oral solid dosage forms
TRANSCRIPT
_________________________________________________________ _ 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.
3. They are the lightest and most compact of all oral dosage forms.
4. They are in general the easiest and the cheapest to package and ship of all oral
dosage forms.
5. Product identification is potentially the simplest and cheapest, requiring no
additional processing steps when employing and embossed or monogrammed
punch face.
6. 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
7. They lend themselves to certain special release profile product such as enteric or
delayed –release products.
8. They are better suited to large-scale production then other unit oral forms.
9. They have the best –combined properties of chemical, mechanical and
microbiologic stability of all the oral forms.
Disadvantages of Tablets:1. Some drugs resist compression in to dense compacts, owing to their amorphous
nature or flocculent, low density character.
2. Drugs with poor wetting, slow dissolution properties, intermediate to large
dosage. Optimum 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 adequate or full drugs bioavailability.
3. Bitter-testing drugs, drugs with an objective odor, or drugs that are sensitive to
oxygen or atmospheric moisture may require encapsulation or entrapment prior
to compression, or the tablet may require 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 sizes. Like
cachets they are useful for unpleasant medicaments.
1. Hard capsules are for solid medicaments. They consist of a cylindrical body
and cap. Both with hemispherical end, and are usually made from gelatin and
water with added preservative. Although quite hard, they soften readily and
dissolve after swallowing with water.
2. Soft capsules are for solids liquids 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.
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_________________________________________________________ _ Introduction
Advantages of Capsules:1. They obscure the taste and odor of unpleasant drugs.
2. They are attractive in appearance.
3. They are slippery when moist, and hence easy to swallow with a draught of
water.
4. If properly stored the shells contain 12-15 percent of moisture which gives
flexibility and, consequently, very considerable resistance to mechanical
stresses.
5. Less adjuncts are necessary than for tablets.
6. The contents are usually in fine powder, which combined with freedom or
near freedom from adjuncts, provides rapid and uniform release of
medicaments in the gastro-intestinal tract.
7. The shells can be pacified or colored, to gibe protection from light.
8. The shells are made to very fine limits; hence the cap and base fit well and
give substantial protection against air moisture.
9. The shells are physiologically inert and easily and quickly digested in the
gastrointestinal tract.
10. Presentation of a drug in capsules, rather then in tablets, allows quicker
submission of a new drug for clinical trials, because fewer development
problems are involved .also it is easier to vary the dose.
11. Complicated machinery is unnecessary for the extemporaneous dispensing
of a few capsules.
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_________________________________________________________ Monograph
CLASSIFICATION OF SOLID DOSAGE FORM1) As such (a) Oral
(i.) Divided powder
Simple powder Compound powder
(ii.) Bulk powder
Effervescent powder Antacid Laxatives Dietary
(B) External
Dusting powder Snuff Insufflations Sprays Aerosols Dentifrices
(C ) Parenterals
2) Compressed
Tablets Capsules Cachets
3) Moulded
Suppositories Tablet triturates Lozenges Pastilles Pills
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_________________________________________________________ Monograph
MONOGRAPH:
TABLETS
DEFINITION:
Tablets are solid dosage forms each containing a unit dose of one or more
medicaments.
INTRODUCTION:
They are intended for oral administration. Some 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. Preparation
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 required
special formulations, methods of manufacture or from of presentation appropriate to the
particular use they may not comply with all the requirement 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. Such substances
must be innocuous and therapeutically inert in the quantities present.
Because of their composition, method of manufacture or intended use, tablets present
variety of characteristics and consequently there are several categories of tablets.
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_________________________________________________________ Monograph
Useless otherwise stated in the individual monograph, tablets are uncoated. Where
coating is permitted the monograph directs coating the statement reads “The tablets are
coated “
Unless otherwise directed, tablets may be coated in one of different ways.
GENERAL CHARACTERSTICS:
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.
INDIAN PHARMACIA REQUIREMENTS:
UNCOATED TABLETS:
Uncoated 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 Any 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. Uncoated tablets
have the general characteristics of tablets. When 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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INDIAN PHARMACOPEIAL REQUIEMS
COATED TABLETS: Coated tablets are covers with one or more layers mixture of various substances such as
resins, gums, inactive, and insoluble fillers, sugars, plasticizes 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. When the coating is thin, the
tablets are described as a film coated. Coated tablets may contain flavoring and or one
or more coloring agents permitted under the drug and cosmetic rules 1945
Coated tablets have a smooth. Usually polished and after colored. Surface: a broken
sections examined under a lens shows a core surrounded by one or one more
continuous layers of a different texture.
BRITISH PHARMACOPEIAL REQUIREMENTS: DISINTEGRATION TESTS:
Coated tablets other than film-coated tablets comply the test for disintegration of tablets
and capsules use water R a liquids medium add a disc to each tube operate the
apparatus for 60 minuets unless otherwise justified and authorized and examine the
state of the tablets if any has not disintegrated repeats the test on a further six tablets
replacing water R which 0.1 M hydrochloric acid the tablets comply with the test if all
six tablets have disintegrated in the acid medium.
Film–coated tablets comply with the disintegration test pre cribbed over expect that the
apparatus is operated for 30 minute unless otherwise justified and authorized.
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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.
INDIAN PHARMACOPEIAL REQUIREMENTS:
ENTERIC-COATED TABLETS
Enteric –coated tablets (gastric –resistant tablets) 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. For this purpose substance such as acetate phthalate and anionic
copolymer of met acrylic acid and its ethers are used for providing tablets with a
gastric\-resistant coating to for covering either granules or particles with gastric –
resistant coating Enteric–coated tablets have the characteristics of coated tablets.
BRITISH PHARMACOPEIAL REQUIREMENTS:
PRODUCTION:
For tablets prepared form granules or particles already covered with a gastro-resistant
coating a Suitable test is carried out to demonstrate of the active substances
DISINTEGRATION TESTS:
For tablets wit a gastro-resistance coating carry out the test for disintegration with the
following modifications use 0.1 M hydrochloric acid. As the liquid medium operate the
apparatus for 2 hr or other such time as may be joisted and authorized 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 3 hr but even with
authorized deviations is not less than 1 hr No tablets show signs of either
disintegrations (apart from the fragment of coating ) or creaks that would that allow the
escape of the contents Replace the acid by phosphate buffer solution pH 6.8 R and a
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disc to each tube. Operate the apparatus for the 60 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 .
