Oral Solid Dosage Forms Guide

_________________________________________________________ _ Introduction
Oral solid Dosage forms

Introduction
Dosage forms:
It is a transformation of a pure chemical compound in to a predetermined form by
admixing drug component with different kinds of non-drug component knows as
additives.
Tablets:
Tablets are the most extensively used solid dosage form. They are prepared by molding
or usually compression.
Advantages of Tablets:
1. They are a unit form and they offer the greatest capabilities of all oral dosage
forms for the greatest dose precision and the least content variability.
2. Their cost is lowest of all oral dosage forms.
. They are the lightest and most compact of all oral dosage forms.
!. They are in general the easiest and the cheapest to package and ship of all oral
dosage forms.
". #roduct identification is potentially the simplest and cheapest$ re%uiring no
additional processing steps when employing and embossed or monogrammed
punch face.
&. They may provide the greatest ease of swallowing with the least tendency for
'hung-up( above the stomach$ especially when coated$ provider that tablet
disintegration is not excessively rapid.
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_________________________________________________________ _ Introduction
-. They lend themselves to certain special release profile product such as enteric or
delayed .release products.
+. They are better suited to large-scale production then other unit oral forms.
/. They have the best .combined properties of chemical$ mechanical and
microbiologic stability of all the oral forms.
Disadvantages of Tablets:
1. 0ome drugs resist compression in to dense compacts$ owing to their amorphous
nature or flocculent$ low density character.
2. 1rugs with poor wetting$ slow dissolution properties$ intermediate to large
dosage. 2ptimum absorption high in gastrointestinal tract or any combination of
these features may be difficult or impossible to formulate and manufacture as a
tablet that will still provide ade%uate or full drugs bioavailability.
. 3itter-testing drugs$ drugs with an ob4ective odor$ or drugs that are sensitive to
oxygen or atmospheric moisture may re%uire encapsulation or entrapment prior
to compression$ or the tablet may re%uire coating .In such cases$ the capsules
may offer the best and lowest cost approach.
CAPSULES:
There are two main types of capsules and both are available in a variety of si5es. 6ike
cachets they are useful for unpleasant medicaments.
1. ard capsules are for solid medicaments. They consist of a cylindrical body
and cap. 3oth with hemispherical end$ and are usually made from gelatin and
water with added preservative. 7lthough %uite hard$ they soften readily and
dissolve after swallowing with water.
2. Soft capsules are for solids li%uids and semi-solids. They may be spherical$
ovoid or cylindrical with hemispherical ends. In addition to the ingredients of
hard capsules$ they contain glycerol$ which provides the flexibility.
_________________________________________________________ _ Introduction
Advantages of Ca!sules:
1. They obscure the taste and odor of unpleasant drugs.
2. They are attractive in appearance.
. They are slippery when moist$ and hence easy to swallow with a draught of
water.
!. If properly stored the shells contain 12-1" percent of moisture which gives
flexibility and$ conse%uently$ very considerable resistance to mechanical
stresses.
". 6ess ad4uncts are necessary than for tablets.
&. The contents are usually in fine powder$ which combined with freedom or
near freedom from ad4uncts$ provides rapid and uniform release of
medicaments in the gastro-intestinal tract.
-. The shells can be pacified or colored$ to gibe protection from light.
+. The shells are made to very fine limits8 hence the cap and base fit well and
give substantial protection against air moisture.
/. The shells are physiologically inert and easily and %uickly digested in the
gastrointestinal tract.
1,. #resentation of a drug in capsules$ rather then in tablets$ allows %uicker
submission of a new drug for clinical trials$ because fewer development
problems are involved .also it is easier to vary the dose.
11. 9omplicated machinery is unnecessary for the extemporaneous dispensing
of a few capsules.
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Monograph
CLASSI"ICATIO# O" SOLID DOSA$E "O%&
'( As suc)
*a( Oral
*i+( Divided !o,der
0imple powder
9ompound powder
*ii+( -ul. !o,der
:ffervescent powder
7ntacid
6axatives
1ietary

*-( E/ternal
1usting powder
0nuff
Insufflations
0prays
7erosols
1entifrices
*C ( Parenterals
0( Com!ressed
Tablets
9apsules
9achets
1( &oulded
0uppositories
Tablet triturates
6o5enges
#astilles
#ills
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_________________________________________________________
Monograph
&O#O$%AP:
TA-LETS
DE"I#ITIO#:
Tablets are solid dosage forms each containing a unit dose of one or more medicaments.
I;T<21=9TI2;:
They are intended for oral administration. 0ome tablets are swallowed whole or after
being chewed$ some are dissolved or dispersion in water before administration and
some are retained in mouth where the active ingredient is liberated. #reparation
intended for administration by other routes$ for example$ in the form of implants and
passerines may also be presented in the form of tablets but because they may re%uired
special formulations$ methods of manufacture or from of presentation appropriate to the
particular use they may not comply with all the re%uirement of this monograph.
Tables are obtained by compression of uniform volumes of powders or granules by
applying high pressure and using punches and dies. The particles to be compressed
consist of one or more medicaments$ with or without auxiliary substance such as
diluents$ binders$ and disintegration agents$ lubricant$ glide ants and substances capable
of modifying the behavior of the medicaments inn the digestive tracts. 0uch substances
must be innocuous and therapeutically inert in the %uantities present.
3ecause of their composition$ method of manufacture or intended use$ tablets present
variety of characteristics and conse%uently there are several categories of tablets.
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_________________________________________________________
Monograph
=seless otherwise stated in the individual monograph$ tablets are uncoated. >here
coating is permitted the monograph directs coating the statement reads 'The tablets are
coated '
=nless otherwise directed$ tablets may be coated in one of different ways.
$E#E%AL CA%ACTE%STICS:
Tablets are usually solid$ right circulars cylinders$ the end surfaces of which are flat or
convex and the edges of which may be beveled$ they may exist in others shapes like
triangular$ rectangular$ etc also. They may have lines or break-marks and may bear a
symbol or other markings. They are sufficiently hard to withstand handling without
crumbling or breaking.
I#DIA# PA%&ACIA %E2UI%E&E#TS:
U#COATED TA-LETS:
=ncoated tablets may be signal-layer tablets resulting from a signal compression of
particles or multi-layer tablets costing of parallel layers obtained by successive
compression of particles of different compositions .$ no treatment is applied to such
tablets after compression 7ny added substances are not ingredients in the digestive
fluids
The addition of coloring or flavorings agents to uncoated tablets other than multi-layer
tablets is not official unless permitted in the individual monograph. =ncoated tablets
have the general characteristics of tablets. >hen a bracken section of uncoated tablet if
the tablets fail to comply the discs the tablets comply the if all six have disintegrated.
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I#DIA# PA%&ACOPEIAL %E2UIE&S
COATED TA-LETS:

9oated tablets are covers with one or more layers mixture of various substances such as
resins$ gums$ inactive$ and insoluble fillers$ sugars$ plastici5es polyhydric alcohols$
waxes$ etc. the coating may also contain medicaments in compression-coated tablets
the coated is applied by compressing around the tablets granules prepared from tablets
the coating is applied as a coating are usually applied as a solution or suspension in
condition in which evaporation of the vehicle occurs. >hen the coating is thin$ the
tablets are described as a film coated. 9oated tablets may contain flavoring and or one
or more coloring agents permitted under the drug and cosmetic rules 1/!"
9oated tablets have a smooth. =sually polished and after colored. 0urface: a broken
sections examined under a lens shows a core surrounded by one or one more
continuous layers of a different texture.
-%ITIS PA%&ACOPEIAL %E2UI%E&E#TS:

DISI#TE$%ATIO# TESTS:
9oated tablets other than film-coated tablets comply the test for disintegration of tablets
and capsules use water < a li%uids medium add a disc to each tube operate the
apparatus for &, minuets unless otherwise 4ustified and authori5ed and examine the
state of the tablets if any has not disintegrated repeats the test on a further six tablets
replacing water < which ,.1 ? hydrochloric acid the tablets comply with the test if all
six tablets have disintegrated in the acid medium.
@ilm.coated tablets comply with the disintegration test pre cribbed over expect that the
apparatus is operated for , minute unless otherwise 4ustified and authori5ed.
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If coated tablets or film-coated tablets fail to comply because of adherence to the discs
repeat the test on a further six tablets omitting the discs the tablets comply with the test
if all six have disintegrated.
I#DIA# PA%&ACOPEIAL %E2UI%E&E#TS:
E#TE%IC3COATED TA-LETS
:nteric .coated tablets Agastric .resistant tabletsB are tablets with one or more layers of
coatings intended to resist the gastric fluid but to release their active ingredients in the
intestinal fluid. @or this purpose substance such as acetate phthalate and anionic
copolymer of met acrylic acid and its ethers are used for providing tablets with a
gastricC-resistant coating to for covering either granules or particles with gastric .
resistant coating :nteric.coated tablets have the characteristics of coated tablets.
