Quality Control of Tablets (Evaluation Tests)

The quantitative evaluation and assessment of a tablets chemical, physical and bioavailability properties are important in
the design of tablets and to monitor product quality. These properties are important since chemical breakdown or
interactions between tablet components may alter the physical tablet properties, and greatly affect the bioavailability of
the tablet system. There are various standards that have been set in the various pharmacopoeias regarding the quality of
pharmaceutical tablets. These include the diameter, size, shape, thickness, weight, hardness, disintegration and dissolution
characters. The diameters and shape depends on the die and punches selected for the compression of tablets. The
remaining specifications assure that tablets do not vary from one production lot to another. The following standards or
quality control tests should be carried out on compressed
General Appearance:
It is the visual identity and overall elegance which is essential for consumer acceptance. This includes: Size, shape,
and thickness: this is important to facilitate packaging and to decide which tablet compressing machine to use.
Organoleptic properties: which include color and odor of the tablets. Tablet color is important because it affects rapid
identification of the medication, and odor is important to identify any stability problems. An example is Aspirin which
gives the odor of acetic acid if any stability problem occurred.
1. Official and unofficial tests.
Official Tests: Weight variation, disintegration, dissolution, drug content.

Non-Official Tests: hardness, friability, Tensile strength, Brittle fracture index (BFI)

I- Non official tests:

(1) Hardness (crushing strength): It is the load required to crush the tablet when placed on its edge. The resistance of
tablets to capping, abrasion or breakage under conditions of storage, transportation and handling before usage depends on
its hardness. The small and portable hardness tester was manufactured and introduced by Monsanto in the Mid 1930s. It
is now designated as either the Monsanto or Stokes hardness tester. The instrument measures the force required to break
the tablet when the force generated by a coil spring is applied diametrally to the tablet. The Strong-Cobb Pfizer and
Schleuniger apparatus which were later introduced measures the diametrically applied force required to break the tablet.
Hardness, which is now more appropriately called crushing strength determinations are made during tablet production and
are used to determine the need for pressure adjustment on tablet machine. If the tablet is too hard, it may not disintegrate
in the required period of time to meet the dissolution specifications; if it is too soft, it may not be able to withstand the
handling during subsequent processing such as coating or packaging and shipping operations.
Why do we measure hardness?

Hardness determinations are made throughout the tablet runs to determine the need for pressure adjustments on the
tableting machine.
Hardness can affect the disintegration. So if the tablet is too hard, it may not disintegrate in the required period of
time. And if the tablet is too soft, it will not withstand the handling during subsequent processing such as coating or
packaging.

In general, if the tablet hardness is too high, we first check its disintegration before rejecting the patch. And if the
disintegration is within limit, we accept the patch.
If Hardness is high + disintegration is within time accept the patch.
Factors Affecting the Hardness:
1. Compression of the tablet and compressive force.
2. Amount of binder. (More binder more hardness)
3. Method of granulation in preparing the tablet (Wet granulation method gives highest hardness)