INDIAN PHARMACOPEIAL REQUIREMENTS:
DISINTEGRATION TESTS:
Dispersible tablets are uncoated tablets that procedure a uniform dispersion in water
and May contains permitted colorings and flavorings agents.
FINENESS OF DISPERSION:
Place two tablets in 100 ml of water R and stir completely dispersed a smooth
dispersion is produce which oases though a serve screen with a nominal mesh aperture
is procure of 710 micro meters.
INDIAN PHARMACOPEIAL REQUIREMENTS:
MODIFIED – RELEASE TABLETS:
Modified – release tablets (Sustained– releases tablets) 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.
BRITISH PHARMACOPEIAL REQUIREMENTS:
PRODUCTION:
A suitable test is carried out to demonstrate the appropriate release of the active
ingredients.
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INDIAN PHARMACOPEIAL REQUIREMENTS:
SOLUBLE TABLETS:
Soluble tablets are uncoated that dissolve in water. The solution may be slightly
opalescent due to added substances used in the manufacture of the tablets.
BRITISH PHARMACOPEIAL REQUIREMENTS:
DISITEGREATIUON TEASTS:
Soluble tablets disintegrate within 3 minutes when examined by the test for
disintegration of tablets and capsules, but water R at 15 to 25 degree C.
INDIAN PHARMACOPEIAL REQUIREMENTS:
EFFERVENCENT TABLETS:
Effervescent 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,
BRITISH PHARMACOPEIAL REQUIREMENTS:
DISITEGREATIUON TEASTS:
Place tablets in a breaker containing 200 ml of water R at 15 degree to 25 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. Repeat the oration on five other
tablets the comply with the if each of the six tablets used disintegrates in the manner
prescribed within 5 minutes, unless otherwise justified and authorized.
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TABLETS FOR USE IN THE MOUTH:
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 (lozenges) or the release and
absorption of the active ingredients under the tongue (sublingual tablets).
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STANDARDS:
Uniformity of container contents:
Tablets comply with the test for contents of packaged dosage forms, Appendix 11.2
CONTAENTS OF PACKGED DOSAGE FROMS:
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
quantity is not more than 100g or 300ml or 1000 units, as the case many be. For higher
labeled quantities the test and limit given in the stammered of weighing and measure
(Packaged commodities).
CONTENT OF THE ACTIVE INGREDIENT:
Determine the Amount 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 requirements that 20 tablets or such other numbers as may be indicated in there
monograph are used in the assay where 20 tablets cannot be obtained , a small number
which must not be less than 5 may be used but to allow for sampling errors the
tolerances are winded in accordance with table 1 the requirements of table 1 apply
when the stated limits are between 91 and 110% for the limits than 90 to 110%
proportionately smaller or larger allowances should be made
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Table-1
WEIGH OF ACTIVE INGREDIENTS IN EACH TABLETS
SUBTRACT FROM LOWER LIMIT OF SAMPLES
ADD TO THE UPPER LIMIT FOR SAMPLES OF
15 10 5 15 10 5
0.12g or less 0.2 0.7 1.6 0.3 0.8 1.8
More than 0.12 g but less 0.3 g
0.2 0.5 1.2 0.3 0.6 1.5
0.3 or more 0.1 0.2 0.8 0.2 0.4 1.0
UNIFORMITY OF WEIGHT:
This is not applicable to coated tablets other than film-coated to tablets that are required
to comply with the test for uniformity of content for all active ingredients.
Weight 20 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.
Table-2
AVERAGE WEIGHT OF TABLET PERCENTAGE DEVIATION
80 mg more less 10
More than 80mg but less than 250mg 7.5
250 mg or more 5
UNIFORMITY OF CONTENT:
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This test is applicable to tablets that contain less 10mg or less than 10% 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.
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.
Determine the content of the active ingredient in each of 10 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 75 to
125% repeat the determination using another 20 tablet the tablet comply with the test if
in individual values are outside the limit 85 to 115% and outside the limits 75 to 125 %
of the average value.
DISINTEGRATION:
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 Appendix 7.3 is
included in the individual monograph, the disintegration is not required.
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DISSOLUTION TEST FOR TABLETS AND CAPSULES:
Use apparatus 1 unless otherwise directed. All 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 316 or equivalents 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.
APPARATUS-1:
An assembly consisting of the following:
a. A cylinder vessel, A, made of borosilicate glass or any other
suitable transparent material, with a hemispherical bottom and with a nominal
capacity of 1000ml. the vessel has a flanged upper rim and is fitted with a lid
number of openings, one of which is central.
b. A motor with a speed regular capable of maintaining the speed of
rotation of the paddle within 4% of that specific in the individual monograph. The
motor is fitted with a stirring element. Which consists of a drive shaft and blade
forming a paddle, B 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 23 to 27 mm from the inside bottom of the vessel. The apparatus operates
in such a way that the paddle rotates smoothly and without significant wobble.
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c. A water-bath set to maintain the dissolution at 36.5 to 37.5
degree. The bath liquid 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 equipment. Including the water circulation device, is
minimized.
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APPARATUS-2:
The assembly is the same as in apparatus 1 expect that in the string element the paddle
is replaced by a basket, D (see 7.3-3 and 7.3-4) the metallic shaft rotates smoothly and
without significant wobble the top part with a vent is attached to the shaft C. 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 0.254 mm diameter and
wit 0.381 mm squire 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 2.5 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 23 to 27 mm during the test.
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DISSOLUTION MRDIUM:
Use the dissolution medium specified in the individual monograph. If, the medium is a
buffered solution, so that, its pH is within 0.05 units of the specified in the monograph.
The dissolution medium should be departed prior to testing.
TIME:
Where a single time specification is given in the monograph, the test may be concluded
in a shorter period if the requirement 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 +2%.
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METHOD:
Introduce the stated volume of the dissolution medium, free from dissolved air, into the
vessel of the apparatus. Warm the dissolution medium to between 36.5 and 37.5 degree.
Unless otherwise stated use one tablet or capsules.
When apparatus 1 is used, allow the tablet or capsule to sink to the bottom of the vessel
prior to rotation of the paddle. A suitable device such as a wire or glass helix may be
used to keep horizontal at the bottom of the vessel or capsules that would otherwise
float. Care should be taken to ensure that air bubbles excluded from the surface of the
tablet or capsule. When the apparatus 2 is used, place the tablet or capsule in a dry
basket at the beginning of each test. Lower the basket into a position before rotation.
Operate the apparatus immediately at the speed of rotation specified in the individual
monograph.