P%ODUCTIO#:
@or tablets prepared form granules or particles already covered with a gastro-resistant
coating a 0uitable test is carried out to demonstrate of the active substances
@or tablets wit a gastro-resistance coating carry out the test for disintegration with the
following modifications use ,.1 ? hydrochloric acid. 7s the li%uid medium operate the
apparatus for 2 hr or other such time as may be 4oisted and authori5ed without the discs
and ermine the tablets the time of resistance to the acid medium various according to
the formulation of the tablets to be examined it is typically 2 hr to hr but even with
authori5ed deviations is not less than 1 hr ;o tablets show signs of either
disintegrations Aapart from the fragment of coating B or creaks that would that allow the
escape of the contents <eplace the acid by phosphate buffer solution pD &.+ < and a
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disc to each tube. 2perate the apparatus for the &, minutes and examine and the state
of each tablets if the tablets fail to comply of adherence to the discs$ repeat the test on a
further six tablets omitting the discs the tablets comply with the test if all have
disintegrated .
1ispersible tablets are uncoated tablets that procedure a uniform dispersion in water
and ?ay contains permitted colorings and flavorings agents.
"I#E#ESS O" DISPE%SIO#:
#lace two tablets in 1,, ml of water < and stir completely dispersed a smooth
dispersion is produce which oases though a serve screen with a nominal mesh aperture
is procure of -1, micro meters.
&ODI"IED 4 %ELEASE TA-LETS:
?odified . release tablets A0ustained. releases tabletsB are coated ort uncoated
containing auxiliary substances or prepared by procedures that separately or together$
are designed to modify the rate or the place at which the ingredients is released.
P%ODUCTIO#:
7 suitable test is carried out to demonstrate the appropriate release of the active
ingredients.
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SOLU-LE TA-LETS:
0oluble tablets are uncoated that dissolve in water. The solution may be slightly
opalescent due to added substances used in the manufacture of the tablets.
DISITE$%EATIUO# TEASTS:
0oluble tablets disintegrate within minutes when examined by the test for
disintegration of tablets and capsules$ but water < at 1" to 2" degree 9.
E""E%5E#CE#T TA-LETS:
:ffervescent tablets are uncoated tablets generally containing acidic substances and
either carbonates or bicarbonates $ which react rapidly in the presence of water to
release carbon dioxide they are intended to be dissolved or dispersed in water before
administration$
DISITE$%EATIUO# TEASTS:
#lace tablets in a breaker containing 2,, ml of water < at 1" degree to 2" degree:
numerous bubbles of gas are evolved when the evolution of gas around the tablets or its
fragments creases the tablets has disintegrated$ being either dissolved or dispersed in
the water sp that no agglomerates of particles remain. <epeat the oration on five other
tablets the comply with the if each of the six tablets used disintegrates in the manner
prescribed within " minutes$ unless otherwise 4ustified and authori5ed.
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TA-LETS "O% USE I# TE &OUT:
Tablets for use in the mouth are usually uncoated tablets to be chewed or to affect a
slow release and local action of the active ingredients Alo5engesB or the release and
absorption of the active ingredients under the tongue Asublingual tabletsB.
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STA#DA%DS:
Uniformit6 of container contents:
Tablets comply with the test for contents of packaged dosage forms$ 7ppendix 11.2
CO#TAE#TS O" PAC7$ED DOSA$E "%O&S:
The following tests and specification apply to oral dosage forms and preparations
intended for topical use that use that are packaged in containers in which the labeled net
%uantity is not more than 1,,g or ,,ml or 1,,, units$ as the case many be. @or higher
labeled %uantities the test and limit given in the stammered of weighing and measure
A#ackaged commoditiesB.
CO#TE#T O" TE ACTI5E I#$%EDIE#T:
1etermine the 7mount of active ingredients by the method described in the assay and
calculate the amount of active ingredients started in the monograph this range is based
on the re%uirements that 2, tablets or such other numbers as may be indicated in there
monograph are used in the assay where 2, tablets cannot be obtained $ a small number
which must not be less than " may be used but to allow for sampling errors the
tolerances are winded in accordance with table 1 the re%uirements of table 1 apply
when the stated limits are between /1 and 11,E for the limits than /, to 11,E
proportionately smaller or larger allowances should be made
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Table3'
8EI$ O" ACTI5E
I#$%EDIE#TS I#
EAC TA-LETS
SU-T%ACT "%O& LO8E%
LI&IT O" SA&PLES
ADD TO TE UPPE% LI&IT
"O% SA&PLES O"
1" 1, " 1" 1, "
,.12g or less ,.2 ,.- 1.& ,. ,.+ 1.+
?ore than ,.12 g but
less ,. g
,.2 ,." 1.2 ,. ,.& 1."
,. or more ,.1 ,.2 ,.+ ,.2 ,.! 1.,
U#I"O%&IT9 O" 8EI$T:
This is not applicable to coated tablets other than film-coated to tablets that are re%uired
to comply with the test for uniformity of content for all active ingredients.
>eight 2, tablets selected at random and cal cute the average weight not more than two
individual weight deviate by more than the percentage shown in table-2 and none
deviates by more than twice that percentage.
Table30
A5E%A$E 8EI$T O" TA-LET PE%CE#TA$E DE5IATIO#
+, mg more less 1,
?ore than +,mg but less than 2",mg -."
2", mg or more "
U#I"O%&IT9 O" CO#TE#T:
This test is applicable to tablets that contain less 1,mg or less than 1,E w)w of active
ingredient for tablets containing more than active ingredient carry out the test for each
active ingredient that corresponds to the aforementioned conditions.
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This trust for uniformity of content should be cared out after only the content the active
ingredients in a pooled sample of the started content. The test for uniformity of
contently is not applicable to tablets containing multivitamins and trace elements.
1etermine the content of the active ingredient in each of 1, tablet at random using
method given in the monograph or by any other suitable analytical method the tablets
comply with there test if not more of the individual values are outside the limits -" to
12"E repeat the determination using another 2, tablet the tablet comply with the test if
in individual values are outside the limit +" to 11"E and outside the limits -" to 12" E
of the average value.
DISI#TE$%ATIO#:
This test is not applicable to modified .release tablets and for use in the mouth for
those tablets for which the dissolution test for tablets and capsules 7ppendix -. is
included in the individual monograph$ the disintegration is not re%uired.
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DISSOLUTIO# TEST "O% TA-LETS A#D CAPSULES:
=se apparatus 1 unless otherwise directed. 7ll parts of the apparatus that many into
contact with preparation being examined or with the dissolution medium are chemically
insert and do not absorb$ react or interfere with the preparation being examined all
metal parts of the apparatus that may come into the contact with the preparation or the
dissolution medium mist be made from stainless steel$ type 1& or e%uivalents or coated
with a suitable material to ensure that such parts do not react or interfere with the
preparation being examined or the dissolutions medium.
APPA%ATUS3':
An assembl6 consisting of t)e follo,ing:
a. 7 cylinder vessel$ 7$ made of borosilicate glass or any other
suitable transparent material$ with a hemispherical bottom and with a nominal
capacity of 1,,,ml. the vessel has a flanged upper rim and is fitted with a lid
number of openings$ one of which is central.
b. 7 motor with a speed regular capable of maintaining the speed of
rotation of the paddle within !E of that specific in the individual monograph. The
motor is fitted with a stirring element. >hich consists of a drive shaft and blade
forming a paddle$ 3 the blade passes thought the diameter of the shaft so that the
bottom of the blade is flush with the bottom of the shaft the shaft is positioned so
that its is axis is within 2 mm of the axis of the vessel and the lower edge of the
blade is 2 to 2- mm from the inside bottom of the vessel. The apparatus operates
in such a way that the paddle rotates smoothly and without significant wobble.
c. 7 water-bath set to maintain the dissolution at &." to -."
degree. The bath li%uid is kept in constant and smooth motion during the set the
vessel is securely clamped in the water bath in such a way that the displacement
vibration from other e%uipment. Including the water circulation device$ is
minimi5ed.
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APPA%ATUS30:
The assembly is the same as in apparatus 1 expect that in the string element the paddle
is replaced by a basket$ 1 Asee -.- and -.-!B the metallic shaft rotates smoothly and
without significant wobble the top part with a vent is attached to the shaft 9. it is fitted
with three spring clips$ or other suitable means that allow removal of the lower part for
the introduction of the preparation being examined and that firmly holds the basket
concentric with the axis of the vessel during rotation the lower detachable part of the
basket is made of welded-seam cloth$ with a write thickness of ,.2"! mm diameter and
wit ,.+1 mm s%uire openings$ formed into a cylinder with a narrow rim of sheet metal
around the top and the bottom. The basket may be plated with a 2." micro meter layer
of gold for use with acidic media. The distance between the inside bottom the of the
vessel and basket is maintained at 2 to 2- mm during the test.