4. Characteristics of the drug.

Limits: 4 kilograms minimum and 8 kilograms maximum. The force required to break the tablet is measured in kilograms
and a crushing strength of 4Kg is usually considered to be the minimum for satisfactory tablets. Oral tablets normally
have a hardness of 4 to 10kg; however, hypodermic and chewable tablets are usually much softer (3 kg) and some
sustained release tablets are much harder (10-20 kg).Tablet hardness have been associated with other tablet properties
such as density and porosity. Hardness generally increase with normal storage of tablets and depends on the shape,
chemical properties, binding agent and pressure applied during compression.
Make hardness test on 5 tablets and then take the average hardness
(2) Friability: Friction and shock are the forces that most often cause tablets to chip, cap or break. The friability test is
closely related to tablet hardness and is designed to evaluate the ability of the tablet to withstand abrasion in packaging,
handling and shipping. It is usually measured by the use of the Roche friabilator. A number of tablets are weighed and
placed in the apparatus where they are exposed to rolling and repeated shocks as they fall 6 inches in each turn within the
apparatus. After four minutes of this treatment or 100 revolutions, the tablets are weighed and the weight compared with
the initial weight. The loss due to abrasion is a measure of the tablet friability. The value is expressed as a percentage. A
maximum weight loss of not more than 1% of the weight of the tablets being tested during the friability test is considered
generally acceptable and any broken or smashed tablets are not picked up. Normally, when capping occurs, friability
values are not calculated. A thick tablet may have less tendency to cap whereas thin tablets of large diameter often show
extensive capping, thus indicating that tablets with greater thickness have reduced internal stress.
It is the tendency of tablets to powder, chip, or fragment and this can affect the elegance appearance, consumer
acceptance of the tablet, and also add to tablets weight variation or content uniformity problems.
Friability is a property that is related to the hardness of the tablet.
An instrument called Friabilator is used to evaluate the ability of the tablet to withstand abrasion in packaging,
handling, and shipping.
Roche Friabilator: Subjects a number of tablets to abrasion and shock by utilizing a plastic chamber that revolves at 25
rpm, dropping the tablets a distance of 6 inches with each revolution. After a given number of rotations the tablets are
weighed and the loss in weight indicates the ability of the tablets to withstand this type of wear.
Procedure:
1. Weigh 20 tab altogether = W1
2. Put these tablets in the friabilator and adjust the instrument at 100 rpm (i.e. = 25 rpm for 4 min)
3. Weigh the 20 tablets (only the intact ones) = W2
( w1 w2)
* 100
4. Friability (% loss) =
w1
RESULTS: It must be 1% but if more we do not reject the tablets as this test is non-official.
(3) Tensile strength
A non-compendial method of measuring the mechanical strength of tablets that is now widely used is the tensile strength.
This is the force required to break a tablet in a diametral compression test. The radial tensile strength, T, of the tablets can
be calculated from the equation:
T=2F/dH
where F is the load needed to break the tablet, and d and H are the diameter and thickness respectively. Several
precautions must be taken when using the equation. Various factors e.g. test conditions, deformation properties of the
material, adhesion conditions between compact and its support and tablet shape may influence the measurements of the
tensile strength .
Some authors have suggested the determination of axial tensile strength because of the sensitivity of the radial tensile
strength measurements to crack propagation variations. The axial tensile strength (Tx) can be calculated from the
following relationship:

Tx = 4 F / d2
Tensile strength has been used in combination with indentation hardness to evaluate tabletting performance of materials.
The indentation hardness is a time-dependent property used to measure the plastic yield of a material. It can be determined
by either static methods (e.g. the Brinell, Vickers and Rockwell hardness tests) or the dynamic methods. The static
indentation methods involve the formation of a permanent indentation on the surface of the material tested and the
hardness is determined by means of the load applied and the size of the indentation formed. In the dynamic indentation
tests, either a pendulum is allowed to strike from a known distance or an indenter is allowed to fall under gravity unto the
surface of the test material. The hardness is then determined from the rebound height of the pendulum or the volume of
the resulting indentation. Using an apparatus consisting of a steel sphere pendulum acting as an indenter, Hiestand et al.
estimated the hardness (i. e. the mean deformation pressure) of compacted materials by dividing the energy consumed
during the impact by the volume of indentation.
(4) Brittle fracture index (BFI)
Hiestand et al. have studied the effects of decompression on the tabletting performance of pharmaceutical materials and
stated that whether or not fracture occurs during the shear deformation which accompanies decompression depends on the
ability of the materials to relieve stresses by plastic deformation without undergoing brittle fracture and this ability is a
time-dependent phenomenon. Those materials that relieve stress rapidly are less likely to cap or laminate. The brittleness
test is based on the Griffith fracture theory which teaches that, for crack growth to occur, the energy stored at the tip of a
crack must just exceed the energy required to form two new surfaces resulting from the propagation of the crack. Also, the
amount of energy stored at the tip of a crack is a function of the dimensions of the crack.
In the light of this theory, Hiestand et al. showed that when compacts are made with a small axially-oriented round hole at
their centre, the compact is nearly always weakened. Under the conditions of the tensile strength test, elasticity theory
predicts that the stress concentration factor for the hole should be about 3.0. Hiestand18 showed that for isotropic
materials, the ratio of compressive stress at the centre of a compact to the tensile stress, which causes fracture, has a value
of 3.7. However, recent studies have shown that for a ratio of hole diameter to disc of about 0.1, the stress concentration
factor, i.e. the ratio between tensile stress at the inner boundary of the hole and the tensile stress of a tablet having no hole,
should be around 1019,20. Thus, the BFI is obtained by comparing the tensile strength of tablets with a hole at their
centre, which acts as a built-in stress concentration defect, with the tensile strength of tablets without a hole, both at the
same relative density18,21. The brittle fracture index (BFI) of the tablets was calculated using the following equation
BFI = [(T / To) 1 ]
Where T is the tensile strength of the tablet without a hole and To, to the tensile strength of a tablet with a hole. The
theoretical value of BFI range is 0 - 1 when the stress concentration factor is 3. Since the BFI is an inverse measure of
localized stress relief, it should indicate the tendency of a tablet to laminate or cap. In principle, BFI values in excess of
unity may occur. In practice, however, one probably cannot make an intact tablet of a material with a BFI of 1. Therefore,
the observed range of values may not exceed the 0 - 1 range. Where by the closer the value of BFI to 0, the less stress
relief takes place. A high value of BFI is an indication of the tendency of the tablet to laminate during the compaction
process. A low BFI value is desirable for minimal lamination and capping during production.
Robert and Rowe extended the determination of the BFI to compact of tablet-sized dimensions. This allows the BFI to
be measured at strain rates and conditions approaching those normally used in tabletting. They found the BFI values for
microcrystalline cellulose, tablettose and heavy magnesium carbonate to be in good agreement with the results of previous
workers. Itiola & Pilpel using both granular and powdered metronidazole formulations studied the mechanical properties
of the tablets and differentiated between the bond strength of the tablets as measured by their tensile strength and the
tendency of the tablets to laminate or cap as measured by the brittle fracture index values. They found that tablets made
from granules had lower tensile strength than those made from powders but were also less brittle.
The BFI have also been used to characterize the mechanical properties of pharmaceutical formulations9, and some local
starches, namely cassava, potato and yam starches. Tablets of these starches were shown to possess low tensile strength
values, but also had low BFI values. Studies have also shown that the BFI is affected by the nature and concentration of
binding agent, compression pressure and compression speed. Generally, the higher the BFI values, the more friable a
tablet is likely to be.
II- Official Tests:

