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1. 1. TABLETS General chapter
2. 2. TABLETS • Tablets are solid dosage form each containing a unit dost of one or more medicament • Intended for oral administration • Some tablets are swallowed whole or after being chewed • some are dissolved or dispersed in water before administration • some are retained in the mouth where the active ingredient is liberated.
3. 3. TABLETS • Because of their composition, method of manufacture or intended use, tablets present a variety of characteristics and consequently there are several categories of tablets. • Unless otherwise stated in the individual monograph, tablets are uncoated.
4. 4. Different types of tablets • Uncoated tablets • Film Coated • Sugar Coated • Dispersible Tablets • Effervescent Tablets • Modified-release Tablets • Enteric-coated Tablets • Prolonged- release Tablets • Soluble Tablets • Tablets for Use in the Mouth
5. 5. In-process Tests • Uniformity of container contents • Content of active ingredients • Uniformity of content • Uniformity of weight • Dissolution • Disintegration • Friability • Hardness • Leak test Pharmacopoial Non- Pharmacopoial
6. 6. Uniformity of container contents / Contents of Packaged Dosage Forms (IP) • The following tests and specifications apply to oral dosage forms and preparations intended for topical use that are packaged in containers in which the labeled net quantity is not more than 100 g or 300 ml or 1000 units, as the case may be • For higher labeled quantities the test and limits given in the standards of Weights and Measures (Packaged commodities) Rules, 1977 may be followed.
7. 7. Contents of Packaged Dosage Forms • Test Method • Select a sample of 10 containers and count the number of tablets in each container. • The average number of the contents in the 10 containers is not less than the labeled amount and the number in any single container is not less than 98 per cent and not more than 102 per cent of the labeled amount • If this requirements is not met, count the number of the contents in 10 additional containers. The average number in the 20 containers is not less than the labeled amount, and the number in not more than 1 of the 20 containers is less than 98 per cent or more than102 per cent of the labeled amount.
8. 8. • This test is applicable to tablets that contain 10 mg or less than 10 mg or less than 10 per cent w/w of active ingredient (As per IP). • This test is applicable to tablets that contain less than 25 mg or less than 25 per cent w/w of active ingredient (As per BP/USP ). • For tablets containing more than one active ingredient carry out the test for each active ingredient that corresponds to the aforementioned conditions. • The test is also applicable to coated tablets other than film coated tablets, irrespective of their content of active substance(s). • The test for Uniformity of content should be carried out only after the content of active ingredient(s) in a pooled sample of the tablets has been shown to be within accepted limits of the stated content. • The test for Uniformity of content is not applicable to tablets containing multivitamins and trace elements. Uniformity of content
9. 9. • The test for uniformity of content of single-dose preparations is based on the assay of the individual contents of active substance(s) of a number of single- dose units to determine whether the individual contents are within limits set with reference to the average content of the sample. • Method. • Determine the content of active ingredient(s) in each of 10 dosage units taken at random using the method given in the monograph or by any other suitable analytical method. • Acceptance limits • The preparation complies with the test if each individual content is 85 to 115 per cent of the average content. The preparation fails to comply with the test if more than one individual content is outside these limits or if one individual content is outside the limits of 75 to 125 per cent of the average content. Uniformity of content
10. 10. • If one individual content is outside the limits of 85 to 115 percent of the average content but within the limits of 75 to 125 per cent, repeat the determination using another 20 dosage units. The preparation complies with the test if not more than one of the individual contents of the total sample of 30 dosage units is outside 85 to 115 per cent of the average content and none is outside the limits of 75 to 125 per cent of the average content. Uniformity of contents
11. 11. Uniformity of Weight of Single-Dose Preparations (IP/BP/USP) • Weigh individually 20 units selected at random or, for single dose preparations in individual containers, the contents of 20 units, 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 the table and none deviates by more than twice that percentage.
12. 12. Disintegration Test • For the purpose of this test, disintegration does not imply complete solution of the dosage unit or even of its active constituent. • Disintegration is defined as that state in which no residue of the unit under test remains on the screen of the apparatus or, if a residue remains, it consists of fragments of disintegrated parts of capsule component parts such as insoluble coating of the of capsule shells, or of any melted fatty substance from the pessaries or suppository 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 consists only of fragments of shells. • 28-32 cycle (strokes) per minute IP • 29-32 cycle (strokes) per minute BP/USP
13. 13. Method • Unless otherwise stated in the individual monograph, introduce one tablet 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 1 or 2 tablets or capsules fail to disintegrate, repeat the test on 12 additional tablets or capsules; not less than 16 of the total of 18 tablets or capsules tested disintegrate. • If the tablets or capsules adhere to the disc and the preparation under examination 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.
14. 14. For enteric-coated tablets • Method. • If tablets having soluble external sugar coating, immerse the basket in water at room temp for 5 min (USP). • Put one tablet into each tube, suspend the assembly in the beaker containing 0.1M hydrochloric acid and operate without the discs for (2 hour as per IP/BP) (1 hour as per USP) , 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 and operate the apparatus for a further 60 minutes. • Remove the assembly from the liquid. If the tablet fails to comply because of adherence to the disc, repeat the test on a further 6 tablets without the discs. The tablets pass the test if all six have disintegrated.
