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Quality Control Tests for Tablets, Capsules, Powders, Creams, Ointments

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  1. 1. Presented By Y.Divya M.Pharmacy Ist Year I sem Pharmaceutical analysis SPMVV
  2. 2. o Introduction to Quality control oTypes Of Solid & Semi Solid Dosage Forms oQuality Control Tests For Capsules oQuality Control Tests For Powders oQuality Control Tests For Creams And Ointments oConclusion oReferences
  3. 3. Quality control: It is a small part of QA that is concerned with sampling, testing and documentation during manufacturing and also after completion of manufacturing. Definition: In general terms, Quality control refers to a set of steps taken during manufacturing of a product to ensure that it meets the requirements and that the product is reproducible.
  4. 4. Quality Control Tests For Capsules oSolid unit dosage forms oMedicinal agents and/or inert substances are enclosed in a small shell of gelatin oGelatin capsule shells may be hard or soft, depending upon their composition.
  5. 5. The Quality control tests to be performed for Capsules are: Quality Control Test Uniformity of mass Uniformity of contents Content of active ingredients Uniformity Of weight Dissolution Disintegration
  6. 6. 1.Uniformity Of Weight: Weigh Intact Capsule Open the capsule and Remove the contents without losing any part of shell For soft capsules, contents are removed by washing shell with ether or suitable solvent Now weigh empty shell. Difference in weights gives Weight of contents Repeat procedure with 19 capsules. Determine average weight
  7. 7. 2.CONTENT OF ACTIVE INGREDIENT The amount of active ingredient is determined by the method described in Assay 3. UNIFORMITY OF CONTENT •Applicable to capsules that contain less than 10mg or less than 10 % w/w of active ingredient. •For capsules containing more than one active ingredient, the test has to be carried out for each active ingredient. •This test should be carried out only within the accepted limits of the stated amount. •The content of active ingredient is determined by taking each of 10 capsules randomly using method given in monograph or by any other suitable analytical method of equivalent accuracy and precision.
  8. 8. 4.UNIFORMITY OF MASS Weigh Intact Capsule Open the capsule Remove the contents without losing any part of shell Difference in weights gives Weight of contents Now weigh empty shell For soft capsules, contents are removed by washing shell with ether or suitable solvent Repeat procedure with 19 capsules Determine average weight
  9. 9. 5.DISINTEGRATION TEST: Repeat the test omitting the disc preparation complies with the test if all the capsules tested disintegrate NLT 16 of the total of 18 capsules tested disintegrated If the capsules adhere to the disc or Fail to comply test Assembly was removed from liquid Pass the test if all of them are disintegrated 1 or 2 capsules fail to disintegrate, repeat the test with 12 additional capsules Introduce one capsule into each tube and, add a disc if indicated. Suspended it in beaker containing specified liquid operate the apparatus for the specified time.
  10. 10. Draw samples & perform analysis as directed in monograph Lower the basket & Operate Paddle: Allow capsule to sink to bottom of vessel Basket: Place in dry basket at beginning of test Place one capsule in apparatus Assemble & warm to 36.5oC to 37.5oC Place stated volume of dissolution medium in apparatus 6.DISSOLUTION TEST
  11. 11. Tests IP BP USP Uniformity of weight 90-110% NS NS Content of active ingredient NS <10% NS Uniformity of content 85-115% 85-115% 85-115% Uniformity of mass <10% <10% <10% Disintegration test Hard capsules <30min <30min <30min Soft capsules <60min <60min <60min Enteric capsules 3hrs NS NS Gastro-resistant 3hrs NS NS Quality Control Parameters For Capsules As per IP, BP USP
  12. 12. Quality Control Tests For Powders Powders are subdivided solids which are classified according to the size of their constituent particles which range from <1.25 micrometer to 1.7mm Classification Of Powders: 1.Bulk powders 2.Divided powders 3.Dusting powders 4.Insufflations
  13. 13. Quality Control Tests To Be Performed Are: •Particle size analysis •Angle of repose •Bulk density •Tapped density •Hausner’s ratio •Flowability
  14. 14. 1.Particle Size Analysis: The powders have been classified into: As per vegetable & Animal origin: Very Coarse(#8): All particles pass through sieve no.8 and not more than 20% through sieve no.20 Coarse (#20): all particles pass through sieve no.20 not more than 40% through sieve no.60 Moderate(#40): All particles pass through sieve no.40 and not more than 40% through sieve no.60 Fine(#60): All particles pass sieve no.60 and not more than 40% through sieve no.80 Very Fine: All particles pass through this sieve. There is no limits as to greater fineness.