(1) Disintegration: It is the time required for the tablet to break into particles, the disintegration test is a measure only of
the time required under a given set of conditions for a group of tablets to disintegrate into particles. In the present
disintegration test the particles are those that will pass through a 10-mesh screen. Complete disintegration occurs when no
residue of the tablet still present on the screen except the insoluble ingredients as the shell or the coat of the tablet.
Disintegration device (STANDARD: INDIAN PHARMACOPOEA):
a. A rigid basket-rack assembly 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 (see Fig).
b. The tubes are held vertically by two superimposed transparent plastic plates, 90mm in diameter and 6mm thick
perforated by six holes having the same diameter as the tubes. The holes are equidistant from the centre 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 635 m m in diameter and having nominal mesh apertures of 2.00 mm. The
upper plate is covered with a stainless steel disc perforated by six holes, each about 22 mm in diameter, which fits
over the tubes and holds them between the plastic plates. The holes coincide with those of the upper plastic plate
and the 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 centre 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 somewhat 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 thick in diameter and 9.5 0.15 mm thick, made of
transparent plastic with a relative density of 1.18 to 1.20, and pierced with five holes, each 2 mm in diameter, one
in the centre and the other four spaced equally on a circle of radius 6mm from the centre of the disc. Four equallyspaced grooves are cut in the Lateral surface of the disc in such a way that at the upper surface of the disc they are
9.5mm wide and 2.55mm deep and 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 25mm below the surface of the liquid, and at its
lower point is at least 25mm above the bottom of the beaker.
f.

A thermostatic arrangement for heating the liquid and maintaining the temperature at 37 2 .

Liquids used in disintegration:

Water, simulated gastric fluid (PH = 1.2 Hcl), or Simulated intestinal fluid (PH = 7.5, KH 2PO4 (phosphate buffer) +
pencreatin enzyme +NaoH)
Limits:

Uncoated tablets:
According to U.S.P
According to B.P.
According to I.P.

Medium
Simulated gastric fluid
Water
Water

Temperature
37oC
37oC
37oC

Time limit
Not exceed 30
Not exceed 15
Not exceed 15 (unless otherwise directed.)

