2-230214201459-9c2f9030nutritionand health.pptx

Jutrition and health

1. QUALITY CONTROL OF SOLID DOSAGE FORMS

2. TABLETS Tablets are solid dosage forms containing one or more active ingredients. Unit-dose dosage forms. Obtained by single or multiple compression. May be uncoated or coated. They are usually intended for oral administration.

3. QC TESTS OF TABLETS Classified into 2 groups: Physical tests Chemical tests Weight variation Hardness Thickness & diameter Friability Disintegration time Assay Content uniformity Dissolution

4. Weight variation Actual weight of tablet; determined by diameter of die & weight adjustment knob on machine. Known as – compression weight. Weight control – routinely adjusted to ensure that specified wt; is reproduced.

5. Cont... Limits for uncoated tablets (USP): For 20 tablets Average tablet weight Percentage deviation allowed 18 tablets 2 tablets 130 mg or less ±10% ±20% 130 to 324 mg ± 7.5% ±15% More than 324 ± 5% ±10%

6. Procedure Weigh 20 tablets as a whole. Divide total weight by 20 – average wt. Weigh 20 tabs – individually. Calculate the result.

7. Hardness Important test – related to solubility. Mechanical hardness testers used commonly are: Strong-Cobb Stokes monsanto Eureka Pfizer Measures resistance to crushing of tablet. Average hardness limit = 5-10 kg/cm 2 German made instruments – scale in Newton (1N=9.8kg)

8. Manual Strong-Cobb type Stokes monsanto type Pfizer type DIFFERENT HARDNESS TESTERS

9. Procedure Eureka instrument – breaking force applied by a beam fastened to one end to a pivot. Motor moves beam at constant speed. Increases force against tablet, on which other end of beam rests. When tablet breaks – a micro-switch is activated, that stops motor. Indicator shows the breaking strength on scale in kgs .

10. Cont... Proper hardness for tablets ensures that the tablet withstand the shock of: handling, packing & shipping.

11. Thickness & Diameter Measured by vernier callipers. Initially an in-process control during production . Thickness – directly related to hardness. Limits for tablet thickness – depends on tablet weight. Purpose – trouble free packing .

12. Cont... Thickness range = 2-4 mm (depending on diameter of tablet). Diameter range = 4-13 mm. Apply on tablets which are not sugar coated, enteric or film coated. Deviation allowed = ±5% of stated diameter. For diameter exceeding 12.5 mm = ±3% deviation.

13. Friability Due to friction & shock – tablets chip, cap or break. So equipment Roche friabilator developed. Cause self abrasion of tablets; as cylinder section rotates. Tablets undergo shock – as they fall 6 inches on each turn. Operation time = 4 minute or 100 revolutions. i.e., 25 rev/min.

14. Friabilators

15. Cont... Tablets weighed & compared to their original weight. Loss due to friction or abrasion – measure of friability. Value – expressed in % w/w. Limits of wt; loss < 0.8 %. If capping or breaking – friability values not calculated. Tablet more friable – when lose moisture.

16. Disintegration Limits of DT = 5-30 min in different pharmacopoeias. Attempts to simulate in-vivo conditions. Test – doesn’t correlate with physiological conditions. Test – cause breakdown/disintegration of tablet. Test doesn’t cause complete solution of tablet.

17. Cont... Complete disintegration – a state in which any residue of tablet remaining on screen of apparatus is a soft mass having no firm core . Except fragments of insoluble coating. USP disintegration test – specific apparatus & method. describes test procedure for each type of tablet.

18. Cont... Disintegration time – given in individual monographs & tested for compliance. Except for tablets – troches, chewable, sustained release. So according to type of tablet – procedure is applied on 6 or more tablets.

19. Apparatus Consists of: Basket-rack assembly – holds the tablets. Suitable vessel – for immersion fluid (1L beaker) Thermostatic arrangement – heating fluid between 35 & 39 °C . Device – for raising and lowering basket in immersion fluid. frequency 28 to 32 cycles/min. through a distance = 5-6 cm.

20. Disintegration test apparatus

21. Cont... Volume of fluid in vessel at; Upward stroke – wire mesh 2.5 cm below surface of fluid. Downward stroke – wire mesh 2.5 cm above bottom of vessel. Time for; upward stroke = downward stroke Change in stroke direction – smooth transition.

22. Cont... Basket-rack assembly – consists of 6 open-ended glass tubes. Each glass tube; Length = 7.75 ± 0.25 cm Internal diameter = 21.5 mm Wall thickness = 2 mm Tubes held in vertical position – by 2 plastic plates . Diameter = 9 cm Thickness = 6 mm

23. Standard Basket-Rack Assembly

24. Cont... 6 holes in each plate – 24 mm dia. Holes – equidistant from centre of plate & equally spaced. To under surface of lower plate – attached a 10-mesh stainless steel gauge. Plastic plates supported by stainless steel plates. Diameter = 9 cm Thickness = 1 mm 6 holes – 20 mm dia.