BRITISH PHARMACOPEIAL REQUIREMENTS:
Apparatus 3 is used, place glass beads of a suitable size, preferably 0.9 to 1.1 mm in
diameter, with one bead of 4.5 to 5.5 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. Assemble the filter based and
fix the parts together by means of a suitable clamping device. Warm the dissolution
medium to between 36.5 to 37.5 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 (+5%).
INDIAN PHARMACOPEIAL REQUIRMENTS:
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Within the time interval specified, or at each time stated, withdraw a specimen from a
zone midway between the surface of the dissolution medium and the top the rotating
blade or basket, not less than 10 mm from the wall of the vessel. Except in the case of
single sampling, add a volume of dissolution medium equal to the volume of the
sample withdrawn. Perform the analysis as directed in the individual monograph;
Repeat the whole operation five times. Where two or more tablets or capsules are
directed to be placed together in the apparatus, carry out six replicate tests.
For each of the tablet or capsule tested, calculate the amount of dissolved active
ingredients in the solution as a percentage of the stated amount. Where two or more
tablets or capsules are placed together, determine for each test the amount of active
ingredient in the solution. Per tablet or capsules and calculate as a percentage of the
stated amount. If the result do not confirm to the requirements at stage S1 given in the
accompanying acceptance table (table 1), continue testing with additional tablets or
capsules through stage S2 and S3 unless the result conform at stage S2.
Where the capsule shells interfere with the analysis, remove the contents of not less
than 6 capsules as completely as possible, and dissolve the empty capsule shells in the
specified volume of the dissolution medium. Perform the analysis as directed in the
individual monograph. Make any necessary correction. Correction factor should not be
greater than 25% of the stated amount.
TABLE 1-Acceptance Table
STAGE NUMBER TESTED
ACCEPTANCECRITERIA
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S1 6Each unit is not less thanD*+5%
S2 6Average of 12 units (S1+S2) is equal to or greater than D and no unit is less than D-15%.
S3 12
Average of 24 units (S1+S2+S3) is equal to or greater than D, not more than 2 units are less than D-15% and no unit is less than D-25%.
*D is the amount of dissolved active ingredient specified in the individual monograph.
Expressed as a percentage of the stated amount.
UNCOATED TABLETS:
Comply with the disintegration test for tablets and capsules, Appendix 7.1. Unless
otherwise directed in the individual, use water as the medium and add to each tube.
Operate the apparatus for 15 minutes unless otherwise directed.
DISINTEGRATION TEST FOR TABLETS AND CAPSULES:
This time determines whether tablets or capsules disintegrate within a prescribed time
when placed in a liquid medium under the prescribed experimental conditions.
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For the purpose of this test, disintegration dose not imply complete solution or the
tablet of capsule or even its active constituent. Disintegration 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.
APPRATUS:
a. A rigid basket-rack assemble supporting six cylindrical glass tubes, 77.5+2.5 mm
long, 21.5 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, 90 mm
in diameter and 6 mm thick, perforated by 6 holes having the same diameter as the
tubes. The holes are equidistant from the center of the plate and are equally spaced
from one another. Attached to he under side of the lower plate is a piece of woven
gauze made from stainless steel wire 635 micro I n diameter and having nominal
mesh apertures of 2.00 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 77.5 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 frequency of between 28 and 32 cycles per minute through
a distance of 50 to 60 mm. The design of the basket- rack assembly may be some
what different provided specifications for the glass tubes and the screen mesh size
are unchanged.
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d. A cylindrical disc for each tube, each 20.7 + 0.15 mm in diameter and 9.5 +0.15
mm thick. Made of transparent plastic with a relatively density of 1.18 to 1.20, and
pierced with five holes, each 2 mm diameter, in the center and other four spaced
equally on a circle of radius 6 mm form the center of the disc. Four equally spaced
grooves are cut in lateral surface of the disc in such a way that at the upper surface
of the disc they are 9.5 mm wide and 2.55 mm deep ands at the lower surface 1.6
mm square.
e. The assembly is suspended in the liquid medium in a suitable vessel, preferably a
1000-ml beaker. The volume of liquid is such that the wire mesh at its highest point
is at least 25 mm below the surface of the liquid, and at its lower point is at least 25
mm above the bottom of the beaker.
f. A thermostatic arrangement for heating the liquid and maintaining the temperature
at 37+2 degree.
BRITISH PHARAMACOPEIAL REQUIRMENTS:
APPRATUS:
a. A rigid basket-rack assembly supporting six cylindrical glass tubes 75.0 to 80.0 mm
long, 21.5 mm in internal diameter and with a wall thickness of about 2 mm.
b. A cylindrical disc for each tube, each 20.55 to 20.85 mm in diameter and 9.35 to
9.65 mm thick, made of transparent plastic with a relative density of 1.18 to1.20.
Pierced with five holes, each 2 mm in diameter, one in the center and the four
spaced equally on a circle of radius 6 mm from the center of the disc. Four equally
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spaced grooves are cut the lateral surface of the disc in such way that at the upper
surface of the disc they are 9.5 mm wide and at the lower surface 1.6 mm square.
c. The tubes are held vertically by two superimposed transparent plastic plates 90 mm
in diameter and thick, perforated by six holes. The holes are equidistant from the
center of the plate and are equally spaced from the center of the plate is apiece of
woven gauze made from stainless steel wire 0.635 mm in diameter an having
nominal mesh aperture of 2.00 mm.
d. The plates are held rigidly in position and 77.5 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 50 to 60 mm at a constant frequency of between
28 and 32 cycles per minute.
e. The assembly is suspended in the specified liquid medium in a suitable vessel,
preferably a 1000-ml beaker. The volume of liquid is such that when the assembly
is in the highest position the wire mesh is at least 15 mm below the surface of the
liquid and when the assembly is in the assembly is in lowest the wire mesh is at
least 25mm a the bottom of the beaker and upper open ends of the tubes remain
above the surface of the liquid.
f. A suitable device maintains the temperature of the liquid at 36 to 38 degree.
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Figure II
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METHOD:
Unless 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.
Suspend the assembly in the beaker containing the specified liquid and operate the
apparatus for the specified time. Remove the assembly from the liquid. 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
capsules; not less then16 of the total of 18 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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BRITISH PHARAMACOPEIAL REQUIRMENTS:
LARGE TABLETS AND LARGE CAPSULES:
APPARATUS:
1. A rigid basket-rack assembly supporting three cylindrical glass tubes 75.0 to
80.0 long, 32.5 to 33.5 mm in internal diameter and with a wall thickness of 2.0
to 3.0 mm.