U.S.P:
1. Start the disintegration test on 6 tablets.
2. If one or two tablets from the 6 tablets fail disintegrate completely
another 12 tablet. (i.e. the whole test will consume 18 tablets).
3. Not less than 16 tablets disintegrate completely within the time. If
disintegrate, the batch must be rejected.
I.P:
1. Start the disintegration test on 6 tablets.
2. If one or two tablets from the 6 tablets fail disintegrate completely
another 12 tablet. (i.e. the whole test will consume 18 tablets).
3. Not less than 16 tablets disintegrate completely within the time. If
disintegrate, the batch must be rejected.

within 30 minutes repeat the same test on

more than two tablets (from the 18) fail to

within 15 minutes repeat the same test on

more than two tablets (from the 18) fail to

Coated tablets (I.P.): use water as the medium and add a disc to each tube. Operate the apparatus for 30 minutes for
film-coated tablets 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 0.1M hydrochloric acid. The tablets comply with the test if all 6 tablets have
disintegrated in the acid medium.
Enteric-coated Tablets (I.P.): If the tablet has a soluble external coating, immerse the basket in water at room
temperature for 5 minutes. 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 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.
Dispersible and Soluble Tablets (I.P.): Disintegrate within 3 minutes when examined by the disintegration test for
tablets and capsules, using water at 24o to 26o, unless otherwise stated in the individual monograph.
Effervescent Tablets: Place one tablet in a 250-ml beaker containing water at 20o to 30o; numerous gas bubbles are
evolved. When the evolution of gas around the tablet or its fragments has ceased the tablet shall have disintegrated, being
either dissolved or dispersed in the water so that no agglomerates of particles remain. Repeat the operation on a further 5
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 of water and stir
gently until completely dispersed. A smooth dispersion is obtained which passes through a sieve screen with a nominal
mesh aperture of 710 m m (sieve number 22).
Theories of disintegration
Several mechanisms of tablet disintegration have been proposed. Some of these are given below. Even though these
concepts are listed separately, inter-relationships probably occur in almost all tablet formulations.
Evolution of gas: If a gas is evolved by a chemical reaction when the tablet comes into contact with water, then the tablet
will disintegrate. This is the basis for the manufacture of effervescent tablets. An example of such a reaction is of sodium
bicarbonate with citric and tartaric acids, which yields carbon dioxide. Peroxides incorporated in certain formulations
decompose in the presence of oxygen and this also causes disintegration.

Heat of wetting: The heat produced when a tablet is immersed in water causes the entrapped air in the tablet to expand
and exert sufficient pressure to disintegrate the tablet.
Effect of water absorption: The water absorbed by the tablet initiate disintegration, but this depends on the solubility of
the drug and other ingredients present.
Swelling: The grains of the disintegrant, particularly of starches, swell in the presence of water and exert pressure on the
granules to force them apart. Shangraw et al reported that tablets of water insoluble drugs disintegrated faster with starches
than those of water soluble drugs due to the diminished water absorption capacity of the starches in the latter case.
Porosity of tablets: It has been shown that penetration of water into a tablet is proportional to its mean pore diameter or
porosity. The porosity and permeability of tablets decrease as the tabletting pressure is increased, and as the porosity
decreases, the disintegration time increases. Though no quantitative relationships have been reported between
disintegration and penetration times, generally short disintegration times are associated with rapid fluid penetration.
(2) Dissolution: Dissolution is the process by which a solid solute enters a solution. In the pharmaceutical industry, it may
be defined as the amount of drug substance that goes into solution per unit time under standardized conditions of
liquid/solid interface, temperature and solvent composition.
Dissolution is considered one of the most important quality control tests performed on pharmaceutical dosage forms and is
now developing into a tool for predicting bioavailability, and in some cases, replacing clinical studies to determine
bioequivalence. Dissolution behaviour of drugs has a significant effect on their pharmacological activity. In fact, a direct
relationship between in vitro dissolution rate of many drugs and their bioavailability has been demonstrated and is
generally referred to as in vitro-in vivo correlation.Solid dosage forms may or may not disintegrate when they interact
with gastrointestinal fluid following oral administration depending on their design

Schematic diagram of the dissolution process

Apparatus (I.P. STANDARD): Two types of apparatuses are used
Apparatus 1(Paddle apparatus):

a. A cylindrical vessel, A, made of borosilicate glass or any other suitable transparent material, with a hemispherical
bottom and with a nominal capacity of 1000ml (see Fig.). The vessel has a flanged upper rim and is fitted with a
lid that has a number of openings, one of which is central.