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DISSOLUTIO# &%DIU&:
=se the dissolution medium specified in the individual monograph. If$ the medium is a
buffered solution$ so that$ its pD is within ,.," units of the specified in the monograph.
The dissolution medium should be departed prior to testing.
TI&E:
>here a single time specification is given in the monograph$ the test may be concluded
in a shorter period if the re%uirement for the minimum amount dissolved is met. If two
or more times are specified$ specimens are to be withdrawn only at the stated times$
within a tolerance of F2E.
&ETOD:
Introduce the stated volume of the dissolution medium$ free from dissolved air$ into the
vessel of the apparatus. >arm the dissolution medium to between &." and -." degree.
=nless otherwise stated use one tablet or capsules.
>hen apparatus 1 is used$ allow the tablet or capsule to sink to the bottom of the vessel
prior to rotation of the paddle. 7 suitable device such as a wire or glass helix may be
used to keep hori5ontal at the bottom of the vessel or capsules that would otherwise
float. 9are should be taken to ensure that air bubbles excluded from the surface of the
tablet or capsule. >hen the apparatus 2 is used$ place the tablet or capsule in a dry
basket at the beginning of each test. 6ower the basket into a position before rotation.
2perate the apparatus immediately at the speed of rotation specified in the individual
monograph.
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7pparatus is used$ place glass beads of a suitable si5e$ preferably ,./ to 1.1 mm in
diameter$ with one bead of !." to "." mm in diameter at the bottom of the cone to
protect the fluid entry of the tube an d introduce the tablet or capsule in the cell on or
within the layer of glass beads or by means of a holder. 7ssemble the filter based and
fix the parts together by means of a suitable clamping device. >arm the dissolution
medium to between &." to -." degree and introduce it through the bottom of the cell
using a suitable pump to obtain a suitable pump to obtain a suitable continuous flow at
the specified rate AF"EB.
I#DIA# PA%&ACOPEIAL %E2UI%&E#TS:
>ithin the time interval specified$ or at each time stated$ withdraw a specimen from a
5one midway between the surface of the dissolution medium and the top the rotating
blade or basket$ not less than 1, mm from the wall of the vessel. :xcept in the case of
single sampling$ add a volume of dissolution medium e%ual to the volume of the
sample withdrawn. #erform the analysis as directed in the individual monograph8
<epeat the whole operation five times. >here two or more tablets or capsules are
directed to be placed together in the apparatus$ carry out six replicate tests.
@or each of the tablet or capsule tested$ calculate the amount of dissolved active
ingredients in the solution as a percentage of the stated amount. >here two or more
tablets or capsules are placed together$ determine for each test the amount of active
ingredient in the solution. #er tablet or capsules and calculate as a percentage of the
stated amount. If the result do not confirm to the re%uirements at stage 01 given in the
accompanying acceptance table Atable 1B$ continue testing with additional tablets or
capsules through stage 02 and 0 unless the result conform at stage 02.
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>here the capsule shells interfere with the analysis$ remove the contents of not less
than & capsules as completely as possible$ and dissolve the empty capsule shells in the
specified volume of the dissolution medium. #erform the analysis as directed in the
individual monograph. ?ake any necessary correction. 9orrection factor should not be
greater than 2"E of the stated amount.
TA-LE '3Acce!tance Table
STA$E #U&-E%
TESTED
ACCEPTA#CE
C%ITE%IA
01 &
:ach unit is not less than
1GF"E
02 &
7verage of 12 units A01F02B is e%ual
to or greater than 1 and no unit is less
than 1-1"E.
0 12
7verage of 2! units A01F02F0B is
e%ual to or greater than 1$ not more
than 2 units are less than 1-1"E and
no unit is less than 1-2"E.
G1 is the amount of dissolved active ingredient specified in the individual monograph.
:xpressed as a percentage of the stated amount.
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U#COATED TA-LETS:
9omply with the disintegration test for tablets and capsules$ 7ppendix -.1. =nless
otherwise directed in the individual$ use water as the medium and add to each tube.
2perate the apparatus for 1" minutes unless otherwise directed.
DISI#TE$%ATIO# TEST "O% TA-LETS A#D CAPSULES:
This time determines whether tablets or capsules disintegrate within a prescribed time
when placed in a li%uid medium under the prescribed experimental conditions.
@or the purpose of this test$ disintegration dose not imply complete solution or the
tablet of capsule or even its active constituent. 1isintegration is defined as that state in
which no residue of the tablet or capsule remains on the screen of the apparatus or$ if a
residue remains$ it consist of fragments of insoluble coating of the tablet of capsule
shells or is a soft mass with no palpable core. If discs have been used with capsules$
any residue remaining on the lower surfaces of the discs consist only of fragments of
shells.
APP%ATUS:
a. 7 rigid basket-rack assemble supporting six cylindrical glass tubes$ --."F2." mm
long$ 21." mm in internal diameter and with a wall thickness of about 2 mm.
b. The tubes are held vertically by two superimposed transparent plastic plates$ /, mm
in diameter and & mm thick$ perforated by & holes having the same diameter as the
tubes. The holes are e%uidistant from the center of the plate and are e%ually spaced
from one another. 7ttached to he under side of the lower plate is a piece of woven
gau5e made from stainless steel wire &" micro I n diameter and having nominal
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mesh apertures of 2.,, mm. The upper plate is covered with those of the upper
plastic plate and upper open ends of the glass tubes.
c. The plates are held rigidly in position and --." mm apart by vertical metal rods at
the periphery and a metal rod is also fixed to the center of the upper plate to enable
the assembly to be attached to a mechanical device capable of raising and lowering
it smoothly at a constant fre%uency of between 2+ and 2 cycles per minute through
a distance of ", to &, mm. The design of the basket- rack assembly may be some
what different provided specifications for the glass tubes and the screen mesh si5e
are unchanged.
d. 7 cylindrical disc for each tube$ each 2,.- F ,.1" mm in diameter and /." F,.1"
mm thick. ?ade of transparent plastic with a relatively density of 1.1+ to 1.2,$ and
pierced with five holes$ each 2 mm diameter$ in the center and other four spaced
e%ually on a circle of radius & mm form the center of the disc. @our e%ually spaced
grooves are cut in lateral surface of the disc in such a way that at the upper surface
of the disc they are /." mm wide and 2."" mm deep ands at the lower surface 1.&
mm s%uare.
e. The assembly is suspended in the li%uid medium in a suitable vessel$ preferably a
1,,,-ml beaker. The volume of li%uid is such that the wire mesh at its highest point
is at least 2" mm below the surface of the li%uid$ and at its lower point is at least 2"
mm above the bottom of the beaker.
f. 7 thermostatic arrangement for heating the li%uid and maintaining the temperature
at -F2 degree.
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-%ITIS PA%A&ACOPEIAL %E2UI%&E#TS:
APP%ATUS:
a. 7 rigid basket-rack assembly supporting six cylindrical glass tubes -"., to +,., mm
long$ 21." mm in internal diameter and with a wall thickness of about 2 mm.
b. 7 cylindrical disc for each tube$ each 2,."" to 2,.+" mm in diameter and /." to
/.&" mm thick$ made of transparent plastic with a relative density of 1.1+ to1.2,.
#ierced with five holes$ each 2 mm in diameter$ one in the center and the four
spaced e%ually on a circle of radius & mm from the center of the disc. @our e%ually
spaced grooves are cut the lateral surface of the disc in such way that at the upper
surface of the disc they are /." mm wide and at the lower surface 1.& mm s%uare.
c. The tubes are held vertically by two superimposed transparent plastic plates /, mm
in diameter and thick$ perforated by six holes. The holes are e%uidistant from the
center of the plate and are e%ually spaced from the center of the plate is apiece of
woven gau5e made from stainless steel wire ,.&" mm in diameter an having
nominal mesh aperture of 2.,, mm.
d. The plates are held rigidly in position and --." mm apart by vertical metal to enable
the periphery and a metal of is also fixed to the center of the upper plate to enable
the assembly to be attached to a mechanical device capable of raising and lowering
it smoothly through a distance of ", to &, mm at a constant fre%uency of between
2+ and 2 cycles per minute.
e. The assembly is suspended in the specified li%uid medium in a suitable vessel$
preferably a 1,,,-ml beaker. The volume of li%uid is such that when the assembly
is in the highest position the wire mesh is at least 1" mm below the surface of the
li%uid and when the assembly is in the assembly is in lowest the wire mesh is at
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least 2"mm a the bottom of the beaker and upper open ends of the tubes remain
above the surface of the li%uid.
f. 7 suitable device maintains the temperature of the li%uid at & to + degree.