2. A cylindrical discs for each tube, each 31.40 to 31.70 mm in diameter and 16.3
to 16.5 mm in thick, made of transparent plastic with a relative density of 1.18
to 16.5 mm in thick, made of transparent plastic with a relative density of 1.18
to 1.20, pierced with seven holes, each 3.15 mm in diameter, one in the center
and the other six spaced equally on a circle of radius 4.2 mm from the center of
the disc.
3. The tubes are held vertically by two superimposed transparent plastic plates 97
mm in diameter and 9 mm thick, perforated by three holes. The holes are
equidistant from the center of the plate and are equally spaced from one another.
Attached to the under side of the lower plate is a piece of woven gauze made
from stainless steel wire o.60 to 0.64 mm in diameter and having mesh
apertures of 1.18 to 2.2 mm.
4. The plates are held rigidly in position and 77.5 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
53 to 57 mm at a constant frequency of between 29 and 32 cycles per minute.
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5. The assembly is suspended in the specified liquid medium in a suitable vessel,
preferably a 100-ml beaker. The volume of liquid is such that when the
assembly is in position the wire mesh is at least 15 mm below the surface of the
liquid and when the assembly is in the lowest position the wire mesh is at least
25 mm above the bottom of the liquid.
6. A suitable device maintains the temperature of the liquid at 35 to39 degree.
COATED TABLETS:
Comply with the disintegration test for tablets and capsules, Appendix 7.1. Unless
otherwise directed in the individual monograph, use water as the medium and add a
disc to each tube. Operate the apparatus for 30 minutes for film-coated and for 60
minutes for other coated tablets unless otherwise directed in the individual monograph.
For coated tablets other than film-coated tablets, if any of the tablets have not
disintegrated, repeat the test on a further 6 tablets, replacing the water in the vessel with
0.1 m hydrochloric acid. The tablets comply with the test if all 6 tablets have
disintegrated in the acid medium.
ENTERIC COATED TABLETS:
Comply with the disintegration test tablets and capsules. Appendix7.1. If the tablet has
a soluble coating, immerse the basket in the water at room temperature for 5 minutes.
Suspend the assembly in the beaker containing 0.1 m hydrochloric acid and operate
without the disc for 120 minutes, unless otherwise stated in the individual monograph.
Remove the assembly from the liquid. No tablet shows a sign of cracks that would
allow the escape of the contents of disintegration, apart from fragments of coating.
Replace the liquid in the beaker with mixed phosphate buffer ph 6.8, add a disc to each
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tube and operate the apparatus for a further 60 minutes. Remove the assembly from the
liquid. The tablets pass the test if all six have disintegrated.
BRITISH PHARMACOPIEAL REQUIRMENTS:
METHOD:
Introduce one tablet into each tube, suspend the assembly in the beaker containing
0.1M hydrochloric acid and operate without the discs for 120 minutes, unless otherwise
stated in the individual monograph. Remove the assembly from the liquid. No tablet
shows signs of cracks that would allow the escape of the contents or disintegration,
apart from fragments of coating.
Replace the liquid in the beaker with mixed phosphate buffer pH 6.8, add a disc to each
tube an operate the apparatus for a further 60 minutes. Remove the assembly from the
liquid. The tablets pass the test if all six have disintegrated.
DISPERSIBLE AND SOLUBLE TABLETS:
Disintegrate within 3 minutes when examined by the disintegration test for tablets and
capsules, Appendix 7.1, using water at 24 and 26 degree. Unless otherwise stated in the
individual monograph.
EEFERVESCENT TABLETS:
Place one tablet in a 250-ml beaker containing water at 20 to 30 degree; numerous gas
bubbles are evolved. When 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. Repeat the operation on the further
five tablets. The tablets comply with the test if each of the 6 tablets disintegrates in the
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manner prescribed within 5 minutes, unless otherwise stated in the individual
monograph.
Uniformity of Dispersion:
This test is applicable only to dispersible tablets. Place 2 tablets in 100 ml or water and
stir gently until completely dispersed. A smooth dispersion is obtained which passes
through sieve screen with a nominal mesh aperture of 710 micro meters (sieve number
22).
DISSOLUTION TEST FOR TABLETS AND CAPSULES AS PER
BRITISH PHARMACOPIEA:
APPARATUS 3 (FLOW-THROUGH CELL APPARATUS):
1. A reservoir for the dissolution medium.
2. A pump that forces the dissolution medium upwards through the flow-through
cell.
3. A flow trough cell of transparent material mounted vertically with a filter
system preventing escape of un dissolved particles.
4. A water bath that will maintain the dissolution medium at 36.5 to 37.5 degree.
METHOD:
Introduce the stated volume of the dissolution medium, free from dissolved air, into the
vessel of the apparatus. Warm the dissolution medium to between 36.5 to 37.5 degree.
Unless otherwise stated use one tablet or capsule. When the Apparatus 1 is used, place
the tablet or capsule in a dry basket at the beginning of each test. Lower the basket into
position before rotation. When Apparatus 2 is used, allow the tablet or capsule to sink
to the bottom of the vessel prior to rotation of the paddle. A suitable devise such as a
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wire or glass helix is used to keep tablets or capsules that would otherwise float
horizontal at the bottom of the vessel. Care should be taken to ensure that air bubbles
are excluded from the surface of the tablet or capsule. Operate the apparatus
immediately at the speed of rotation specified in the individual monograph. When
Apparatus 3 is used, place glass beads of suitable size, preferably 0.9 to 1.1 mm in
diameter, with one bead of 4.5 to 5.5 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. Assemble the filter head and fix the parts together by
means of a suitable clamping device. Warm the dissolution medium to between 36.5
and 37.5 degree and introduce it through the bottom of the cell using a suitable pump to
obtain a suitable continuous flow at the specified rate (+5%).
Take sample at 45 minutes or at the prescribed intervals or continuously. Withdraw the
sample from a point half-way between the surface of the dissolution medium and the
top of the rotating basket or blade. Not less than 100 mm from the wall of the vessel, or
from the continuously flowing medium of the flow-through cell. Except in the cases of
continuous flow with the paddle or basket method, where the liquid removed is
returned to the dissolution vessel, and single sampling, add a volume of dissolution
medium equal to the volume of sample withdrawn or compensate by calculation. Filter
the samples at 36.5 to 37.5 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 size.