b. A motor with a speed regulator capable of maintaining the speed of rotation of the paddle within 4% of that
specified in the individual monograph. The motor is fitted with a stirring element which consists of a drive shaft
and blade forming a paddle, B (see Fig)
The blade passes through 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 axis is within 2 mm of the axis of the vessels 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. Water -bath set to maintain the dissolution medium at 36.5 to 37.5. The bath liquid is kept in constant and
smooth motion during the test. 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 minimised.
Apparatus 2 (Basket apparatus):

The assembly is the same as in Apparatus 1 except that in the stirring element the paddle is replaced by a basket, D (see
Fig.). The metallic shaft rotates smoothly and without significant wobble. The basket consists of two components. 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 introduction of the preparation being examined and that firmly hold the lower part of the basket
concentric with the axis of the vessel during rotation. The lower detachable part of the basket is made of welded-steam
cloth, with a wire thickness of 0.254 mm diameter and with 0.381mm square openings, formed into a cylinder with
narrow rim of sheet metal around the top and the bottom. The basket may be plated with a 2.5m m layer of gold for use
with acidic media. The distance between the inside bottom of the vessel and the basket is maintained at 23 to 27mm
during the test.
Dissolution medium: Use the dissolution medium specified in the individual monograph. If the medium is a buffered
solution, adjust the solution so that its pH is within 0.05 units of the pH specified in the monograph. The dissolution
medium should be de-aerated 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, specimen 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. Unless otherwise stated use one tablet or capsule.

When Apparatus 1 is used, allow the tablet or capsule to sink to the bottom of the vessel prior to the rotation of the paddle.
A suitable device such as a wire of glass helix may be used to keep horizontal at the bottom of the vessel tablets or
capsules that would otherwise float. Care should be taken to ensure that air bubbles are excluded from the surface of the
tablet or capsule. When Apparatus 2 is used, place the tablet or capsule in a dry basket at the beginning of each test. Lower
the basket into position before rotation. Operate the apparatus immediately at the speed of rotation 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 surface of the dissolution medium and the top of the rotating blade or basket, not less than 10mm
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 samples 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 ingredient in 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 solution per tablet or capsules and calculate as a percentage of the stated amount. If the results do not
conform to the requirements at stage S1 given in the accompanying acceptance table (Table 1), continue testing with
additional tablets or capsules through stages S2 and S3 unless the result conform at stage S2.
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 the dissolution medium. Perform the analysis as directed
in the individual monograph. Make any necessary correction.
Correction factors should not be greater than 25% of the stated amount.
TABLE 1- Acceptance Table

Stage

Number Tested

Acceptance
Each unit is not less than D* + 5%

S1

S2

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 t or greater than D, not, More than 2 units are
less than D - 15% and no unit is less than D - 25%

Theories of dissolution: Some workers have reviewed the factors which can affect the dissolution of tablets and these
include the stirring speed, temperature, viscosity, pH, composition of the dissolution medium and the presence or
absence of wetting agents.
Physical models have been set up to account for the observed dissolution of tablets. According to Higuchi50, there are
three models which either alone or in combination, can be used to describe the dissolution mechanisms. These are:
The Diffusion layer model: This model (Fig 2) assumes that a layer of liquid, H cm thick, adjacent to the solid surface
remains stagnant as the bulk liquid passes over the surface with a certain velocity. The reaction at the solid/liquid
interface is assumed to be instantaneous forming a saturated solution, Cs, of the solid in the static liquid film. The
rate of dissolution is governed entirely by the diffusion of the solid molecules from the static liquid film to the
bulk liquid according to Ficks first law:
J = - Df dc / dx (4)
Where J is the amount of substance passing perpendicularly through a unit surface area per time, Df ,is the diffusion
coefficient and dc / dx, is the concentration gradient. After a time t, the concentration between the limit of the static liquid
layer and the bulk liquid becomes Ct. Once the solid molecules pass into the bulk liquid, it is assumed that there is rapid
mixing and the concentration gradient disappears.

The theory predicts that if the concentration gradient is always constant i. e. Cs - Ct is constant because Cs >> Ct (sink
conditions which usually mean Cs > 10 Ct) then a uniform rate of dissolution is obtained.