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"igure II
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&ETOD:
=nless otherwise stated in the individual monograph$ one tables or capsule into each
tube and$ if directed in the appropriate general monograph$ add a disc to each tube.
0uspend the assembly in the beaker containing the specified li%uid and operate the
apparatus for the specified time. <emove the assembly from the li%uid. The tablets or
capsules pass the test if all of them have disintegrated
If the tablets or capsules fail to disintegrate$ repeat the test on 12 additional tablets or
capsules8 not less then1& of the total of 1+ tablets or capsules tested disintegrate.
If the tablets or capsules adhere to the disc and the operation being examined fails to
comply$ repeat the test omitting the disc. The preparation complies with the test if all
the tablets or capsules in the repeat test disintegrate.
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-%ITIS PA%A&ACOPEIAL %E2UI%&E#TS:
LA%$E TA-LETS A#D LA%$E CAPSULES:
APPA%ATUS:
1. 7 rigid basket-rack assembly supporting three cylindrical glass tubes -"., to
+,., long$ 2." to ." mm in internal diameter and with a wall thickness of 2.,
to ., mm.
2. 7 cylindrical discs for each tube$ each 1.!, to 1.-, mm in diameter and 1&.
to 1&." mm in thick$ made of transparent plastic with a relative density of 1.1+
to 1&." mm in thick$ made of transparent plastic with a relative density of 1.1+
to 1.2,$ pierced with seven holes$ each .1" mm in diameter$ one in the center
and the other six spaced e%ually on a circle of radius !.2 mm from the center of
the disc.
. The tubes are held vertically by two superimposed transparent plastic plates /-
mm in diameter and / mm thick$ perforated by three holes. The holes are
e%uidistant from the center of the plate and are e%ually spaced from one another.
7ttached to the under side of the lower plate is a piece of woven gau5e made
from stainless steel wire o.&, to ,.&! mm in diameter and having mesh
apertures of 1.1+ to 2.2 mm.
!. The plates are held rigidly in position and --." mm apart by vertical metal road
at the periphery and a metal rod is also fixed to the center of the upper plate to
enable the assembly to be attached to a mechanical device capable of raising of
" to "- mm at a constant fre%uency of between 2/ and 2 cycles per minute.
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". The assembly is suspended in the specified li%uid medium in a suitable vessel$
preferably a 1,,-ml beaker. The volume of li%uid is such that when the
assembly is in position the wire mesh is at least 1" mm below the surface of the
li%uid and when the assembly is in the lowest position the wire mesh is at least
2" mm above the bottom of the li%uid.
&. 7 suitable device maintains the temperature of the li%uid at " to/ degree.
COATED TA-LETS:
9omply with the disintegration test for tablets and capsules$ 7ppendix -.1. =nless
otherwise directed in the individual monograph$ use water as the medium and add a
disc to each tube. 2perate the apparatus for , minutes for film-coated and for &,
minutes for other coated tablets unless otherwise directed in the individual monograph.
@or coated tablets other than film-coated tablets$ if any of the tablets have not
disintegrated$ repeat the test on a further & tablets$ replacing the water in the vessel with
,.1 m hydrochloric acid. The tablets comply with the test if all & tablets have
disintegrated in the acid medium.
E#TE%IC COATED TA-LETS:
9omply with the disintegration test tablets and capsules. 7ppendix-.1. If the tablet has
a soluble coating$ immerse the basket in the water at room temperature for " minutes.
0uspend the assembly in the beaker containing ,.1 m hydrochloric acid and operate
without the disc for 12, minutes$ unless otherwise stated in the individual monograph.
<emove the assembly from the li%uid. ;o tablet shows a sign of cracks that would
allow the escape of the contents of disintegration$ apart from fragments of coating.
<eplace the li%uid in the beaker with mixed phosphate buffer ph &.+$ add a disc to each
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tube and operate the apparatus for a further &, minutes. <emove the assembly from the
li%uid. The tablets pass the test if all six have disintegrated.
-%ITIS PA%&ACOPIEAL %E2UI%&E#TS:
&ETOD:
Introduce one tablet into each tube$ suspend the assembly in the beaker containing
,.1? hydrochloric acid and operate without the discs for 12, minutes$ unless otherwise
stated in the individual monograph. <emove the assembly from the li%uid. ;o tablet
shows signs of cracks that would allow the escape of the contents or disintegration$
apart from fragments of coating.
<eplace the li%uid in the beaker with mixed phosphate buffer pD &.+$ add a disc to each
tube an operate the apparatus for a further &, minutes. <emove the assembly from the
li%uid. The tablets pass the test if all six have disintegrated.
DISPE%SI-LE A#D SOLU-LE TA-LETS:
1isintegrate within minutes when examined by the disintegration test for tablets and
capsules$ 7ppendix -.1$ using water at 2! and 2& degree. =nless otherwise stated in the
individual monograph.
EE"E%5ESCE#T TA-LETS:
#lace one tablet in a 2",-ml beaker containing water at 2, to , degree8 numerous gas
bubbles are evolved. >hen the evolution of gas around the tablet or its fragment has
ceased the tablet shall have disinter grated$ being either dissolved or dispersed in the
water so that no agglomerates of particles remain. <epeat the operation on the further
five tablets. The tablets comply with the test if each of the & tablets disintegrates in the
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manner prescribed within " minutes$ unless otherwise stated in the individual
monograph.
Uniformit6 of Dis!ersion:
This test is applicable only to dispersible tablets. #lace 2 tablets in 1,, ml or water and
stir gently until completely dispersed. 7 smooth dispersion is obtained which passes
through sieve screen with a nominal mesh aperture of -1, micro meters Asieve number
22B.

DISSOLUTIO# TEST "O% TA-LETS A#D CAPSULES AS PE%
-%ITIS PA%&ACOPIEA:
APPA%ATUS 1 *"LO83T%OU$ CELL APPA%ATUS(:
1. 7 reservoir for the dissolution medium.
2. 7 pump that forces the dissolution medium upwards through the flow-through
cell.
. 7 flow trough cell of transparent material mounted vertically with a filter
system preventing escape of un dissolved particles.
!. 7 water bath that will maintain the dissolution medium at &." to -." degree.
&ETOD:
Introduce the stated volume of the dissolution medium$ free from dissolved air$ into the
vessel of the apparatus. >arm the dissolution medium to between &." to -." degree.
=nless otherwise stated use one tablet or capsule. >hen the 7pparatus 1 is used$ place
the tablet or capsule in a dry basket at the beginning of each test. 6ower the basket into
position before rotation. >hen 7pparatus 2 is used$ allow the tablet or capsule to sink
to the bottom of the vessel prior to rotation of the paddle. 7 suitable devise such as a
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wire or glass helix is used to keep tablets or capsules that would otherwise float
hori5ontal at the bottom of the vessel. 9are should be taken to ensure that air bubbles
are excluded from the surface of the tablet or capsule. 2perate the apparatus
immediately at the speed of rotation specified in the individual monograph. >hen
7pparatus is used$ place glass beads of suitable si5e$ preferably ,./ to 1.1 mm in
diameter$ with one bead of !." to "." mm in diameter at the bottom of the cone to
protect the fluid entry of the tube and introduce the tablet or capsule in the cell or
within the layer of glass beads or capsule in the cell on or within the layer of glass
beads or by means of a holder. 7ssemble the filter head and fix the parts together by
means of a suitable clamping device. >arm the dissolution medium to between &."
and -." degree and introduce it through the bottom of the cell using a suitable pump to
obtain a suitable continuous flow at the specified rate AF"EB.
Take sample at !" minutes or at the prescribed intervals or continuously. >ithdraw the
sample from a point half-way between the surface of the dissolution medium and the
top of the rotating basket or blade. ;ot less than 1,, mm from the wall of the vessel$ or
from the continuously flowing medium of the flow-through cell. :xcept in the cases of
continuous flow with the paddle or basket method$ where the li%uid removed is
returned to the dissolution vessel$ and single sampling$ add a volume of dissolution
medium e%ual to the volume of sample withdrawn or compensate by calculation. @ilter
the samples at &." to -." degree and determine the amount of the active ingredient
present by the method prescribed in the individual monograph. The filter used is inert$
causes no significant absorption of the active ingredient from the solution$ contains no
materials extractable by the dissolution medium that would interfere analytical
procedures and has an appropriate pore si5e.