Repeat the complete operation five times. Where 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 70% of the prescribed or stated amount,
unless otherwise specified in the monograph, except that if one fails this requirement a
further six may be tested individually and all must comply. Where 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 70% of the prescribed or stated amount, unless otherwise stated
amount, unless otherwise specified in the monograph. No retesting is permitted. Where
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. Carry out the test as directed in the individual
monograph and make any necessary correction. Correction factors should not be greater
than 25% of the labeled content.
UNITED-STATE PHARMACOPIEAL REQUIRMENTS:
DISINTEGRATION:
This test is provided to determine compliance with the limits on the Disintegration
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. Determine the type of units under test from the labeling and form
observation, and apply the appropriate procedure to 6 or more dosage units.
For the purpose of this test, disintegration does not imply complete solution of the unit
or even of its active constituent. Complete disintegration is defined as that state in
which any residue of the unit. Except 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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APPARATUS:
The apparatus consist of a basket-rack assembly, a 1000-ml, low-from beaker, 138 to
155 mm in height and having an inside diameter of 97 to 110 mm for the immersion
fluid, a thermostatic arrangement for heating the fluid between 35 to 39 degree, and a
device for raising and lowering the basket in the immersion fluid at a constant
frequency rate between 29 to 32 cycles per minute 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 in such that at
the highest point of the upwards 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 from the bottom of vessel on
the downward stroke. The time required for the upward stroke is equal to the time
required 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 horizontal motion or movement of the
axis from the vertical.
BASKET-RACK ASSEMBLY:
The basket-rack assembly consist of six open-ended transparent tubes, each 7.75+ 0.25
cm long and having an inside diameter of 20.7 to23 mm and a wall 1.0 to 2.8 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, with six holes, each 22 to 26 mm in diameter,
equidistant from the centre of the plate and equally spaced from one another. Attached
to the under surface of the lower plate is a woven stainless steal wire cloth, with has a
plain square weave with 1.8 to 2.2 mm mesh aperture and with a wire diameter of 0.63
+ 0.03 mm. The parts of the apparatus are assembled and rigidly held by means of three
bolts passing through the two plastic plates. A suitable means is provided to suspend
the basket-rack assembly from the raising and lowering device using a point on its
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axis. The design of the basket-rack assembly may be varied somewhat provided the
specifications for the glass tubes and the screen mesh size are made.
DISKS:
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 9.5+ 0.15 mm thick
and 20.7 + 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. 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 are centered 6mm from the axis on imaginary line perpendicular
to the axis and parallel to each other. Four identical trapezoidal shaped planes are cut
into the wall of the cylinder, nearly perpendicular to the end of the cylinder. The
trapezoidal shape is symmetrical its parallel sides coincide with the ends of the
cylinder. The trapezoidal 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
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, and its center lies at a depth of 1.8 mm
from the cylinders circumference. The parallel side of the trapezoid on the top of the
cylinder has a length of 9.4 + 0.2 mm, and its center lies at a depth of 2.6 + 0.1 mm
from the cylinder circumference. All 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.
PROCEDURE:
UNCOATED TABLETS:
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Place 1 tablet in each of the six tubes of the basket and operate the apparatus, using
water maintained at 37 + 2 degree as the immersion fluid unless otherwise specified in
the individual monograph. At the end of the time limit specified in the monograph lift
the monograph lift the basket from the fluid and observes the tablets; all of the tablets
have disintegrated completely. If 1 or 2 tablets fail to disintegrate completely, repeat
the test on 12 additional tablets; not less than of the 18 tablets tested disintegrate
completely.
PLAIN-COATED TABLETS:
Apply the test for uncoated tablets, operating the apparatus for the time specified in the
individual monograph.
DELAYED-RELEASE (ENTERIC COATED) TABLETS:
Place 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 5 minutes. Then
operate the apparatus using simulated gastric fluid maintained at 37+2 as the immersion
fluid. After 1 hr of operation in simulated gastric fluid TS, lift the basket from the fluid
and observe the tablets: the tablet show no evidence of disintegration, cracking, or
softening. Operate the apparatus, using simulated intestinal fluid TS maintained,
cracking, or softening. Operate the apparatus, using simulated intestinal fluid TS
maintained at 37+2 as the immersion fluid for the time specified in the monograph. Lift
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 16 of the total 8 tablets tested disintegrate completely.
BUCCAL TABLETS:
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Apply the test for uncoated tablets. After 4 hrs, lift the basket from the fluid, and
observe the tablets; all of the tablets have disintegrated. If 1 or 2 tablets fail to
disintegrate completely, repeat the test on 12 additional tablets: not less than 16 of the
total l8 tablets tested disintegrate completely.
SUB-LINGUAL TABLETS:
Apply the test for uncoated tablets. Observe the tablets within the time limit specified
in the individual monograph: all of the tablets. Observe the tablets have disintegrated. 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 tablets tested disintegrate completely.
HARD GELATIN CAPSULES:
Apply the test for uncoated tablet. Attach a removable wire cloth, with has a pain
square weave with 1.8 to 2.2 mm mesh aperture and with a wire diameter of 0.60 to
0.655 mm, as describe under basket-rack assembly, to the surface of the upper plate of
the basket-rack assembly. Observe 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 16 of the total of 18 capsules tested disintegrate
completely.
SOFT GELATIN CAPSULES:
Proceed as directed under hard gelatin Capsules.
DISSOLUTION:
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This test is provided to determine compliance with the dissolution requirements where
stated in the individual monograph for a tablet or capsule dosage form. Of the types of
apparatus described herein, use some specified in the individual monograph. Where the
tablets states an article is enteric coated, and a dissolution or disintegration test does not
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.
APPARATUS 2:
Use 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 25+2 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. A 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. A 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. Other validated
sinker devices may be used.
APPARATUS SUITABILITY TEST:
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Individual test 1 tablet of the USP Dissolution Calibrator, Disintegration Type and 1
tablet of USP Dissolution calibrator, No 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.
DISSOLUTION MEDIUM:
Use the solvent specified in the individual monograph. If the dissolution medium is a
buffered solution, adjust the solution so that its pH is within 0.05 unit of the pH
specified in the individual monograph.
TIME:
Where a single time specification is given, the test may be concluded in a shorter period
if the requirement 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
+2%.
