Hardness Test

Hardness is also so called crushing strength. It is the load required to crush the tablet when placed on its edge. There are a variety of presentations for tablets as delivery systems for pharmaceutical agents, such as rapidly disintegrating, slowly disintegrating, eroding, chewable, and lozenge. Each of these presentations places a certain demand on the bonding, structure, and integrity of the compressed matrix. Tablets must be able to withstand the rigors of handling and transportation experienced in the manufacturing plant, in the drug distribution system, and in the field at the hands of the end users (patients/consumers). Manufacturing processes such as coating, packaging, and printing can involve considerable stresses, which the tablets must be able to withstand. For these reasons, the mechanical strength of tablets is of considerable importance and is routinely measured. Tablet strength serves both as a criterion by which to guide product development and as a quality control specification.

Measure of the mechanical integrity of tablets is their breaking force, which is the force required to cause them to fail (i.e., break) in a specific plane. The tablets are generally placed between two platens, one of which moves to apply sufficient force to the tablet to cause fracture. For conventional, round (circular cross-section) tablets, loading occurs across their diameter (sometimes referred to as diametral loading), and fracture occurs in that plane.

The breaking force of tablets is commonly called hardness in the pharmaceutical literature (“hardness is defined as the resistance of the tablet against the applied force till it breaks”); however, the use of this term is misleading. In material science, the term hardness refers to the resistance of a surface to penetration or indentation by a small probe. The term crushing strength is also frequently used to describe the resistance of tablets to the application of a compressive load. Although this term describes the true nature of the test more accurately than does hardness, it implies that tablets are actually crushed during the test, which often is not the case. Moreover, the term strength in this application can be questioned, because in the physical sciences that term is often used to describe a stress (e.g., tensile strength). Thus, the term breaking force is preferred.



Why do we measure hardness?
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 batch . And if the disintegration is within limit, we accept the batch.

If H. is high + disintegration is within time è accept the batch.

APPARATUS FOR MEASURING HARDNESS

1. Monsanto Hardness Tester or Stokes Hardness tester (1930).

2. Pfizer Hardness Tester (1950).

3. Strong cob Hardness Tester.

4. Heberlain Hardness Tester or Schleeniger Hardness tester.

Early measuring devices were typically hand operated. For example, the Monsanto (or Stokes) hardness tester was based on compressing tablets between two jaws via a spring gauge and screw. In the Pfizer hardness tester, the vertically mounted tablet was squeezed in a device that resembled a pair of pliers. In the Strong Cobb hardness tester, the breaking load was applied through the action of a small hydraulic pump that was first operated manually but was later motorized. Problems associated with these devices were related to operator variability in rates of loading and difficulties in proper setup and calibration. Modern testers employ mechanical drives, strain gauge–based load cells for force measurements, and electronic signal processing, and therefore are preferred.

However, the result of Strong cob hardness tester is 1.6 times accurate than the Heberlain hardness tester and 1.4 times more accurate than the Pfizer hardness tester.

Most commonly used apparatus for hardness is electronically operated hardness tester i.e. HEBERLAIN HARDNESS TESTER.

HEBERLAIN HARDNESS TESTER:

This apparatus usually have two platens between which tablets is placed and compressed and the value of the hardness is measured. The platens should be parallel. Their faces should be polished smooth and precision-ground perpendicularly to the direction of movement. Perpendicularity must be preserved during platen movement, and the mechanism should be free of any bending or torsion displacements as the load is applied. The contact faces must be larger than the area of contact with the tablet.

Either the rate of platen movement or the rate at which the compressive force is applied (i.e., the loading rate) should be constant. Maintaining a constant loading rate avoids the rapid buildup of compressive loads, which may lead to uncontrolled crushing or shear failure and greater variability in the measured breaking force. However, constant loading rate measurements may be too slow for real time monitoring of tablet production.

UNIT of measuring hardness is kg/cm2.

CRITERA: Tablet hardness should lies between 5 to 10 kg/cm2.

RESULT LIMIT: ± 5%.

Thickness and diameter of the tablets can also be checked by this Heberlain hardness tester. The mode of the apparatus is set according to the test (hardness, thickness or diameter

Factors Affecting the Hardness:

Compression of the tablet and compressive force. 

Amount of binder. (More binder à more hardness) 

Method of granulation in preparing the tablet (wet method gives more hardness than direct method, Slugging method gives the best hardness).

Limits:

5 kilograms minimum and 8 kilograms maximum.

Make hardness test on 5 tablets and then take the average hardness

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Content Uniformity

Content Uniformity Testing is useful for assessing the consistency of:

Powder blends before filling or compressing

Semi-solid and liquid bulk batches before filling

Filling during manufacturing (such as powders into capsules or liquids into vials or bottles)

Active content within individual units post-manufacturing (such as individual tablets after compression)

Content uniformity testing involves using a content/potency assay to determine the content of active material contained in multiple different samples collected throughout the batch.