<epeat the complete operation five times. >here one tablet or capsule is directed to be
placed in the apparatus$ for each of the six tablets or capsules tested the amount of$
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active ingredient in solution is not less than -,E of the prescribed or stated amount$
unless otherwise specified in the monograph$ except that if one fails this re%uirement a
further six may be tested individually and all must comply. >here two or more tablets
or capsules are directed to be placed together in the apparatus$ a total of six replicated
test are carried out. In each test the amount of active ingredient in solution per tablet or
capsule is not less than -,E of the prescribed or stated amount$ unless otherwise stated
amount$ unless otherwise specified in the monograph. ;o retesting is permitted. >here
capsule shells interfere with the analysis$ remove the content of no fewer than six
capsules as completely as possible and dissolve the empty capsule shell in the specified
volume of the dissolution medium. 9arry out the test as directed in the individual
monograph and make any necessary correction. 9orrection factors should not be greater
than 2"E of the labeled content.
U#ITED3STATE PA%&ACOPIEAL %E2UI%&E#TS:
DISI#TE$%ATIO#:
This test is provided to determine compliance with the limits on the 1isintegration
stated in the individual monograph except where the label states that tablets or capsules
are intended for use as troches$ or are to be chewed$ or are designed as modified-release
dosage forms. 1etermine the type of units under test from the labeling and form
observation$ and apply the appropriate procedure to & or more dosage units.
@or the purpose of this test$ disintegration does not imply complete solution of the unit
or even of its active constituent. 9omplete disintegration is defined as that state in
which any residue of the unit. :xcept fragments of insoluble coating or capsule shell$
remaining on the screen of the test apparatus is a soft mass having no palpably core.
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APPA%ATUS:
The apparatus consist of a basket-rack assembly$ a 1,,,-ml$ low-from beaker$ 1+ to
1"" mm in height and having an inside diameter of /- to 11, mm for the immersion
fluid$ a thermostatic arrangement for heating the fluid between " to / degree$ and a
device for raising and lowering the basket in the immersion fluid at a constant
fre%uency rate between 2/ to 2 cycles per minute through a distance of not less than
". cm and not more than ".- cm. The volume of the fluid in the vessel in such that at
the highest point of the upwards stroke the wire mesh remains at least 2." cm below the
surface of the fluid and descends to not less than 2." cm from the bottom of vessel on
the downward stroke. The time re%uired for the upward stroke is e%ual to the time
re%uired for the downward stroke$ and the change in stroke direction is a smooth
transition$ rather than an abrupt reversal of motion. The basket-rack assembly moves
vertically along its axis. There is no appreciable hori5ontal motion or movement of the
axis from the vertical.
-AS7ET3%AC7 ASSE&-L9:
The basket-rack assembly consist of six open-ended transparent tubes$ each -.-"F ,.2"
cm long and having an inside diameter of 2,.- to2 mm and a wall 1., to 2.+ mm thick8
the tubes are held in a vertical position by two plastic plates+ :ach +.+ to /.2 cm in
diameter and " to - mm in thickness$ with six holes$ each 22 to 2& mm in diameter$
e%uidistant from the centre of the plate and e%ually spaced from one another. 7ttached
to the under surface of the lower plate is a woven stainless steal wire cloth$ with has a
plain s%uare weave with 1.+ to 2.2 mm mesh aperture and with a wire diameter of ,.&
F ,., mm. The parts of the apparatus are assembled and rigidly held by means of three
bolts passing through the two plastic plates. 7 suitable means is provided to suspend the
basket-rack assembly from the raising and lowering device using a point on its axis.
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The design of the basket-rack assembly may be varied somewhat provided the
specifications for the glass tubes and the screen mesh si5e are made.
DIS7S:
The use of disks is permitted only where specified in the monograph. If specified in the
individual monograph$ each tube is provided with a cylindrical disk /."F ,.1" mm thick
and 2,.- F ,.1" mm in diameter. The disk is made of a suitable$ transparent plastic
material having a specific gravity of between 1.1+ and 1.2,. @ive parallel 2 mm holes
extend between the ends of the cylinder. 2ne of the holes is centered on the cylindrical
axis. The other holes are centered &mm from the axis on imaginary line perpendicular
to the axis and parallel to each other. @our identical trape5oidal shaped planes are cut
into the wall of the cylinder$ nearly perpendicular to the end of the cylinder. The
trape5oidal shape is symmetrical its parallel sides coincide with the ends of the
cylinder. The trape5oidal shape is symmetrical its parallel sides coincide with the ends
of the cylinder and are parallel to an imaginary line connecting the centers of two
ad4acent holes & mm from the cylindrical axis. The parallel side of the trape5oid on the
bottom of the cylinder has a length of 1.& mm$ and its center lies at a depth of 1.+ mm
from the cylinders circumference. The parallel side of the trape5oid on the top of the
cylinder has a length of /.! F ,.2 mm$ and its center lies at a depth of 2.& F ,.1 mm
from the cylinder circumference. 7ll surfaces of the disk are smooth. If the use of disk
is specified in the individual monograph$ add a disk to each tube$ and operate the
apparatus as directed under procedure.
P%OCEDU%E:
U#COATED TA-LETS:
#lace 1 tablet in each of the six tubes of the basket and operate the apparatus$ using
water maintained at - F 2 degree as the immersion fluid unless otherwise specified in
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the individual monograph. 7t the end of the time limit specified in the monograph lift
the monograph lift the basket from the fluid and observes the tablets8 all of the tablets
have disintegrated completely. If 1 or 2 tablets fail to disintegrate completely$ repeat the
test on 12 additional tablets8 not less than of the 1+ tablets tested disintegrate
completely.
PLAI#3COATED TA-LETS:
7pply the test for uncoated tablets$ operating the apparatus for the time specified in the
individual monograph.
DELA9ED3%ELEASE *E#TE%IC COATED( TA-LETS:
#lace 1 tablet in ach 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 " minutes. Then
operate the apparatus using simulated gastric fluid maintained at -F2 as the immersion
fluid. 7fter 1 hr of operation in simulated gastric fluid T0$ lift the basket from the fluid
and observe the tablets: the tablet show no evidence of disintegration$ cracking$ or
softening. 2perate the apparatus$ using simulated intestinal fluid T0 maintained$
cracking$ or softening. 2perate the apparatus$ using simulated intestinal fluid T0
maintained at -F2 as the immersion fluid for the time specified in the monograph. 6ift
the basket from the fluid and observe the tablets: all of the tablets disintegrate
completely. If 1 or 2 tablets fail to disintegrate completely$ repeat the test on 1
additional tablet: not less than 1& of the total + tablets tested disintegrate completely.
-UCCAL TA-LETS:
7pply the test for uncoated tablets. 7fter ! hrs$ lift the basket from the fluid$ and
observe the tablets8 all of the tablets have disintegrated. If 1 or 2 tablets fail to
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disintegrate completely$ repeat the test on 12 additional tablets: not less than 1& of the
total l+ tablets tested disintegrate completely.
SU-3LI#$UAL TA-LETS:
7pply the test for uncoated tablets. 2bserve the tablets within the time limit specified
in the individual monograph: all of the tablets. 2bserve the tablets have disintegrated. If
1 or 2 tablets fail to disintegrate completely$ repeat the test on 12 additional tablets: not
less than 1& of the total of 1+ tablets tested disintegrate completely.
A%D $ELATI# CAPSULES:
7pply the test for uncoated tablet. 7ttach a removable wire cloth$ with has a pain
s%uare weave with 1.+ to 2.2 mm mesh aperture and with a wire diameter of ,.&, to
,.&"" mm$ as describe under basket-rack assembly$ to the surface of the upper plate of
the basket-rack assembly. 2bserve the capsules within the time limit specified in the
individual monograph: all of the capsules have disintegrated except for fragments from
the capsule shell. If 1 or 2 capsules fail to disintegrate completely$ repeat the test on 12
additional capsules: not less than 1& of the total of 1+ capsules tested disintegrate
completely.
SO"T $ELATI# CAPSULES:
#roceed as directed under hard gelatin 9apsules.
DISSOLUTIO#:
This test is provided to determine compliance with the dissolution re%uirements where
stated in the individual monograph for a tablet or capsule dosage form. 2f the types of
apparatus described herein$ use some specified in the individual monograph. >here the
tablets states an article is enteric coated$ and a dissolution or disintegration test does not
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specifically state that it is to be applied to enteric-coated is included in the individual
monograph$ the test for delayed articles under drug release is applied unless otherwise
specified in the individual monograph.