PROCEDURE FOR CAPSULES, UNCOATED TABLETS, AND
PLAIN COATED TABETS:
Placed the stated volume of the dissolution medium in the vessel of the apparatus
specified in the individual monograph, assembly the apparatus, equilibrate the
Dissolution medium to 37+0.5 degree, and remove the thermometer. Place 1 tablet or 1
capsule in the apparatus, taking care to exclude air bubbles from the surface of the
dosage –from unit, And immediately operate thus apparatus at the rate specified in the
individual monograph. Within the time interval specified, or at each of the times stated,
withdraw a specimen from a zone 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
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wall. [NOTE: Replace the aliquots withdrawn for analysis with equal volume of fresh
dissolution medium at 37 degree or, where it can be shown that replacement of the
medium is not necessary, correct for the volume change in the calculation. Keep the
vessel covered for the duration of the test, and verify the temperature of the mixture
under test at suitable times] perform the analysis as directed in the individual
monograph. Repeat the test with additional dosage form units. If automated equipment
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.
Where capsule shells interfere with the analysis, remove the contents of not less than 6
capsules as completely possible, and dissolve the empty capsule shells in the specified
volume of the dissolution medium. Perform the analysis as directed in the individual
monograph. Make any necessary correction. Correction factor greater than 25% of the
labeled content is unacceptable.
PROCEDURE FOR A POOLED SAMPLE FOR CAPSULES,
UNCOATED TABLETS AND COATED TABLETS
Use this procedure where procedure for a pooled sample is specified in the individual
monograph. Proceed as directed under procedure for capsules, uncoated tablets and
plain coated tablets. Combine equal volumes of the filtered solution of the six or twelve
individual specimen withdrawn, and use the pooled sample as the test solution.
Determine the average amount of the ingredient dissolved in the pooled sample.
INTERPRETATION
Unit sample until unless specified in the individual monograph, the requirements are
format if the quantities of active ingredient dissolved from the units tested conformed
to the accompanying Acceptance table. Continue the testing through the three stages
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unless the results conform at either S1 or S2. The quantity, Q, is the amount of
dissolved active ingredient specified in the individual monograph expressed as the
percentage of the labeled content; the 5 %, 15%, and 25% values in the acceptance
table are percentages of the labeled content so that these values and Q are in the same
terms.
(Acceptance table written above)
POOLED SAMPLE
Unless otherwise specified in the individual monograph, the requirements are met if the
quantities of the active ingredient dissolved from the pooled sample. Continue testing
through the three stages unless the results conform at either S1 or S2. The quantity Q is
the amount of dissolved active ingredient specified in the individual monograph,
expressed as a percentage of the labeled content.
ACCEPTANCE TABLE FOR POOLED SAMPLE
Stage Number Tested Acceptance Criteria
S1 6Average amount dissolved is not
less than Q+ 10%
S2 6Average amount dissolved
(S1+S2) is equal to or greater than Q+5%
S3 12Average amount dissolved
(S1+S2+S3) is equal to greater than Q.
DRUG RELEASE
This test is provided to determine compliance with drug release requirements where
specified in the individual monograph. Use the apparatus specified in the individual
monograph. Replace the aliquots withdrawn for analysis with equal volume of fresh
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dissolution medium at 37˚ or where it can be shown that replacement of the medium is
not necessary, correct the volume change in the calculation. [NOTE: medium
replacement is not necessary for apparatus 4, which is continuous flow system] Keep
the vessel covered for the duration of the test, and verify the temperature of the mixture
under test at suitable times.
EXTENDED RELEASE ARTICLES-GENERAL DRUG RELEASE
STANDARD:
APPARATUS 1 AND APPARATUS 2:
APPARATUS: proceed as directed under dissolution.
APPPARATUS SUITABILITY TEST, DISSOLUTION MEDIUM,
AND PROCEDURE:
Proceed as directed under dissolution.
TIME:
The test time points, generally three are expressed in hours. Specimens are to be
withdrawn within a tolerance of +2% of the stated time.
INTERPRETATION:
Unless otherwise specified in the individual monograph, the requirements are met if the
quantities of the active ingredient dissolved from the units tested conform to acceptance
table 1. Continue testing through the three levels unless the results conform at either L1
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or L2. Limits on the amount of the active ingredient dissolved are expressed in terms of
the percentage of labeled content. The limit embrace each value of Q, the amount
dissolved at each specified fractional dosing interval. Where more than one range is
specified in the individual monograph, the acceptance criteria apply individually to
each range.
ACCEPTANCE TABLE
LEVEL NUMBER TESTED
CRITERIA
L1 6No individual value lies outside each of the staged ranges and no individual value is less than the stated amount at the final test time.
L2 6The average value to\f the 12 units( L1+L2) lies within each of the stated ranges and is not less than the stated amount at the final test time; none is more than 10% of the labeled content below the state test time.
L3 12
The average value of the 24 units (L1+L2+L3) 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 24 units are more than 10 % of the labeled content below the stated amount at the final test time: and none of the units is more than 20% of labeled content outside each of the stated ranges or more than 20% of the labeled content below the stated amount at the final test time.
APPARATUS 3 (RECIPROCATING CYLINDER)
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APPARATUS:
The assembly consist of the set of cylindrical, flat bottomed glass vessel; a set of glass
reciprocating cylinder; stainless steel fittings (type 316 or equivalent) 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
reciprocate the cylinders vertically inside the vessel and, if desired, index the
reciprocating cylinders horizontally to a different row of vessel. The vessels are
partially immersed in a suitable water bath of any convenient size that permits the
holding the temperature at 37±0.5˚c 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.
A device is used that allows the reciprocation rate to d\be selected and maintained at
the dip rate specified in the individual monograph, within ±5%. An 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.
APPARATUS SUITABILITY TEST:
Individual test 1 tablet of the USP release calibrator tablets (single unit) and a specified
amount content of the USP drug release calibrator beads (multiple unit) 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.
DISSOLUTION MEDIUM:
Proceed as directed under dissolution.
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PROCEDURE:
Place the stated volume of the dissolution medium in vessel of the apparatus, assemble
the apparatus, equilibrate the dissolution medium to 37±5˚c and remove the
thermometer. Place dosage form unit in each of the 6 reciprocating cylinders, taking to
exclude air bubble from the surface of each dosage form unit, immediately operate the
apparatus as specified in the individual monograph. During the upward and down word
stroke, the reciprocating cylinder moves through a total distance of 9.9 to 10.1 cm.
within time interval specified, or at each time stated, raise the reciprocating cylinder
and withdraw a portion of the solution under form a zone midway between the surface
of the dissolution medium and the bottom of each vessel. Perform the analysis as direct
under individual monograph. If necessary repeat the test with additional dosage form
units.
