Uncoated Tablets. After 4
`Buccal Tablets—Apply the test for Uncoated Tablets. After 4
`hours, lift the basket from the fluid, and observe the tablets: all of
`hours, lift the basket from the fluid, and observe the tablets: all of
`the tablets have disintegrated. If 1 or 2 tablets fail to disintegrate
`the tablets have disintegrated. If 1 or 2 tablets fail to disintegrate
`completely, repeat the test on 12 additional tablets: not less than 16
`completely, repeat the test on 12 additional tablets: not less than 16
`of the total of I 8 tablets tested disintegrate completely.
`of the total of 18 tablets tested disintegrate completely.
`Sublingual Tablets-Apply the test for Uncoated Tablets. Ob(cid:173)
`Sublingual Tablets—Apply the test for Uncoated Tablets. Ob-
`serve the tablets within the time limit specified in the individual
`serve the tablets within the time limit specified in the individual
`monograph: all of the tablets have disintegrated. If 1 or 2 tablets
`monograph: all of the tablets have disintegrated. If 1 or 2 tablets
`fail to disintegrate completely, repeat the test on 12 additional tab(cid:173)
`fail to disintegrate completely, repeat the test on 12 additional tab-
`lets: not less than 16 of the total of 18 tablets tested disintegrate
`lets: not less than 16 of the total of 18 tablets tested disintegrate
`completely.
`completely.
`Hard Gelatin Capsules-Apply the test for Uncoated Tablets.
`Hard Gelatin Capsules—Apply the test for Uncoated Tablets.
`Attach a removable wire cloth, which has a plain square weave with
`Attach a removable wire cloth, which has a plain square weave with
`1.8- to 2.2-mm mesh apertures and with a wire diameter of 0.60 to
`1.8- to 2.2-mm mesh apertures and with a wire diameter of 0.60 to
`0.655 mm, as described under Basket-rack Assembly, to the surface
`0.655 mm, as described under Basket-rack Assembly, to the surface
`of the upper plate of the basket-rack assembly. Observe the capsules
`of the upper plate of the basket-rack assembly. Observe the capsules
`within the time limit specified in the individual monograph: all of
`within the time limit specified in the individual monograph: all of
`the capsules have disintegrated except for fragments from the cap(cid:173)
`the capsules have disintegrated except for fragments from the cap-
`sule shell. If I or 2 capsules fail to disintegrate completely, repeat
`sule shell. If 1 or 2 capsules fail to disintegrate completely, repeat
`the test on 12 additional capsules: not less than 16 of the total of
`the test on 12 additional capsules: not less than 16 of the total of
`18 capsules tested disintegrate completely.
`18 capsules tested disintegrate completely.
`Soft Gelatin Capsules-Proceed as directed under Hard Gelatin
`Soft Gelatin Capsules—Proceed as directed under Hard Gelatin
`Capsules.
`Capsules.
`
`(711) DISSOLUTION
`(711) DISSOLUTION
`This test is provided to determine compliance with the dissolu(cid:173)
`This test is provided to determine compliance with the dissolu-
`tion requirements where stated in the individual monograph for a
`tion requirements where stated in the individual monograph for a
`tablet or capsule dosage form. Of the types of apparatus described
`tablet or capsule dosage form. Of the types of apparatus described
`herein, use the one specified in the individual monograph. Where
`herein, use the one specified in the individual monograph. Where
`the label states that an article is enteric-coated, and a dissolution or
`the label states that an article is enteric-coated, and a dissolution or
`
`

`

`1942
`1942
`
`(711) Dissolution / Physical Tests
`711) Dissolution / Physical Tests
`
`USP 24
`USP 24
`
`disintegration test that does not specifically state that it is to be
`disintegration test that does not specifically state that it is to be
`applied to enteric-coated articles is included in the individual mono-
`applied to enteric-coated articles is included in the individual mono(cid:173)
`graph, the test for Delayed-release Articles under Drug Release
`graph, the test for Delayed-release Articles under Drug Release
`(724) is applied unless otherwise specified in the individual mono-
`(724) is applied unless otherwise specified in the individual mono(cid:173)
`graph. For hard gelatin capsules that do not conform to the Dis-
`graph. For hard gelatin capsules that do l}Ot conform to the Dis(cid:173)
`solution specification, repeat the test as follows. Where water is not
`solution specification, repeat the test as follows. Where water is not
`specified as the Medium in the individual monograph, the same
`specified as the Medium in the individual monograph, the same
`Medium specified in the monograph may be used with the addition
`Medium specified in the monograph may be used with the addition
`of not more than 3.2 g of purified pepsin having an activity of 800
`of not more than 3.2 g of purified pepsin having an activity of 800
`to 2500 units per mg of protein, or not more than 5 g of pancreatin,
`to 2500 units per mg of protein, or not more than 5 g of pancreatin,
`per 1000 mL of Medium, as appropriate. Pepsin is added to acidic
`per 1000 mL of Medium, as appropriate. Pepsin is added to acidic
`media, while pancreatin is appropriate for media at or above a pH
`media, while pancreatin is appropriate for media at or above a pH
`of 6.8. Where the monograph specifies water as the Medium, a
`of 6.8. Where the monograph specifies water as the Medium, a
`second medium of either 0.1 N hydrochloric acid with pepsin or
`second medium of either 0.1 N hydrochloric acid with pepsin or
`pH 6.8 phosphate buffer with pancreatin, depending on the drug
`pH 6.8 phosphate buffer with pancreatin, depending on the drug
`solubility, may be used with the concentration of pepsin or pancre-
`solubility, may be used with the concentration of pepsin or pancre(cid:173)
`atin being the same as above.