15. 15. Disintegration testing condition and interpretation (IP) Sr. No Type of tablets Medium Temperatu re Limit 1 Uncoated Water/buffer 37 °± 2 °C 15 min or as per individual monograph 2 Film coated Water 37 °±2 °C 30 min or as per individual monograph 3 Sugar coated Water/0.1 N HCl 37 °±2 °C 60 min or as per individual monograph 4 Dispersible Tablets Water 25 °±1 °C 03 min or as per individual monograph 5 Effervescent Tablets Water 25 °±5 °C 05 min or as per individual monograph 6 Enteric-coated Tablets 0.1 M HCl mixed phosphate buffer pH 6.8 37 °±2 °C 02 hour in HCl: no disintegration 60 min in buffer : disintegrate 7 Soluble Tablets Water 20 °±5 °C 03 minutes
16. 16. Disintegration testing condition and interpretation (BP) Sr. No Type of tablets Medium Temperatu re Limit 1 Uncoated Water/buffer 37 °± 2 °C 15 min or as per individual monograph 2 Film coated Water 37 °±2 °C 30 min or as per individual monograph 3 Sugar coated Water/0.1 N HCl 37 °±2 °C 60 min or as per individual monograph 4 Dispersible Tablets Water 20 °±5 °C 03 min or as per individual monograph 5 Effervescent Tablets Water 20 °±5 °C 05 min or as per individual monograph 6 Enteric-coated Tablets 0.1 M HCl mixed phosphate buffer pH 6.8 37 °±2 °C 02 hour in HCl: no disintegration 60 min in buffer : disintegrate 7 Soluble Tablets Water 20 °±5 °C 03 minutes
17. 17. Disintegration testing condition and interpretation (USP) Sr. No Type of tablets Medium Temperatu re Limit 1 Uncoated Water/as specified in monograph 37 °± 2 °C As per individual monograph 2 Coated Water/as specified in monograph 37 °±2 °C As per individual monograph 4 Enteric-coated Tablets Simulated gastric fluid TS Simulated intestinal fluid TS 37 °±2 °C 01 hour in Simulated gastric fluid TS: No disintegration As per individual monograph: Simulated intestinal fluid TS 5 Buccal Tablets Water/as specified in monograph 37 °± 2 °C 4 hour 6 Sublingual tablets Water/as specified in monograph 37 °± 2 °C As per individual monograph
18. 18. Dissolution Test • Use Apparatus 1 unless otherwise directed. • 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. • 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 per cent.
19. 19. • Assemble the apparatus and warm the dissolution medium to 36.5 ° to 37.5 °C unless otherwise stated • 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 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 samples withdrawn. • Perform the analysis as directed in the individual monograph.
20. 20. Acceptance criteria Conventional-release dosage forms (IP) • Unless otherwise specified, the requirements are met if the quantities of active substance dissolved from the dosage units conform to Table below . If the results do not conform to the requirements at stage S1 given in the table, continue testing with additional dosage units through stages S2 and S3 unless the results conform at stage S2.
21. 21. As per IP
22. 22. Acceptance criteria • Conventional-release solid dosage forms (BP/USP) • Unless otherwise specified, the requirements are met if the quantities of active substance dissolved from the dosage units tested conform to Table below. Continue testing through the 3 levels unless the results conform at either S1 or S2. • The quantity Q, is the specified amount of dissolved active substance, expressed as a percentage of the labeled content; the 5 per cent, 15 per cent, and 25 per cent values in the Table are percentages of the labeled content so that these values and Q are in the same terms.
23. 23. As per (BP/USP)
24. 24. Immediate release dosage form pooled sample (USP) • Unless otherwise specified, the requirements are met if the quantities of active substance dissolved from the pooled sample conform to Table of pooled sample below. • If the results do not conform to the requirements at stage S1 given in the table, continue testing with additional dosage units through stages S2 and S3 unless the results conform at stage S2. • The quantity Q is the amount of dissolved active ingredient specified in the individual monograph, expressed as a percentage of the labeled content
25. 25. As per USP
26. 26. Prolonged-release dosage forms (IP) • Unless otherwise specified, the requirements are met if the quantities of active substance dissolved from the dosage units conform to Table below. • If the results do not conform to the requirements at stage L1 given in the table, continue testing with additional dosage units through stages L2 and L3 unless the results conform at stage L2. • The limits embrace each value of D, the amount dissolved at each specified dosing interval. • Where more than one range is specified, the acceptance criteria apply to each range.
27. 27. Prolonged-release dosage forms (BP/USP) • Unless otherwise specified, the requirements are met if the quantities of active substance dissolved from the dosage units tested conform to Table below. • Continue testing through the 3 levels unless the results conform at either L1 or L2. • Limits on the amounts of active substance dissolved are expressed in terms of the percentage of labeled content. The limits embrace each value of Qi, the amount dissolved at each specified fractional dosing interval. Where more than one range is specified, the acceptance criteria apply individually to each range.
