I-Disintegration This test is provided to determine whether tablets or capsules disintegrate within the prescribed time when placed in a liquid medium at the experimental conditions presented below. Compliance with the limits on Disintegration stated in the individual monographs is required except where the label states that the tablets or capsules are intended for use as troches, or are to be chewed, or are designed as extended- release dosage forms or delayed-release dosage forms. Determine the type of units under test from the labeling and from observation, and apply the appropriate procedure to 6 or more dosage units
PROCEDURE Uncoated Tablets— Place 1 dosage unit in each of the six tubes of the basket and, if prescribed, add a disk. Operate the apparatus, using water or the specified medium as the immersion fluid, maintained at 37 ± 2. At the end of the time limit specified in the monograph, lift the basket from the fluid, and observe 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. The requirement is met if not fewer than 16 of the total of 18 tablets tested are disintegrated.
Disintegration apparatus. (All dimensions are expressed in mm.)
II-Dissolution Definition- Dissolution is a process in which a solid substance solubilizes in a given solvent i.e. mass transfer from the solid surface to the liquid phase. Rate of dissolution is the amount of drug substance that goes in solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition.
The rate of dissolution is given by Noyes and Whitney: Where, dc/dt= dissolution rate of the drug K= dissolution rate constant C s = concentration of drug in stagnant layer C b = concentration of drug in the bulk of the solution at time t = k (C s - C b ) dc dt 6
Conc. of dissolved drug Time first order dissolution under non-sink condition zero order dissolution under sink condition Dissolution rate under non-sink and sink conditions. 7
Dissolution test 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 I 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 II 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 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. Take samples at the prescribed time. Withdraw the samples from a point half-way between the surface of the dissolution medium and the top of the rotating basket or blade, not less than 10 mm from the wall of the vessel. Add a volume of dissolution medium equal to the volume of the samples withdrawn or compensate by calculation. Filter the samples at 36.5° to 37.5° and determine the amount of active ingredient present by the method prescribed in the individual monograph.. Repeat the complete operation five times.
Rotating Basket Apparatus (Apparatus 1) It is basically a closed-compartment, beaker type apparatus. It comprising of a cylindrical glass vessel with hemispherical bottom of one litre capacity partially immersed in a water bath. A cylindrical basket made of #22 mesh is located centrally in the vessel at a distance of 2 cm from the bottom and rotated by a variable speed motor through a shaft. 9
Contd….. All metal parts like basket and shaft are made of stainless steel 316.
Rotating Paddle Apparatus (Apparatus 2) Here, basket is replaced with a stirrer. A small, loose, wire helix may be attached to the dosage form that would otherwise float. The position and alignment of the paddle are specified in the official books.
stageNumb er tested Acceptance criteria S1S1 6Each unit is not less than Q + 5% S2S2 6 1- Average of the12 units (S 1 + S 2 ) is equal to or greater than Q 2- No unit is less than Q – 15% S3S3 121.average of the 24units (S 1 + S 2 + S 3 ) is equal to or greater than Q 2.not more than 2 units are less than Q – 15% 3.no unit is less than Q – 25% Acceptance table
Weight and Hardness Variation: Weight and hardness variation are common problems experienced when tableting. Tablet weight is mainly affected by factors such as powder variation, tablet press condition and tooling, and flow of powder on the tablet press.
Inconsistent powder or granulate density and particle size distribution are common sources of weight variation during tablet compression. Problems related to the density of the powder or granulate are often associated with overfilling of the die and recirculation of the product on the tablet press. A variation of particle size distribution of the powder or granulate can be the result of segregation due to transfer or static electricity
Weight variation can arise as a result of a poorly prepared or operated tablet press. Inspection of the critical dimensions of tablet press tools is recommended During the course of a compression operation it is also important to not neglect the level of the product in the hopper. Head pressure is a critical factor related to the amount of product in the hopper
III – uniformity of dosage units 1- Content uniformity test: it is required for the: Uncoated tablets containing less than 50 mg of an active ingredient comprising less than 50% of the weight of one dosage unit. 2-Weight variation test: it is required for the: Uncoated tablets containing 50 mg or more of an active ingredient comprising 50% or more of the weight of one dosage unit.
1- Content uniformity test Method 1- Select not less than 30 units 2-Assay 10 units individually as directed in the assay in the individual monograph. 3- From the assay, calculate the content of active ingredient in each unit. 4- Calculate X i = (content/L.C)*100 5- Calculate X ¯ = ∑ X i / n ( NO. of tablets tested) 6- Calculate standard deviation (S) = [(X i - X ¯ ) 2 / (n – 1)] ½ 7- Calculate (Relative standard deviation) RSD = (S / X ¯ )*100
2-Weight variation test Method: weigh accurately 10 tablets individually From the assay, calculate the average content % then calculate the content of active ingredient in each capsule. Calculate X i = (content/L.C)*100 Calculate X ¯ = ∑ X i / n ( NO. of tablets tested) Calculate standard deviation (S) = [(X i - X ¯ ) 2 / (n – 1)] ½ Calculate RSD ( Relative standard deviation) = ( S / X ¯ )*100
Criteria: Accepted if: the amount of X i of the 10 tablets lies within the range of 85% to 115% And RSD of the 10 tablets is less than or equal to 6%. Suspected if: One X i is outside the range 85% to 115% but not outside the range of 75% to 125%. Or RSD is greater than 6% Or both conditions. Test 20 another 20 tablets Accepted if: – Not more than one X i of 30 X i are outside the range of 85% to 115% – None outside the range of 75% to 125%. – RSD of the 30 tablets is less than or equal to 7.8 %.
IV- Friability (measure of tablet resistance to abrasion)
Reasons of tablet friability Hardness variation Capping and lamination Low moisture content in tablets Low binder efficiency
For tablets with a unit weight equal to or less than 650 mg, take a sample of whole tablets corresponding as near as possible to 6.5 g. For tablets with a unit weight of more than 650 mg,take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before, and accurately weigh. Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablet sample after tumbling, the sample fails the test. If the results are difficult to interpret or if the weight loss is greater than the targeted value, the test should be repeated twice and the mean of the three tests determined. A maximum mean weight loss from the three samples of not more than 1.0% is considered acceptable for most products