Examples of sample sets that may be collected for content uniformity determinations are:

Tablets from the beginning, middle and end of a compression run. Aliquots of bulk material taken from the top, middle and bottom of a vessel before filling. Randomly selected bottles filled with a liquid taken out of a packaged case.Randomly selected capsules taken from a single bottle representing 10% of the number of capsules filled into the bottle.

Procedure:

Select 10 capsules or tablets at random. If using capsules empty contents of each capsule carefully in a suitable container. Using a suitable analytical method, assay the individual content of the active ingredient in each capsule or tablet.

The preparation complies if not more than one (all within limits) individual content is outside the limits of 85 to 115 % of the average content and none is outside the limits of 75 to 125 % of the average content. The preparation fails to comply with the test if more than 3 individual contents are outside the limits of 85 to 115 % of the average content or if one or more individual contents are outside the limits of 75 % to 125 % of the average content. According to INDIAN PHARMACOPOIEA Content of active ingredients. Determine the amount of active ingredient(s) by the method described in the Assay and calculate the amount of active ingredient(s) in each capsule. The result lies within the range for the content of active ingredient(s) stated in the monograph. This range is based on the requirement that 20 capsules, or such other number as may be indicated in the monograph, are used in the Assay. Where 20 capsules cannot be obtained, a smaller number, which must not be less than 5, may be used, but to allow for sampling errors the tolerances are widened in accordance with Table 1. The requirements of Table 1 apply when the stated limits are between 90 and 110 per cent. For limits other than 90 to 110 per cent, proportionately smaller or larger allowances should be made Weigh of Active Subtract Weigh of Active ingredients in each Capsules. The table is given in IP.

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Assay

An assay is an investigative (analytic) procedure in laboratory medicine, pharmacology, environmental biology, and molecular biology for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity (the analyte) which can be a drug or biochemical substance or a cell in an organism or organic sample.Generally in an assay the quantity of the exogenous materials (the reagents) are kept fixed (or in excess) so that the quantity (and quality) of the target is the only limiting factor for the reaction/assay process, and the difference in the assay outcome is used to deduce the unknown quality or quantity of the target in question. Some assays (e.g., biochemical assays) may be similar to or have overlap with chemical analysis and titration. But generally assays involve biological material or phenomena which tend to be intrinsically more complex either in composition or in behavior or both. Thus reading of an assay may be quite noisy and may involve greater difficulties in interpretation than an accurate chemical titration. On the other hand older generation qualitative assays especially bioassays may be much more gross and less quantitative (e.g., counting death or dysfunction of an organism or cells in a population, or some descriptive change in some body part of a group of animals).
An assay (analysis) is never an isolated process and needs to be preceded by certain necessary procedures which are the preanalytic steps and must be followed by certain necessary post analytic steps. The information communication (eg request to perform an assay and further information processing) or specimen handling (eg collection transport and processing) done before and till the point of beginning of an assay are the preanalytic steps. Similarly after the actual assay is done the result may be documented, verified and transmitted/communicated in steps which are called post-analytic steps related to an assay. Like any multistep information handling and transmission systems, variation and errors in the communicated final results of an assay involves corresponding parts in every such step ie not only analytic variations and errors intrinsic to the assay itself but also variations and errors involved in preanalytic and post analytic steps. Since the assay itself (the analytic step) gets a lot of attention, steps that get less attention by the chain of users ie the preanalytic and the post analytic steps are often less stringently regulated and generally more prone to errors- eg preanalytic steps in medical laboratory assays may contribute to 32-75% of all lab errors

Example of Assay of Tetracycline.



Requirement:
Pipette, volumetric flask, beaker, measuring cylinder, and watch glass

Label claim:
25mg/capsule

Official Limits:
95% – 105%
?
?

Procedure:
Dissolve the content of 1 capsule in 50ml of N/10 HCl in 100ml of volumetric flask and make up the volume up to 1000ml with N/10 HCl. This is 1st dilution pipette out 5ml from solution into another volumetric flask and make up the volume up to 100ml with distill water. This is second dilution. Now collect 10ml from solution. Put it In volumetric flask and add 60ml of distill water and 10ml of N/10 NaOH. It should be added at time of measuring the absorbance because it is time dependent reaction. Now make up the volume up to 100ml with distill water. This is final dilution. Measure the absorbance of resultant solution at 380nm taking as ? . determine the constant of capsule by using formula
Percentage purity:

Preparation of N/10 NaOH:
Dissolve 0.4g of NaOH in 00ml of distill water.

Preparation of N/10 HCl:
Dissolve 0.85ml of HCl in 100ml of distill water.