APPA%ATUS 0:
=se the assembly from apparatus1$ except that a paddle formed from a blade and a
shaft is used as the stirring element. The shaft is positioned so that its axis is not more
than 2 mm at any point from the vertical axis of the vessel and rotates smoothly without
significant wobble. The vertical center line of the blade passes through the axis of the
shaft so that the bottom of the blade is flush with the bottom of the shaft. The paddle
conforms to the specification shown in the fig 2. The distance of 2"F2 mm between the
blade and the inside bottom of the vessel is maintained during the test. The metallic or
suitably inert$ rigid blade and shaft comprise single entity. 7 suitable two-part
detachable design may be used provided the assembly remains firmly engaged during
the test. The paddle blade and shaft may be coated with a suitable inert coating. The
dosage unit is allowed to sink to the bottom of the vessel before rotation of the blade is
started. 7 small$ loose piece of noncreative material such as not more than a few turns
of wire helix may be attached to dosage unit that would otherwise float. 2ther validated
sinker devices may be used.
APPA%ATUS SUITA-ILIT9 TEST:
Individual test 1 tablet of the =0# 1issolution 9alibrator$ 1isintegration Type and 1
tablet of =0# 1issolution calibrator$ ;o disintegrating type$ according to the operating
conditions specified. The apparatus is suitable if the results obtained are within the
acceptable range stated in the certificate for the calibrator in the apparatus tested.
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DISSOLUTIO# &EDIU&:
=se the solvent specified in the individual monograph. If the dissolution medium is a
buffered solution$ ad4ust the solution so that its pD is within ,.," unit of the pD
specified in the individual monograph.
TI&E:
>here a single time specification is given$ the test may be concluded in a shorter period
if the re%uirement for minimum amount dissolved is met. If two or more times are
specified$ specimens are to be withdrawn only at the stated times$ within a tolerance of
F2E.
P%OCEDU%E "O% CAPSULES: U#COATED TA-LETS: A#D
PLAI# COATED TA-ETS:
#laced the stated volume of the dissolution medium in the vessel of the apparatus
specified in the individual monograph$ assembly the apparatus$ e%uilibrate the
1issolution medium to -F,." degree$ and remove the thermometer. #lace 1 tablet or 1
capsule in the apparatus$ taking care to exclude air bubbles from the surface of the
dosage .from unit$ 7nd immediately operate thus apparatus at the rate specified in the
individual monograph. >ithin the time interval specified$ or at each of the times stated$
withdraw a specimen from a 5one midway between the sure face of the dissolution
medium and the top of the rotating basket or blade$ not less than 1 cm from the vessel
wall. H#OTE: <eplace the ali%uots withdrawn for analysis with e%ual volume of fresh
dissolution medium at - degree or$ where it can be shown that replacement of the
medium is not necessary$ correct for the volume change in the calculation. Ieep the
vessel covered for the duration of the test$ and verify the temperature of the mixture
under test at suitable timesJ perform the analysis as directed in the individual
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monograph. <epeat the test with additional dosage form units. If automated e%uipment
is used for sampling and the apparatus is modified$ validation of the modified apparatus
is needs to show that there is no change in the agitation characteristics of the test.
>here capsule shells interfere with the analysis$ remove the contents of not less than &
capsules as completely possible$ and dissolve the empty capsule shells in the specified
volume of the dissolution medium. #erform the analysis as directed in the individual
monograph. ?ake any necessary correction. 9orrection factor greater than 2"E of the
labeled content is unacceptable.
P%OCEDU%E "O% A POOLED SA&PLE "O% CAPSULES:
U#COATED TA-LETS A#D COATED TA-LETS
=se this procedure where procedure for a pooled sample is specified in the individual
monograph. #roceed as directed under procedure for capsules$ uncoated tablets and
plain coated tablets. 9ombine e%ual volumes of the filtered solution of the six or twelve
individual specimen withdrawn$ and use the pooled sample as the test solution.
1etermine the average amount of the ingredient dissolved in the pooled sample.
I#TE%P%ETATIO#
=nit sample until unless specified in the individual monograph$ the re%uirements are
format if the %uantities of active ingredient dissolved from the units tested conformed
to the accompanying 7cceptance table. 9ontinue the testing through the three stages
unless the results conform at either 01 or 02. The %uantity$ K$ is the amount of
dissolved active ingredient specified in the individual monograph expressed as the
percentage of the labeled content8 the " E$ 1"E$ and 2"E values in the acceptance
table are percentages of the labeled content so that these values and K are in the same
terms.
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A7cceptance table written aboveB
POOLED SA&PLE
=nless otherwise specified in the individual monograph$ the re%uirements are met if the
%uantities of the active ingredient dissolved from the pooled sample. 9ontinue testing
through the three stages unless the results conform at either 01 or 02. The %uantity K is
the amount of dissolved active ingredient specified in the individual monograph$
expressed as a percentage of the labeled content.
ACCEPTA#CE TA-LE "O% POOLED SA&PLE
Stage #umber Tested Acce!tance Criteria
01 &
7verage amount dissolved is not
less than KF 1,E
02 &
7verage amount dissolved
A01F02B is e%ual to or
greater than KF"E
0 12
7verage amount dissolved
A01F02F0B is e%ual to greater
than K.
D%U$ %ELEASE
This test is provided to determine compliance with drug release re%uirements where
specified in the individual monograph. =se the apparatus specified in the individual
monograph. <eplace the ali%uots withdrawn for analysis with e%ual volume of fresh
dissolution medium at -L or where it can be shown that replacement of the medium is
not necessary$ correct the volume change in the calculation. H;2T:: medium
replacement is not necessary for apparatus !$ which is continuous flow systemJ Ieep
the vessel covered for the duration of the test$ and verify the temperature of the mixture
under test at suitable times.
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E;TE#DED %ELEASE A%TICLES3$E#E%AL D%U$ %ELEASE
STA#DA%D:
APPA%ATUS ' A#D APPA%ATUS 0:
APPA%ATUS: proceed as directed under dissolution.
APPPA%ATUS SUITA-ILIT9 TEST: DISSOLUTIO# &EDIU&:
A#D P%OCEDU%E:
#roceed as directed under dissolution.
TI&E:
The test time points$ generally three are expressed in hours. 0pecimens are to be
withdrawn within a tolerance of F2E of the stated time.
I#TE%P%ETATIO#:
%uantities of the active ingredient dissolved from the units tested conform to acceptance
table 1. 9ontinue testing through the three levels unless the results conform at either 61
or 62. 6imits on the amount of the active ingredient dissolved are expressed in terms of
the percentage of labeled content. The limit embrace each value of K$ the amount
dissolved at each specified fractional dosing interval. >here more than one range is
specified in the individual monograph$ the acceptance criteria apply individually to
each range.
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ACCEPTA#CE TA-LE
LE5EL #U&-E%
TESTED
C%ITE%IA
61 &
;o individual value lies outside each of
the staged ranges and no individual value
is less than the stated amount at the final
test time.
62 &
The average value toCf the 12
unitsA 61F62B lies within each of the
stated ranges and is not less than the stated
amount at the final test time8 none is more
than 1,E of the labeled content below the
state test time.
6 12
The average value of the 2! units
A61F62F6B lies within each of the stated
ranges$ and is not less than the stated
amount at the final test time: not more
than 2 of the 2! units are more than 1, E
of the labeled content below the stated
amount at the final test time: and none of
the units is more than 2,E of labeled
content outside each of the stated ranges
or more than 2,E of the labeled content
below the stated amount at the final test
time.
APPA%ATUS 1 *%ECIP%OCATI#$ C9LI#DE%(
APPA%ATUS:
The assembly consist of the set of cylindrical$ flat bottomed glass vessel8 a set of glass
reciprocating cylinder8 stainless steel fittings Atype 1& or e%uivalentB and screens that
are made of suitable nonsorbing and no reactive material and that are designed to fit the
tops and bottoms of the reciprocating cylinders: and a motor and drive assembly to
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reciprocate the cylinders vertically inside the vessel and$ if desired$ index the
reciprocating cylinders hori5ontally to a different row of vessel. The vessels are
partially immersed in a suitable water bath of any convenient si5e that permits the
holding the temperature at -M,."Lc during the test no part of the assembly including
the environment in which the assembly is placed$ contributed significant motion$
agitation$ or vibration beyond that due to the smooth$ vertically reciprocating cylinder.
7 device is used that allows the reciprocation rate to dCbe selected and maintained at the
dip rate specified in the individual monograph$ within M"E. 7n apparatus that permits
observations of the specimens and reciprocating cylinders is preferable. The
components conform to the dimensions shown in the figure unless otherwise specified
in the individual monograph.
APPA%ATUS SUITA-ILIT9 TEST:
Individual test 1 tablet of the =0# release calibrator tablets Asingle unitB and a specified
amount content of the =0# drug release calibrator beads Amultiple unitB leading to the
operation conditions specified. The apparatus is suitable for the results obtained are
within the acceptable range stated in the certificate for that calibrator in the apparatus
tested.