25. Cont... Central shaft – attached to stainless steel plate. Length = 8 cm Parts of apparatus – assembled & held rigidly by 3 blots. Design of apparatus – may be changed. But specs for glass tubes & mesh sizes – maintained.

26. Cont... Disks – each tube provided with perforated cylindrical disk. Purpose ; to obtain solid to solid contact as in stomach. to prevent floating tablets from coming out of tubes. due to low specific gravity or air imprisonment

27. Cont... Disk specifications: Thickness = 9.5 ± 0.15 mm Diameter = 20.7 ± 0.15 mm Made up of transparent plastic material. Sp; gravity – 1.18 to 1.120 Five 2mm holes in disks. One hole in middle. 4 parallel with it equally spaced (at 6mm radius).

28. Plastic disk

29. Cont... On sides of cylindrical disks – 4 notches equally spaced. Notches – form V-shaped planes; perpendicular to ends of disk. Notch opening on bottom of cylinder = 1.60 mm Notch openings on top = 9.5 mm All surfaces of disk – smooth.

30. Procedure Uncoated tablets: Place 1 tablet in each of six tubes. A disk to each tube is added. Operate apparatus. Water as immersion fluid – unless another specified in individual monograph. Fluid temp = 37 ± 2 °C. Time limit for operation – specified in monograph.

31. At end of time limit – lift basket from fluid. Observe tablets. All tablets – should be disintegrated completely. If 1 or 2 tablets fail to disintegrate ; repeat test on 12 additional tablets. 16 out of 18 tabs – must disintegrate completely.

32. Cont... Plain coated tablets: Place 1 tablet in each of six tubes of basket. If tablet has external soluble coating – immerse basket in water at room temp; for 5 minutes. A disk to each tube is added. Operate apparatus. Simulated gastric fluid – as immersion fluid. Fluid temp; = 37 ± 2 °C. Time limit for operation – 30 min.

33. At end of time limit – lift basket from fluid. Observe tablets. All tablets – should be disintegrated completely. If 1 or 2 tablets fail to disintegrate ; repeat test on 12 additional tablets. 16 out of 18 tabs – must disintegrate completely.

34. Cont... Enteric-coated tablets: Place 1 tablet in each of six tubes of basket. If tablet has external soluble coating – immerse basket in water at room temp; for 5 minutes. Operate apparatus without disks. Simulated gastric fluid – as immersion fluid. Fluid temp; = 37 ± 2 °C.

35. After 1 hr – lift basket & observe tabs. No disintegration, cracking or softening of tablets. Then add disk to each tube. Use simulated intestinal fluid – as immersion fluid. Operate – for 2 hrs + time limit specified in individual monograph. At end of time limit – lift basket & observe tablets. Limits – same as for uncoated tablets.

36. Cont... Buccal tablets: Apply test as for uncoated tabs –but don’t use disks. Time limit for operation – 4 hrs. Limits – same as for uncoated tabs. Sublingual tablets: Apply test as for uncoated tabs –but don’t use disks. Time limit for operation – 2 min. Limits – same as for uncoated tabs.

37. Assay 1 st step in assay – grinding of 20 tabs. Analysis of an aliquot – representing a certain amount of drug, normally in single unit. Method of analysis – prescribed in monograph. Results – as percentage of active drug in tablet. Compared with limits in monograph.

38. Content uniformity When ingredients of tablet granulation are homogenous – tablet weigh test can be considered as measure of drug content. Content uniformity test performed – when individual monograph requires. 30 tabs selected. Out of which – 10 tabs assayed individually.

39. Cont... For 10 individual tabs: All tabs = 85 to 115% of average limit in monograph. If; 9 tabs = 85 to 115% of average limit in monograph. 1 tab = 75 to 125% Then; assay remaining 20 tabs. So for total 30 tabs: 29 tabs = 85 to 115% of average limit in monograph. 1 tab = 75 to 125%

40. Dissolution Drugs having solubility – greater than 1% w/v, have no problem. But drugs having lower solubility – dissolution systems are designed. So test not used for all drugs . USP 19 – recommends dissolution for 15 dosage forms of different drugs. USP 20 – 60 drugs USP 21 (1985) – 400 drugs

41. Cont... Used to determine dissolution characteristics of solid dosage forms. Suitable dissolution characteristics – important property of drug product. Because drug absorption depends upon drug in dissolved state. Two methods used for dissolution. Method I & method II Use method – prescribed in individual monograph.

42. Method I ( apparatus 1) Rotatory basket method Apparatus – consists of following: covered vessel – made of plastic or other transparent material. motor metallic drive shaft cylindrical basket constant temp. bath

43. Dissolution apparatus

44. Cont... Vessel – immersed in suitable water bath. Water bath – maintain temperature at 37 ± 0.5°C. The vessel – cylindrical with slightly concave bottom. Height = 16 cm Internal diameter = 10 cm Capacity = 1000 ml Sides are flanged near top – to accept a fitted cover.

45. Cont... Cover has 4 ports – one of which is centred. Shaft of motor placed in centre port. One port for insertion of thermometer. 1 port – for sample removal & 1 port – for dissolution medium replacement.