Result:
The percentage purity of given sample of tetracycline capsule is 100.8% by spectrophotometer.

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Disintegration

Disintegration is a state in which no residues except fragments of un-dissolved coating remain on the screen of test apparatus. If any residue left, it must consists of soft mass having no palpably firm un-moistened core.

 Purpose:

This is the test that is used to check whether your dosage form will disintegrate within the prescribed time when placed in liquid under prescribed experimental conditions.

Components:

1.      Beaker

2.      Thermostat

3.      Lever

4.      Basket/ Rack assembly

5.      Disk

Beaker:

It is 1 litter low form beaker for immersion fluid.

Thermostat:

There is an arrangement in the apparatus for heating the fluid to 35-39 Celsius. It is called thermostat.

Lever:

It is the device for lowering and elevating the basket rack assembly in the emersion fluid at constant frequency of 29-32 cycles per minutes through a distance of 55mm. The volume of the immersion fluid is such that at upward stroke the mesh of basket rack is 15 ±2 mm and at the downward stroke the mesh of the basket track assembly should be 25 mm above the bottom of the vessel. The time required for upward stroke is equal to time required for the downward stroke and there is no abrupt reversal of motion.  

Basket rack assembly:

It consists of six open enabled, transparent tubes. These are held in vertical position by two plates, each plate have six holes on the plate at upper side of the tube and second is at the lower side of the tube. The parts if the basket rack assembly is assembled together by two boards passing through these plates. There is a stainless steel cloth below the lower plate with mesh side 2± 1.8, 2.2 mm. The design of basket rack assembly can be varied can be changed, if dimension of mesh and tubes held constant.

Disk:

Six slatted and perforated disks with 5 holes can be used in the apparatus. It is permitted in the individual monograph. The disk is made of suitable transparent plastic material having specific gravity between 1.18 to 1.2.

Procedure:

Uncoated tablets:

Place one tablet in each of the 6 tubes of basket rack assembly using a disk if permitted in the monograph. Operate the apparatus using water specified medium as the immersion fluid at T of 37 ±2 Celsius. At the end of time in the monograph lift the basket from immersion fluid and observe tablets. All the tablets should be disintegrated. If 1 or 2 tablets fail to disintegrate repeat the procedure on addition of 12 tablets. Not less than 16 out of 18 tablets should be disintegrated.

Plane coated tablets:

Apply the test for the monocoated tablets by operating the apparatus for the specified time for the individual monograph. You will have to do the same procedure given above but the time for the monocoated tablets will be different.

Enteric coated tablets:

Place one tablet in each of the 6 tubes. If the tablet has the soluble external coating then immense the tablets at room temperature in water for 5 minutes then operate the apparatus using the stimulated gastric fluid as the immersion fluid for one hour. After one hour lift the plate from the basket and see if there are any signs of the softening. There must be no softening then operate the procedure again for with the stimulated intestinal fluid environment for the specific time as specified in the monograph for one hour. All the tablets should have disintegrated. At the end of time in the monograph lift the basket from immersion fluid and observe tablets. All the tablets should be disintegrated. If 1 or 2 tablets fail to disintegrate repeat the procedure on addition of 12 tablets. Not less than 16 out of 18 tablets should be disintegrated.

Buckle tablets:

Apply the test for the uncoated tablets and after four hours lift the basket from the immersion fluid and observe disintegration. At the end of time in the monograph lift the basket from immersion fluid and observe tablets. All the tablets should be disintegrated. If 1 or 2 tablets fail to disintegrate repeat the procedure on addition of 12 tablets. Not less than 16 out of 18 tablets should be disintegrated.

Sublingual tablets:

Apply the test for the uncoated tablets. After the specified time lift the basket from the immersion fluid. At the end of time in the monograph lift the basket from immersion fluid and observe tablets. All the tablets should be disintegrated. If 1 or 2 tablets fail to disintegrate repeat the procedure on addition of 12 tablets. Not less than 16 out of 18 tablets should be disintegrated.

Gelatin capsule:

Place one capsule in each of 6 tubes. Place stainless steel woven cloth at the upper side of the plate and operate the apparatus. After the time specified in the individual monograph lift the basket and observe the capsules. All of the capsules have disintegrated. At the end of time in the monograph lift the basket from immersion fluid and observe tablets. If 1 or 2 capsules fail to disintegrate repeat the procedure on addition of 12 capsules. Not less than 16 out of 18 capsules should be disintegrated.

Types of tablets	Disintegration time
Soluble tablets	3 minutes
Effervescence tablets	5 minutes
Uncoated tablets	15 minutes
Film coated tablets	30 minutes
Sugar coated tablets	60 minutes
Enteric coated tablets	2 to 3 hours

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