DISSOLUTIO# &EDIU&:
P%OCEDU%E:
#lace the stated volume of the dissolution medium in vessel of the apparatus$ assemble
the apparatus$ e%uilibrate the dissolution medium to -M"Lc and remove the
thermometer. #lace dosage form unit in each of the & reciprocating cylinders$ taking to
exclude air bubble from the surface of each dosage form unit$ immediately operate the
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apparatus as specified in the individual monograph. 1uring the upward and down word
stroke$ the reciprocating cylinder moves through a total distance of /./ to 1,.1 cm.
within time interval specified$ or at each time stated$ raise the reciprocating cylinder
and withdraw a portion of the solution under form a 5one midway between the surface
of the dissolution medium and the bottom of each vessel. #erform the analysis as direct
under individual monograph. If necessary repeat the test with additional dosage form
units.
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APPA%ATUS < *"LO8 T%OU$ CELL(:
APPA%ATUS:
The assembly consists of a reservoir and a pump for dissolution medium: a flow
through cell8 a water bath that maintain dissolution medium at -M,."Lc. the procedure
is specified in the individual monograph.
The pump forces the dissolution medium upwards to the flow through cell. The pump
has a delivery range between 2!, and /&, ml per hour$ with standard flow rates of !$ +$
and 1& ml per minute. It must be volumetric to deliver constant flow independent of
flow resistance in the filter device8 the flow profile is sinusoidal with a pulsation of
12,M1, pulse per minute.
The flow through cell of inert and transparent material$ is mounted vertically with filter
system that prevent the escape of undisclosed particles from the top of the cell8 standard
cell diameter are 12 and 22.& mm8 the bottom cone is usually filled with small glass
beads of about 1 mm diameter with 1 bead of about " mm positioned at the apex to
available for positioning the special dosage form$ for example inlay tablets. The cell is
immersed in the water bath and the temperature is maintained at -M,."Lc.
The apparatus uses a clamp mechanism and two 2-rings for the fixation of the cell
assembly. The pump is separated from the dissolution unit in order to shield the latter
against any vibration originating from the pump. The position of the pump should not
be on a level higher than a reservoir flask. Tube connections are as short as possible.
=se polite tubing with a 1.& mm inner diameter and chemically inert flanged end
connections.
APPA%ATUS SUITA-ILIT9 TEST A#D DISSOLUTIO# &EDIU&:
P%OCEDU%E:
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_________________________________________________________ References
#lace the glass beads into the cell specified in the monograph. #lace 1 dosage form unit
on the top of the beads or if specified in the monograph on a wire carrier. 7ssemble the
filter helix and fix the part together by means of suitable clamping device. Introduce by
the pump dissolution medium warmed to -M"L through the bottom of the cell to obtain
the flow rate specified in the individual monograph and measured with accuracy.
9ollect the elute by fractions at each of the time stated. #erform the analysis as directed
in the individual monograph.
>here capsule shells interfere with the analysis$ remove the contents of not less than &
capsules as completely as possible$ and dissolve the empty capsule shells in the
specified volume of dissolution medium.
TI&E A#D I#TE%P%ETATIO#:
#roceed as directed under apparatus 1 and 2.
DELA9ED3%ELEASE *E#TE%IC COATED( A%TICLES3
$E#E%AL D%U$ %ELEASE STA#DA%D:
=se ?ethod 7 or ?ethod 3 and the apparatus specified in the individual monograph.
9onduct the apparatus suitability test as directed under dissolution. 7ll test ties stated
are to be observed within a tolerance of M2E$ unless otherwise specified.
&ETOD A:
P%OCEDU%E: *Unless ot)er,ise directed in t)e individual
monogra!)(
ACID STA$E:
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_________________________________________________________ References
#lace -", ml of ,.1; D9l in the vessel$ and assemble the apparatus. 7llow the medium
to e%uilibrate to a temperature of -M,."Lc. #lace 1 tablet or 1 capsule in the apparatus$
cover the vessel and operate the apparatus for 2 hours at the rate specified in the
monograph.
7fter 2 hours of the operation in ,.1; D9l$ withdraw an ali%uot of the fluid and
proceed immediately as directed for the buffer stage.
#erform the analysis of the ali%uot using the procedure specified in the test for drug
release in the individual monograph.
=nless otherwise specified in the individual monograph$ the re%uirements of this
portion of the test are met if the %uantities$ based on the E labeled content$ of active
ingredient dissolved from the units tested conform to acceptance table 2. 9ontinue
testing through all levels unless the results of both acid and buffer stages conform at an
earlier level.
ACCEPTA#CE TA-LE 0:
LE5EL #U&-E% TESTED C%ITE%IA
71 & ;o individual value exceeds 1,E dissolved
72 &
7verage of the 12 units A71F72B is not more
than 1,E dissolved$ and no individual unit is
greater than 2"E dissolved.
7 12
7verage of the 2! units A71F72F7B is not
more than 1,E dissolved$ and no individual unit
is greater than 2"E dissolved.
-U""E% STA$E:
>ith the apparatus operating at the rate specified in the monograph$ add to the fluid in
the vessel 2", ml of ,.2,? tri basic sodium phosphate that has been e%uilibrated to
-M,."Lc. 7d4ust if necessary with 2 ; sodium hydroxide to a pD of &.+M,.,". 9ontinue
to operate the apparatus for !" minutes$ or for the time specified in the individual
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_________________________________________________________ References
monograph. 7t the end of the time period$ withdraw an ali%uot of the fluid. 7nd
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 period of time that
specified for the buffer stage if the re%uirement for minimum amount is dissolved is
met an earlier time.
I#TE%P%ETATIO#:
%uantities of the active ingredient from the units tested conform to acceptance table .
9ontinue testing through the three levels the results of both stages conform at an earlier
level. The value of K in acceptance table is -"E dissolved unless otherwise specified
in the individual monograph. The %uantity$ K$ specified in the individual monograph$ is
the total amount of active ingredient dissolved in both the buffer stages$ expressed as a
percentage of the labeled content so that these values and K are in the same terms.
ACCEPTA#CE TA-LE 1:
31 & :ach unit is not less than KM"E
32 &
7verage of 12 units A31F32B is e%ual to or
greater than K$ and no unit is less than K-1"E
3 12
7verage of 2! units A31F32F3B is e%ual to or
greater than K$ not more than two units are less
than K-1"E and no unit is less than K-2"E
&ETOD -:
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_________________________________________________________ References
P%OCEDU%E: *unless ot)er,ise directed in t)e individual
monogra!)(
ACID STA$E:
#lace 1,,, ml of ,.1 ; D9l in the vessel$ and assemble the apparatus. 7llow the
medium to e%uilibrate to a temperature of -M,." Lc. #lace 1 tablet or 1 capsule in the
apparatus$ cover the vessel$ and operate the apparatus for 2 hours at the rate specified in
the monograph. 7fter 2 hours of operation in ,.1 ; D9l$ withdraw an ali%uot of the
fluid$ and proceed immediately as directed under buffer stage.
#erform an analysis of the ali%uot using the procedure specified in the test for drug
release in the individual monograph.
=nless otherwise specified in the individual monograph$ the re%uirement of this portion
of the test are met if the %uantities$ based on the E of the labeled content of active
ingredient dissolved from the units tested conform to acceptance table 2 under method
7. continue testing through all levels unless the results of both acid and stage conform
at an earlier level.
3=@@:< 0T7N::
;2T:: for this stage procedure$ use buffer that previously has been e%uilibrated to a
temperature of -M,." Lc.
1rain the acid from the vessel and add to the vessel 1,,, ml of pD &.+ phosphate
buffer$ prepared by mixing ,.1 ; D9l with ,.2, ? tribasic sodium phosphate A:1B and
ad4usting$ if necessary$ with 2 ; D9l or 2 ; ;a2D to a pD of &.+M,.,". 9ontinue to
operate the apparatus for !" minutes or for the time specified in the individual
monograph. 7t the end of the time period$ withdraw an ali%uot 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 the shorter period than that specified for the
buffer stage if the re%uirement for the minimum amount is dissolved met an earlier
time.
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_________________________________________________________ References
I#TE%P%ETATIO#:
#roceed as directed for interpretation under method 7.