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APPARATUS 4 (FLOW THROUGH CELL):
APPARATUS:
The assembly consists of a reservoir and a pump for dissolution medium: a flow
through cell; a water bath that maintain dissolution medium at 37±0.5˚c. 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 240 and 960 ml per hour, with standard flow rates of 4, 8,
and 16 ml per minute. It must be volumetric to deliver constant flow independent of
flow resistance in the filter device; the flow profile is sinusoidal with a pulsation of
120±10 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 cell; standard
cell diameter are 12 and 22.6 mm; the bottom cone is usually filled with small glass
beads of about 1 mm diameter with 1 bead of about 5 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 37±0.5˚c.
The apparatus uses a clamp mechanism and two O-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.
Use polite tubing with a 1.6 mm inner diameter and chemically inert flanged end
connections.
APPARATUS SUITABILITY TEST AND DISSOLUTION
MEDIUM:
Proceed as directed under dissolution.
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PROCEDURE:
Place the glass beads into the cell specified in the monograph. Place 1 dosage form unit
on the top of the beads or if specified in the monograph on a wire carrier. Assemble the
filter helix and fix the part together by means of suitable clamping device. Introduce by
the pump dissolution medium warmed to 37±5˚ through the bottom of the cell to obtain
the flow rate specified in the individual monograph and measured with accuracy.
Collect the elute by fractions at each of the time stated. Perform the analysis as directed
in the individual monograph.
Where capsule shells interfere with the analysis, remove the contents of not less than 6
capsules as completely as possible, and dissolve the empty capsule shells in the
specified volume of dissolution medium.
TIME AND INTERPRETATION:
Proceed as directed under apparatus 1 and 2.
DELAYED-RELEASE (ENTERIC COATED) ARTICLES-
GENERAL DRUG RELEASE STANDARD:
Use Method A or Method B and the apparatus specified in the individual monograph.
Conduct the apparatus suitability test as directed under dissolution. All test ties stated
are to be observed within a tolerance of ±2%, unless otherwise specified.
METHOD A:
PROCEDURE: (Unless otherwise directed in the individual
monograph)
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ACID STAGE:
Place 750 ml of 0.1N HCl in the vessel, and assemble the apparatus. Allow the medium
to equilibrate to a temperature of 37±0.5˚c. Place 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.
After 2 hours of the operation in 0.1N HCl, withdraw an aliquot of the fluid and
proceed immediately as directed for the buffer stage.
Perform the analysis of the aliquot using the procedure specified in the test for drug
release in the individual monograph.
Unless otherwise specified in the individual monograph, the requirements of this
portion of the test are met if the quantities, based on the % labeled content, of active
ingredient dissolved from the units tested conform to acceptance table 2. Continue
testing through all levels unless the results of both acid and buffer stages conform at an
earlier level.
ACCEPTANCE TABLE 2:
LEVEL NUMBER TESTED CRITERIA
A1 6 No individual value exceeds 10% dissolved
A2 6Average of the 12 units (A1+A2) is not more than 10% dissolved, and no individual unit is greater than 25% dissolved.
A3 12Average of the 24 units (A1+A2+A3) is not more than 10% dissolved, and no individual unit is greater than 25% dissolved.
BUFFER STAGE:
With the apparatus operating at the rate specified in the monograph, add to the fluid in
the vessel 250 ml of 0.20M tri basic sodium phosphate that has been equilibrated to
37±0.5˚c. Adjust if necessary with 2 N sodium hydroxide to a pH of 6.8±0.05.
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Continue to operate the apparatus for 45 minutes, or for the time specified in the
individual monograph. At the end of the time period, withdraw an aliquot of the fluid.
And perform the analysis using 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 requirement for minimum amount is dissolved is
met an earlier time.
INTERPRETATION:
Unless otherwise specified in the individual monograph, the requirements are met if the
quantities of the active ingredient from the units tested conform to acceptance table 3.
Continue testing through the three levels the results of both stages conform at an earlier
level. The value of Q in acceptance table 3 is 75% dissolved unless otherwise specified
in the individual monograph. The quantity, Q, specified in the individual monograph, is
the total amount of active ingredient dissolved in both the buffer stages, expressed as a
percentage of the labeled content so that these values and Q are in the same terms.
ACCEPTANCE TABLE 3:
LEVEL NUMBER TESTED CRITERIA
B1 6 Each unit is not less than Q±5%
B2 6Average of 12 units (B1+B2) is equal to or greater than Q, and no unit is less than Q-15%
B3 12Average of 24 units (B1+B2+B3) is equal to or greater than Q, not more than two units are less than Q-15% and no unit is less than Q-25%
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METHOD B:
PROCEDURE: (unless otherwise directed in the individual
monograph)
ACID STAGE:
Place 1000 ml of 0.1 N HCl in the vessel, and assemble the apparatus. Allow the
medium to equilibrate to a temperature of 37±0.5 ˚c. Place 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. After 2 hours of operation in 0.1 N HCl, withdraw an aliquot of the
fluid, and proceed immediately as directed under buffer stage.
Perform an analysis of the aliquot using the procedure specified in the test for drug
release in the individual monograph.
Unless otherwise specified in the individual monograph, the requirement of this portion
of the test are met if the quantities, based on the % of the labeled content of active
ingredient dissolved from the units tested conform to acceptance table 2 under method
A. continue testing through all levels unless the results of both acid and stage conform
at an earlier level.
BUFFER STAGE:
NOTE: for this stage procedure, use buffer that previously has been equilibrated to a
temperature of 37±0.5 ˚c.
Drain the acid from the vessel and add to the vessel 1000 ml of pH 6.8 phosphate
buffer, prepared by mixing 0.1 N HCl with 0.20 M tribasic sodium phosphate (3:1) and
adjusting, if necessary, with 2 N HCl or 2 N NaOH to a pH of 6.8±0.05. Continue to
operate the apparatus for 45 minutes or for the time specified in the individual
monograph. At the end of the time period, withdraw an aliquot of the fluid, and perform
the analysis using the procedure specified in the test for drug release in the individual
monograph. The test may be concluded in the shorter period than that specified for the
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buffer stage if the requirement for the minimum amount is dissolved met an earlier
time.
INTERPRETATION:
Proceed as directed for interpretation under method A.
