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.
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.
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.
<b>Disadvantages of Tablets:</b>
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.
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.
CLASSIFICATION OF SOLID DOSAGE FORM
1) 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:
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.
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.
INDIAN PHARMACIA REQUIREMENTS:
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.
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 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.
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.
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).
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
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:
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.
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.
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.
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.
DISSOLUTION MEDIUM:
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%.
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:
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 ACCEPTANCE
CRITERIA
S1 6 Each unit is not less than
D*+5%
S2 6 Average 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.
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.
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 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.
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.
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.
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 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 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 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, 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.
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 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:
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:
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:
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:
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 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 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
6 Average amount dissolved is not less than Q+ 10%
S2
6 Average amount dissolved (S1+S2) is equal to or
greater than Q+5%
S3
12 Average 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 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 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
6 No 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
6 The 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)
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.
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.
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.
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)
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 6 Average of the 12 units (A1+A2) is not more than 10% dissolved, and no individual unit is greater than 25% dissolved.
A3 12 Average 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. 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 6 Average of 12 units (B1+B2) is equal to or greater than Q, and no unit is less than Q-15%
B3 12 Average 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%
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 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 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.
ACCEPTANCE TABLE 4:
LEVEL NUMBER TESTED CRITERIA
L1 6 No 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.
L3
12
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.
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.
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 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.
References:
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Libraam
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13. Indian pharmacopeias 1996
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