T%A#SDE%&AL DELI5E%9 S9ESTE&3 $E#E%AL D%U$
%ELEASE STA#DA%DS:
APPA%ATUS = *PADDLE O5E% DISC(
APPA%ATUS:
=se the paddle and vessel assembly for the apparatus 2 as describe under dissolution$
with the addition of the stainless steel disc assembly designed for holding the transferal
system at the bottom of the vessel other appropriate devices may be used provided they
do not sorbs$ react with$ or interfere with specimen being tested. The temperature is
maintained at -M,."Lc. 7 distance of 2"M2 mm between the paddle blade and the
surface of the disc assembly is maintained during the test. The vessel may be covered
during the test to minimi5e the evaporation. The disk assembly for holding the
transferal system is designed to minimi5e any 'dead( volume between 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 paddle blade.
APPA%ATUS SUITA-IT9 TEST A#D DISSOLUTIO# &EDIU&:
#roceed as directed for apparatus 2 under dissolution.
P%OCEDU%E:
#lace the stated volume of the dissolution medium in the vessel$ assemble the apparatus
without disk assembly$ and e%uilibrate the medium to -M,." Lc. apply the transdermal
system to three disk assembly$ assuring that the release surface of the system is as flat
as possible. The system is attached to the disk by applying a suitable adhesive to the
disk assembly. 1ry for 1 minute. #ress the system release the surface side up$ onto the
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_________________________________________________________ References
adhesive coated side of the disk assembly. If a membrane is used to support the system$
it is applied so that no air bubble should occur between the membrane and the release
surface. #lace the disk assembly flat at the bottom of the vessel with release surface
facing up and to the parallel edge of the paddle is 2"M2 mm from the surface of the
dissolution medium. The bottom edge of the paddle is 2"M2 mm from the surface of the
disk assembly. Immediately operate the apparatus at the rate specified in the
monograph. 7t each sampling time interval$ withdraw a specimen from a 5one midway
between the surface of the dissolution medium and the top of the blade$ not less than 1
cm from the vessel wall. #erform the analysis on each sample ali%uots as directed in the
individual monograph$ correcting for any volume losses$ are necessary. <epeat the test
with additional transferal systems.
TI&E:
The test point generally three$ is expressed in hours. 0pecimens are to be withdrawn
within a tolerance of F1" minutes or F2 E of the stated time$ the tolerance that results
in the narrowest time interval being selected.
I#TE%P%ETATIO#:
%uantities of the active ingredients released from the system conform to the 7cceptance
table ! for transferal drug delivery system. 9ontinue testing through the three levels
unless the results conform at either 61 or 62.
ACCEPTA#CE TA-LE <:
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_________________________________________________________ References
61 &
;o individual value lies outside the stated
range.
62 &
The average values of 12 units A61F62B lie
within the stated range. ;o individual value is
outside the stated range by more than 1,E of
the average of the stated range.
6
12
The average value of the 2! units
A61F62F6B lies within the stated range. ;o
of the 2 of the 2! units are outside the stated
range by more than 1, E of the stated range
and none of the units is outside the stated
range by more than 2,E of the average of the
stated range.
APPA%ATUS > *C9LI#DE%(:
APPA%ATUS:
=se the vessel assembly from the apparatus 1 as described under dissolution$ except to
replace the basket and shaft with the stainless steel cylinder stirring element and to
maintain the temperature at 2M,." Lc during the shaft and the cylinder components of
the stirring elements are fabricated of stainless steel to specifications. The dosage unit
is placed on the cylinder at the beginning of the each test. The distance between the
inside bottom of the vessel and the cylinder is maintained at 2"M2 mm during the test.
DISSOLUTIO# &EDIU&:
=se the medium specified in the individual monograph.
P%OCEDU%E:
_________________________________________________________ References
#lace the stated volume of the dissolution medium in the vessel of the apparatus
specified in the individual monograph$ assemble the apparatus and e%uilibrate the
dissolution medium to ,." Lc. =nless otherwise directed in the individual monograph
prepares the test system prior to test as follows. <emove the protective li%uor from the
system and place the adhesive side on the piece of cuprophan that is not less than 1 cm
larger on all sides than a system. #lace the system cuprophan covered side down$ on a
clean surface$ and apply a suitable adhesive to the exposed cuprophan borders. If
necessary apply additional coated adhesive side of the system to the exterior of the
cylinder such that the long axis of the system fits around the circumference of the
cylinder. #ress the cylinder in the apparatus and immediately rotate at the rate specified
in the individual monograph. >ithin the interval specified or each of the times stated$
withdraw a %uantity of dissolution medium for analysis of a top of the rotating cylinder$
not less than 1 cm from the vessel wall. #erform the analysis as directed in the
individual monograph$ correcting for any volume losses as necessary. <epeat the test
with transferal drug delivery system.
TI&E:
#roceed as directed under apparatus .
I#TE%P%ETATIO#:
%uantities of active ingredient released from the system conform to acceptance table !
for transferal drug delivery system. 9ontinue the testing through the three levels unless
the results conform at either 61 or 62.
APPA%ATUS ? *%ECIP%OCATI#$ C9LI#DE%(
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_________________________________________________________ References
#OTE: T)is a!!aratus ma6 also be s!ecified for use ,it) a variet6 of dosage
forms.
APPA%ATUS:
The assembly consists of a set of volumetrically calibrated or tarred solution container
made of glass or suitable inert material$ a motor and drive assembly to reciprocate the
system vertically and to index the system hori5ontally to a different row of vessels
automatically if desired$ and set of suitable sample holders. The solution containers are
partially immersed in a suitable water bath of any convenient si5e that permits
maintaining the temperature T$ inside the containers at -M,."Lc or within the allowable
range. 7s specified in the individual monograph during the test. ;o part of the
assemble$ including the environment in which assembly is placed$ contribute significant
motion$ agitation or vibration beyond that due to smooth$ vertically reciprocating
sample holder.
DISSOLUTIO# &EDIU&:
=se the dissolution medium specified in the individual monograph.
P%OCEDU%E:
0uspend each sample holder from a vertically reciprocating shaker such that each
system is continuously immersed in an accurately measured volume of dissolution
medium within an e%uilibrated container pre-e%uilibrated to temperature$ T. reciprocate
at a fre%uency of , cycles per minute with an amplitude of about 2 cm$ or as specified
in the individual monograph$ for the specified time into the medium specified for each
time point. <emove the solution containers from the bath$ cool to room temperature and
add sufficient solution to correct the evaporative loss. #erform the analysis as directed
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_________________________________________________________ References
in the individual monograph. <epeat the test with additional drug delivery system as
re%uired in the individual monograph.
I#TE%P%ETATIO#:
%uantities of active ingredient released from the system conform to acceptance table !
for coated tablet drug delivery system. 9ontinue the testing through the three levels
unless the results conform at either 61 or 62.
)var)www)apps)conversion)tmp)scratch*1)2+,+++!1.doc "&
_________________________________________________________ References
1. The science and practice of pharmacy 2,
th
edition.
2. #harmaceutical dosages form.tablets volume 2$2
nd
edition by D.7. 6ieberman and
6-6echman
. #harmaceutical dosage form-capsules$ volumes 2$2
nd
edition by D.7. 6ieberman
and 6-6ibra am
!. 1ispensing pharmacy by N.I. Oanis
". #harmaceutics the science of dosage form design by ?.:. 7=6T2;.
&. :ncyclopedia of pharmaceutical technology 2
nd
edition volume
-. 9omprehensive pharmacy review "
th
:dition by loen shargel.
+. Theory and practice of industrial pharmacy$
rd
edition by 6eon 6echman.
/. 9opper and ginPs dispensing for pharmaceutical student 12
th
:dition by 0.O.9arter.
1,. #harmaceutical dosage form and drug delivery system$ -
th
edition by Doward
9. 7nseal.
11. 3ritish pharmacopeias -2,,1$ volume 1 and volume 2
12. =nited state pharmacopeias national formulary 2,, $ 7sian edition
1. Indian pharmacopeias 1//&
1!. 2ral drug absorption prediction and asseement by Oennifer 3.1ressman.
1". 1rug and pharmaceutical science$ 2
nd
:dition$ volume &- by N >elling francs
6.0.Tse.
1&. 2ral drugs absorption drugs and pharmaceutical science by dress mar.
1-. 1avies b and monist physiological parameter in laboratory animal and human.
1+. #harmacopeias and formularies by Darkishan 0ingh.
1/. #harmaceutical dosage form and drug delivery system +
th
:dition by 6oyd Q. 7llen
and O.<.$ ;icholas.
2,. Dandbook of safe drug usage delivery by Q.<. 0henoy and 7.<. 0henoy.
21. Tutorial book of pharmaceutics by O.3ently.
22. ?odern dispensing by guad.
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_________________________________________________________ References
I#DE;
SR. NO. CONTENT PAGE. NO.
' Introduction
0 Classification
1 &onogra!)
< Standards
= A!!aratus
> %eferences
)var)www)apps)conversion)tmp)scratch*1)2+,+++!1.doc "+

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Oral solid Dosage forms

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