46. Cont... Motor – fitted with speed regulating device. Speed limit of motor = 25 to 200 rpm Maintained – as mentioned in monograph, within ±5%. Shaft Length = 30 cm Diameter = 6mm Can be raised or lowered to position the basket. Shaft is centred – so basket rotates smoothly.

47. Cont... Basket – 2 parts. Top – attached to shaft (solid metal having 2 mm vent). Fitted to lower part by 3 clips – that allow removal of lower part. Detachable part (lower part) – made of 40 mesh stainless steel cloth (sieve opening = 420µm). Mesh is in the form of cylinder. Height = 3.66 cm Diameter= 2.5cm

48. Cont... Gold plated basket – recommended for dilute acid media. Dissolution medium – as specified in individual monograph.

49. Procedure Take 900ml dissolution medium in vessel. Vessel – already immersed in constant temp. Bath. Allow dissolution medium to – temp. 37 ± 0.5 °C. Place 1 tablet in the basket. Assemble apparatus & immerse basket in vessel. distance b/w basket & bottom of vessel = 2 ± 0.2cm. Rotate basket at rate – specified in individual monograph.

50. Cont... After time specified – withdraw samples for analysis. Analysis method – specified in individual monograph. Repeat test on 5 additional tablets. Limits If 1 or 2 tablets fail – repeat test on 6 additional tablets. 10 out of 12 tabs – must meet the requirements.

51. Method I (apparatus 2) Paddle method Apparatus – same as apparatus 1. Except: Paddle (formed from blade) – replaced with basket. Distance b/w paddle & bottom of vessel = 2.5 ± 0.2cm. Dosage unit is allowed to sink to the bottom of the vessel – before rotation of paddle. Small wire helix may be attached or placed over dosage units. in order to prevent floating.

52. Wire helix Paddle with vessel

53. Method II Distegration appartus for dissolution Apparatus – same apparatus & basket rack assembly as described under tablet disintegration test. Except: Replace 10 mesh stainless steel cloth in basket rack assembly – with 40 mesh. Also cover top of assembly with 40 mesh.

54. Cont... Adjust vessel in such a way so on downward stroke: Distance between assembly & bottom of vessel = 1± 0.1cm. Dissolution medium & procedure : as specified in monograph.

55. CAPSULES Capsules are solid dosage forms in which the medication contained within gelatine shells. Medication may be – a powder, a liquid or a semisolid mass. Usually intended to be administered orally. Two types – soft gelatine & hard gelatine capsules.

56. QC TESTS FOR CAPSULES Tests for capsules: Uniformity of weight Disintegration test Assay of active ingredients Content uniformity test (same as for tablets) Dissolution test (same as for tablets)

57. Uniformity of weight Two methods used: Method A for capsules with dry content. Method B for capsules with liquid or paste.

58. Method A Weigh a capsule. Open it – without loss of shell material. Remove contents & weigh all parts of shell. Difference between weight represent – weight of contents.

59. Cont... Perform test for total of 20 caps. Calculate the average weight. Limits for weight variation: Average capsule weight Percentage deviation allowed 18 capsules 2 capsules 120 mg or less ±10% ±20% More than 120 mg ± 7.5% ±15%

60. Method B Weigh a capsule. Open it without loss of material. Express as much contents as possible. Wash shell with ether & discard washings. Allow shell to stand – until odour of ether is no longer noticeable. Then weigh the shell.

61. Cont... Difference between weight represent – weight of contents. Perform test for total of 10 caps. Calculate the average weight. Limits for weight variation: Average capsule weight Percentage deviation allowed 9 capsules 1 capsule All weights ±7.5% ±15%

62. Assay of active ingredients 1 st step in assay – take contents of 20 capsules. Analysis of an aliquot – representing a certain amount of drug, normally in single unit. Method of analysis – prescribed in monograph. Results – as percentage of active drug in tablet. Compared with limits in monograph.

63. Disintegration test Apparatus (B.P) – consists of: Glass tube Length = 80-100 mm Internal diameter = 28 mm External diameter = 30-31mm Wire gauze (mesh 10) – fitted to lower end of tube. To form a basket. Mesh 10 = 1.70mm (pore size)

64. Cont... Glass cylinder – with flat base. Internal diameter = 45 mm Contain water – not less than 15cm deep. Water temp. = 36-38 C Basket suspended centrally in cylinder. So that can be raised & lowered repeatedly.

65. Method Place 5 capsules in basket. Basket raised & lowered at 30 times/min. Capsules disintegrated – if no particle of solid material present. Time for 5 capsules = 15 min Unless stated in individual monograph. If test fails – because of capsules aggregation Repeat on 5 caps – but individually. Longest time taken by any one capsule – disintegration time.

66. Cont... BP used above mentioned apparatus – before 1980. In 1980 – BP adopted USP disintegration apparatus. USP method: Same as for uncoated tablets. Except – upper plate of basket rack assembly, covered with removable wire cloth of mesh 10.