`atin being the same as above.
`USP Reference Standards (I 1)-USP Prednisone Tablets RS
`USP Reference Standards ( I 1)-USP Prednisone Tablets RS
`(Dissolution Calibrator, Disintegrating). USP Salicylic Acid Tab(cid:173)
`(Dissolution Calibrator, Disintegrating). USP Salicylic Acid Tab-
`lets RS (Dissolution Calibrator, Nondisintegrating).
`lets RS (Dissolution Calibrator, Nondisintegrating).
`Apparatus I-The assembly consists of the following: a covered
`Apparatus 1-The assembly consists of the following: a covered
`vessel made of glass or other inert, transparent material'; a motor;
`vessel made of glass or other inert, transparent material'; a motor;
`a metallic drive shaft; and a cylindrical basket. The vessel is par-
`a metallic drive shaft; and a cylindrical basket. The vessel is par(cid:173)
`tially immersed in a suitable water bath of any convenient size or
`tially immersed in a suitable water bath of any convenient size or
`placed in a heating jacket. The water bath or heating jacket permits
`placed in a heating jacket. The water bath or heating jacket permits
`holding the temperature inside the vessel at 37 ± 0.5° during the
`holding the temperature inside the vessel at 37 ± 0.5° during the
`test and keeping the bath fluid in constant, smooth motion. No part
`test and keeping the bath fluid in constant, smooth motion. No part
`of the assembly, including the environment in which the assembly
`of the assembly, including the environment in which the assembly
`is placed, contributes significant motion, agitation, or vibration be-
`is placed, contributes significant motion, agitation, or vibration be(cid:173)
`yond that due to the smoothly rotating stirring element. Apparatus
`yond that due to the smoothly rotating stirring element. Apparatus
`that permits observation of the specimen and stirring element during
`that permits observation of the specimen and stirring element during
`the test is preferable. The vessel is cylindrical, with a hemispherical
`the test is preferable. The vessel is cylindrical, with a hemispherical
`bottom and with one of the following dimensions and capacities:
`bottom and with one of the following dimensions and capacities:
`for a nominal capacity of I liter, the height is 160 mm to 210 mm
`for a nominal capacity of 1 liter, the height is 160 mm to 210 mm
`and its inside diameter is 98 mm to 106 mm; for a nominal capacity
`and its inside diameter is 98 mm to 106 mm; for a nominal capacity
`of 2 liters, the height is 280 mm to 300 mm and its inside diameter
`of 2 liters, the height is 280 mm to 300 mm and its inside diameter
`is 98 mm to 106 mm; and for a nominal capacity of 4 liters, the
`is 98 mm to 106 mm; and for a nominal capacity of 4 liters, the
`height is 280 mm to 300 mm and its inside diameter is 145 mm to
`height is 280 mm to 300 mm and its inside diameter is 145 mm to
`155 mm. Its sides are flanged at the top. A fitted cover may be used
`155 mm. Its sides are flanged at the top. A fitted cover may be used
`to retard evaporation.2 The shaft is positioned so that its axis is not
`to retard evaporation.2 The shaft is positioned so that its axis is not
`more than 2 mm at any point from the vertical axis of the