28. 28. Modified-release dosage forms (IP) There are 2 method A & B Method A & B Acid stage. • 750 ml/1000 ml of 0.1M hydrochloric acid • 36.5º to 37.5º. • 2 hours • Perform the analysis of the aliquot using a suitable assay method. Buffer stage. • Complete the operations of adding the buffer and adjusting the pH within 5 minutes. • 250 ml of a 0.2 M buffer and solution • 36.5º to 37.5º. • 6.8 ± 0.05 • 45 minutes, or for the specified time.
29. 29. Acceptance criteria (IP) • ACID STAGE • The requirements of the test are met if conform to Table below. Continue the testing through the 3 levels unless the results of both acid and buffer stages conform at an earlier level
30. 30. Acceptance criteria (IP) • BUFFER STAGE • The requirements of the test are met if conform to Table below. Continue the testing through the 3 levels unless the results of both acid and buffer stages conform at an earlier level • The value of D in Table is 75 per cent dissolved unless otherwise specified. • The quantity, D, is the specified total amount of active substance dissolved in both the acid and buffer stages, expressed as a percentage of the labeled content.
31. 31. Prolonged-release solid dosage forms (BP/USP) There are 2 method A & B Method A & B Acid stage. • 750 ml/1000 ml of 0.1M hydrochloric acid • 36.5º to 37.5º. • 2 hours • Perform the analysis of the aliquot using a suitable assay method. Buffer stage. • Complete the operations of adding the buffer and adjusting the pH within 5 minutes. • 250 ml of a 0.2 M buffer and solution • 36.5º to 37.5º. • 6.8 ± 0.05 • 45 minutes, or for the specified time.
32. 32. Acceptance criteria (BP/USP) • ACID STAGE • Unless otherwise specified, the requirements of this portion of the test are met if the quantities, based on the percentage of the labeled content of active substance dissolved from the units tested conform to Table 2.9.3.-3. Continue testing through the 3 levels unless the results of both acid and buffer stages conform at an earlier level.
33. 33. Acceptance criteria (BP/USP) • BUFFER STAGE • The requirements are met if active substance dissolved from the units tested conform to Table 2.9.3.-4. • Continue testing through the 3 levels unless the results of both stages conform at an earlier level. • The value of Q in Table 2.9.3.-4 is 75 per cent dissolved unless otherwise specified. • The quantity, Q, is the specified total amount of active substance dissolved in both the acid and buffer stages, expressed as a percentage of the labeled content. • The 5 per cent, 15 per cent and 25 per cent values in the Table are percentages of the labeled content so that these values and Q are in the same terms.
34. 34. Dissolution testing condition and interpretation (IP) Sr. No Type of tablets Medium Temperature Limit 1 Uncoated Water/buffer 37 °± 5 °C As per tables shown before or As per individual monograph 2 Film coated Water 37 °±5 °C As per tables shown before or As per individual monograph 3 Sugar coated Water/0.1 N HCl 37 °±2 °C As per tables shown before or As per individual monograph 4 Enteric-coated Tablets 0.1 M HCl & Mixed phosphate buffer pH 6.8 37 °±2 °C 02 hour in HCl & 60 min in buffer As per tables shown before or As per individual monograph 5 Prolonged- release Tablets Water/buffer 37 °±2 °C As per tables shown before or As per individual monograph
35. 35. Uniformity of dispersion • Applied to Dispersible Tablets • Method: • 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 mm (sieve number 22).
36. 36. Friability of Uncoated Tablets• This test is applicable to compressed tablets and is intended to determine the physical strength of tablets. • Apparatus. • A drum of transparent synthetic polymer with polished internal surfaces • Diameter of 283-291 mm and a depth of 36-40 mm • One side of the drum is removable. • Inner radius of 75.5 mm to 85.5 mm • Outer diameter of the central ring is 24.5 mm to 25.5 mm. • Rotates at 25 ± 1 rpm. • It should be ensured that with every turn of the drum the tablets roll or slide and fall onto the drum wall or onto each other.
37. 37. Method • For tablets with an average weight of 0.65 g or less take a sample of whole tablets corresponding to about 6.5 g and for tablets with an average weight of more than 0.65 g take a sample of 10 whole tablets. • Place the tablets in the drum and rotate it 100 times. • Remove the tablets and weigh them accurately. • The test is run only once unless the results are difficult to interpret or if the weight loss is greater than the targeted value, in which case, the test is repeated twice and the mean of the three tests is determined. • A maximum loss of weight (from a single test or from the mean of the three tests) not greater than 1.0 per cent is acceptable for most tablets. • If obviously cracked, chipped or broken tablets are present in the sample after tumbling, the sample fails the test. • If the size or shape of the tablet causes irregular tumbling, adjust the drum base so that it forms an angle of about 10º with the horizontal and the tablets do not bind together when lying next to each other, which prevents them from falling freely.