Fig. 2. Diffusion Layer Model

The Interfacial Barrier Model: In the interfacial barrier model (Fig 3), it is assumed that the reaction at the solid/liquid
interface is not instantaneous due to a high activation free energy barrier which has to be surmounted before the
solid can dissolve. Thereafter the dissolution mechanism is essentially the same as in (i) above, with the
concentration at the limit of the static layer of liquid becoming Ct after time t.
The rate of diffusion in the static layer is relatively fast in comparison with the surmounting of the energy barrier, which
therefore becomes rate limiting in the dissolution process.

Fig. 3. Diagrammatic representation of the free energy barrier to dissolution

The Danckwerts Model: The Danckwerts model (Fig 4) assumes that macroscopic packets of solvent reach the
solid/liquid interface by eddy diffusion in some random fashion.

Fig. 4. The Danckwerts Model.

At the interface, the packet is able to absorb solute according to the laws of diffusion and is then replaced by a new packet
of solvent. This surface renewal process is related to the solute transport rate and hence to the dissolution rate.
The rate laws predicted by the different mechanisms both alone and in combination, have been discussed by Higuchi.

However, the earliest equation expressing dissolution rate in a quantitative manner was proposed by Noyes and Whitney
as:dc / dt = k (Cs - Ct) ------- (5)
Where dc / dt is the rate of change in concentration with respect to time, and k is the rate constant. The integrated form of
the equation is:
In [Cs / (Cs - Ct) ] = kt -------- (6)
The equation in resemblance to the other rate law equations, predicts a first order dependence on the concentration
gradient (i.e. Cs - Ct ) between the static liquid layer next to the solid surface and the bulk liquid. Noyes and Whitney
explained their dissolution data using a concept similar to that used for the diffusion model. This considerations relate to
conditions in which there is no change in the shape of the solid during the dissolution process ( i. e. the surface area
remains constant). However, for pharmaceutical tablets, disintegration occurs during the dissolution process and the
surface area generated therefore varies with time.
Aguiar et al proposed a scheme which holds that dissolution occurs only when the drug is in small particles.
Wagnermodified this idea and showed that dissolution occurs from both the intact tablet and the aggregates and/or
granules produced after disintegration by using a plot of the percentage of drug dissolved versus time on logarithmic probability graph papers.
A modification of this approach was proposed by Kitazawa et al. Employing the integrated form of Noyes and Whitney
equation (equation 6), they determined the dissolution rate constant of uncoated caffeine tablets. The Kitazawa equations
have been used to determine the dissolution rates of some pharmaceutical tablet formulations.
(3) Weight variation OR Uniformity of weight: This test is not applicable to coated tablets other than film-coated
tablets and to tablets that are required to comply with the test for uniformity of content for all active ingredients.
Weigh 20 tablets selected at random and calculate the average weight. Not more than two of the individual weights
deviate from the average weight by more than the percentage shown in Table 2 and none deviates by more than twice that
percentage.
IP Standard:
Average weight of tablet
80 mg or less

Percentage deviation
10

More than 80 mg but less than 250 mg

7.5

250 mg or more

USP Standard:
Average weight

Percent difference

130mg or less

10

More than 130mg through 324mg

7.5

More than 324mg

(4) Content uniformity: The content uniformity test is used to ensure that every tablet contains the amount of drug
substance intended with little variation among tablets within a batch. Due to increased awareness of physiological
availability, the content uniformity test has been included in the monographs of all coated and uncoated tablets and all
capsules intended for oral administration where the range of size of the dosage form available include 50mg or smaller
sizes. Tablet monographs with a content uniformity requirement do not have weight variation requirements

USP Standard: For content uniformity test, representative samples of 30tablets are selected and 10 are assayed
individually. At least 9 must assay within 15% of the declared potency and none may exceed 25%
IP Standard: This test is applicable to tablets that contain less than 10 mg or less than 10% w/w of active ingredient. For
tablets containing more than one active ingredient carry out the test for each active ingredient that corresponds to the
aforementioned conditions. Determine the content of active ingredient(s) in each of 10 tablets taken at random using the
method given in the monograph or by any other suitable analytical method. The tablets comply with the test if not more
than one of the individual values thus obtained is outside the limits 85 to 115% of the average value and none is outside
the limits 75 to 125% of the average value. If two or three of the individual values are outside the limits 85 to 115% of the
average value and none is outside the limits 75 to 125%, repeat the determination using another 20 tablets. The tablets
comply with the test if in the total sample of 30 tablets not more than three of the individual values are outside the limits
85 to 115% and none is outside the limits 75 to 125% of the average value.