Oral Solid Dosage Forms

_________________________________________________________ _ 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.

/tt/file_convert/55cf966e550346d0338b6e08/document.doc 1

_________________________________________________________ _ 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.


_________________________________________________________ _ 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.


_________________________________________________________ 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


_________________________________________________________ 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.


_________________________________________________________ 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.


_________________________________________________________ References

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.


_________________________________________________________ References

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


_________________________________________________________ References

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 .


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.


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.


PRODUCTION:

A suitable test is carried out to demonstrate the appropriate release of the active

ingredients.


_________________________________________________________ References


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.


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.


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,


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.


_________________________________________________________ References

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).


_________________________________________________________ References

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


_________________________________________________________ References

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:


_________________________________________________________ References

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.


_________________________________________________________ References

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.


_________________________________________________________ References

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.


_________________________________________________________ References


_________________________________________________________ References

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.


_________________________________________________________ References

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%.


_________________________________________________________ References

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.


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:


_________________________________________________________ References

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


_________________________________________________________ References

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.


_________________________________________________________ References

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.


_________________________________________________________ References

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


_________________________________________________________ References

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.


_________________________________________________________ References

Figure II


_________________________________________________________ References


_________________________________________________________ References

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.


_________________________________________________________ References

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.


_________________________________________________________ References

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


_________________________________________________________ References

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


_________________________________________________________ References

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


_________________________________________________________ References

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,


_________________________________________________________ References

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.


_________________________________________________________ References

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


_________________________________________________________ References

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:


_________________________________________________________ References

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:


_________________________________________________________ References

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:


_________________________________________________________ References

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:


_________________________________________________________ References

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


_________________________________________________________ References

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


_________________________________________________________ References

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


_________________________________________________________ References

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:


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


_________________________________________________________ References

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)


_________________________________________________________ References

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:



_________________________________________________________ References

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.


_________________________________________________________ References


_________________________________________________________ References

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:



_________________________________________________________ References

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)


_________________________________________________________ References

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.


_________________________________________________________ References

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:


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:


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%


_________________________________________________________ References

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


_________________________________________________________ References

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


_________________________________________________________ References

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:


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.


_________________________________________________________ References

ACCEPTANCE TABLE 4:


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.


_________________________________________________________ References

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:


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.


_________________________________________________________ References

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


_________________________________________________________ References

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:


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.


_________________________________________________________ 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.


_________________________________________________________ References

INDEX

SR. NO. CONTENT PAGE. NO.

1 Introduction

2 Classification

3 Monograph

4 Standards

5 Apparatus

6 References


Oral Solid Dosage Forms

Documents

Transcript of Oral Solid Dosage Forms