TRANSDERMAL DELIVERY SYESTEM- GENERAL DRUG
RELEASE STANDARDS:
APPARATUS 5 (PADDLE OVER DISC)
APPARATUS:
Use 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 37±0.5˚c. A distance of 25±2 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 minimize the evaporation. The disk assembly for holding the
transferal system is designed to minimize 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.
APPARATUS SUITABITY TEST AND DISSOLUTION MEDIUM:
Proceed as directed for apparatus 2 under dissolution.
PROCEDURE:
Place the stated volume of the dissolution medium in the vessel, assemble the apparatus
without disk assembly, and equilibrate the medium to 37±0.5 ˚c. apply the transdermal
system to three disk assembly, assuring that the release surface of the system is as flat
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as possible. The system is attached to the disk by applying a suitable adhesive to the
disk assembly. Dry for 1 minute. Press the system release the surface side up, onto the
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. Place the disk assembly flat at the bottom of the vessel with release surface
facing up and to the parallel edge of the paddle is 25±2 mm from the surface of the
dissolution medium. The bottom edge of the paddle is 25±2 mm from the surface of the
disk assembly. Immediately operate the apparatus at the rate specified in the
monograph. At each sampling time interval, withdraw a specimen from a zone midway
between the surface of the dissolution medium and the top of the blade, not less than 1
cm from the vessel wall. Perform the analysis on each sample aliquots as directed in the
individual monograph, correcting for any volume losses, are necessary. Repeat the test
with additional transferal systems.
TIME:
The test point generally three, is expressed in hours. Specimens are to be withdrawn
within a tolerance of +15 minutes or +2 % of the stated time, the tolerance that results
in the narrowest time interval being selected.
INTERPRETATION:
Unless otherwise specified in the individual monograph, the requirements are met if the
quantities of the active ingredients released from the system conform to the Acceptance
table 4 for transferal drug delivery system. Continue testing through the three levels
unless the results conform at either L1 or L2.
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ACCEPTANCE TABLE 4:
LEVEL NUMBER TESTED CRITERIA
L1 6No individual value lies outside the stated range.
L2 6
The average values of 12 units (L1+L2) lie within the stated range. No individual value is outside the stated range by more than 10% of the average of the stated range.
L312
The average value of the 24 units (L1+L2+L3) lies within the stated range. No of the 2 of the 24 units are outside the stated range by more than 10 % of the stated range and none of the units is outside the stated range by more than 20% of the average of the stated range.
APPARATUS 6 (CYLINDER):
APPARATUS:
Use 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 32±0.5 ˚c 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 25±2 mm during the test.
DISSOLUTION MEDIUM:
Use the medium specified in the individual monograph.
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PROCEDURE:
Place the stated volume of the dissolution medium in the vessel of the apparatus
specified in the individual monograph, assemble the apparatus and equilibrate the
dissolution medium to 0.5 ˚c. Unless otherwise directed in the individual monograph
prepares the test system prior to test as follows. Remove the protective liquor 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. Place 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. Press the cylinder in the apparatus and immediately rotate at the rate specified
in the individual monograph. Within the interval specified or each of the times stated,
withdraw a quantity of dissolution medium for analysis of a top of the rotating cylinder,
not less than 1 cm from the vessel wall. Perform the analysis as directed in the
individual monograph, correcting for any volume losses as necessary. Repeat the test
with transferal drug delivery system.
TIME:
Proceed as directed under apparatus 3.
INTERPRETATION:
Unless otherwise specified in the individual monograph, the requirements are met if the
quantities of active ingredient released from the system conform to acceptance table 4
for transferal drug delivery system. Continue the testing through the three levels unless
the results conform at either L1 or L2.
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APPARATUS 7 (RECIPROCATING CYLINDER)
NOTE: This apparatus may also be specified for use with a variety of dosage
forms.
APPARATUS:
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 horizontally 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 size that permits
maintaining the temperature T, inside the containers at 37±0.5˚c or within the allowable
range. As specified in the individual monograph during the test. No 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.
DISSOLUTION MEDIUM:
Use the dissolution medium specified in the individual monograph.
PROCEDURE:
Suspend 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 equilibrated container pre-equilibrated to temperature, T. reciprocate
at a frequency of 30 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. Remove the solution containers from the bath, cool to room temperature and
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add sufficient solution to correct the evaporative loss. Perform the analysis as directed
in the individual monograph. Repeat the test with additional drug delivery system as
required in the individual monograph.
INTERPRETATION:
Unless otherwise specified in the individual monograph, the requirements are met if the
quantities of active ingredient released from the system conform to acceptance table 4
for coated tablet drug delivery system. Continue the testing through the three levels
unless the results conform at either L1 or L2.
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_________________________________________________________ References
1. The science and practice of pharmacy 20th edition.
2. Pharmaceutical dosages form–tablets volume 2,2nd edition by H.A. Lieberman and
L-Lechman
3. Pharmaceutical dosage form-capsules, volumes 2,2nd edition by H.A. Lieberman
and L-Libra am
4. Dispensing pharmacy by G.K. Janis
5. Pharmaceutics the science of dosage form design by M.E. AULTON.
6. Encyclopedia of pharmaceutical technology 2nd edition volume 3
7. Comprehensive pharmacy review 5th Edition by loen shargel.
8. Theory and practice of industrial pharmacy, 3rd edition by Leon Lechman.
9. Copper and gin’s dispensing for pharmaceutical student 12th Edition by S.J.Carter.
10. Pharmaceutical dosage form and drug delivery system, 7th edition by Howard
C. Anseal.
11. British pharmacopeias -2001, volume 1 and volume 2
12. United state pharmacopeias national formulary 2003 , Asian edition
13. Indian pharmacopeias 1996
14. Oral drug absorption prediction and asseement by Jennifer B.Dressman.
15. Drug and pharmaceutical science, 2nd Edition, volume 67 by G Welling francs
L.S.Tse.
16. Oral drugs absorption drugs and pharmaceutical science by dress mar.
17. Davies b and monist physiological parameter in laboratory animal and human.
18. Pharmacopeias and formularies by Harkishan Singh.
19. Pharmaceutical dosage form and drug delivery system 8th Edition by Loyd V. Allen
and J.R., Nicholas.
20. Handbook of safe drug usage delivery by V.R. Shenoy and A.R. Shenoy.
21. Tutorial book of pharmaceutics by J.Bently.
22. Modern dispensing by guad.
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INDEX
SR. NO. CONTENT PAGE. NO.
1 Introduction
2 Classification
3 Monograph
4 Standards
5 Apparatus
6 References
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