  15. 15. Powders of chemical drugs are classified as: Coarse (#20): All particles pass through sieve no.20 not more than 40% through sieve no.60 Moderate(#40): All particles pass through sieve no.40 and not more than 40% through sieve no.80 Fine(#60): All particles pass sieve no.60 and not more than 40% through sieve no.80
  16. 16. 2.Powder Flowability: Powder flowability is the ability of powder to flow in a desired manner in a specific piece of equipment. Flow of powders may be: •Free flowing •Non-flowing or cohesive. Flow Patterns: •Funnel Flow •Mass Flow
  17. 17. Measurement of Flow properties: Flow Properties of Powder Penetometry Powder Rheometer Cohesive index Shear cell method Flow through Orifice Carr’s Index & Hausner’s ratio Angle Of Repose
  18. 18. Angle of Repose: The internal angle between the surface of the pile and height of the pile. It depends upon: •Density •Surface area •Shape of the particles •The coefficient of friction of material Flow Property Angle of Repose (degrees) Excellent 25–30 Good 31–35 Fair—aid not needed 36–40 Passable—may hang up 41–45 Poor—must agitate, vibrate 46–55 Very poor 56–65 Very, very poor >66
  19. 19. Carr’s Index & Hausner’s Ratio: Both are determined by measuring bulk volume and tapped volume of powder Compressibility Index (%) Flow Character Hausner Ratio 10 Excellent 1.00–1.11 11–15 Good 1.12–1.18 16–20 Fair 1.19–1.25 21–25 Passable 1.26–1.34 26–31 Poor 1.35–1.45 32–37 Very poor 1.46–1.59 >38 Very, very poor >1.60
  20. 20. Flow Through An Orifice: •Useful only for free flowing powders. Types Of flow Rate: •Mass flow rate: Quantity of powder flow per minute. •Volume flow rate: Time taken by the powder in a container to drain out.
  21. 21. Shear Cell Method: In the shear cell method, the force necessary to shear the powder bed by moving the upper ring is determined. Flow Factor Index Flowability ff < 1 Non flowing 1 < ff < 2 Very Cohesive 2 < ff < 4 Cohesive 4 < ff < 10 Easy flowing Ff > 10 Free Flowing
  22. 22. COHESION INDEX: Determined by integrating the negative areas under force displacement curve. A low cohesion index is associated with non-cohesive free flowing powders
  23. 23. FT4 POWDER RHEOMETER: The forces causing deformation of powders is measured here. This gives measurement of: •Flow energy •Shear properties •Bulk properties Downward Test Mode: Used to measure Basic Energy Flow(BEF)
  24. 24. Upward Test Mode: Used to measure the Specific Energy(SE) which is flow energy per gram of powder tested.
  25. 25. PENETROMETRY: The pressure of penetration in pascal was used to estimate flow rate. Particle size should be in the range of: 0.250-0.630 mm Especially used for non-consolidated pharmaceutical powder excipients: •Sodium chloride •Sodium citrate •Boric acid •Sorbitol
  26. 26. Quality Control Tests For Semisolid Dosage Forms Semisolid dosage forms are products of semisolid consistency and applied to skin or mucous membrane for therapeutic or protective action or cosmetic function Types: Ointments Creams Gels Pastes Poultices Semisolid foams
  27. 27. Quality Control Tests For Creams & Ointments Universal Tests Description Identification Assay Impurities Specific Tests PH Apparent Viscosity uniformity Of Dosage Unit Water Content Microbial Limit Preservative Effect Particle Size Special Tests Phase Separation Uniformity in Container In vitro Release Studies
  28. 28. 1.Universal Tests: Description: This includes visual examination to identify changes in color, separation, crystallization etc., in the final appearance of the product. The description should specify the content or label claim of the product. 2.Identification: Quantitative identification of active ingredients in the finished dosage form. Methods: •IR •Raman spectroscopy •Chromatography
  29. 29. 3.ASSAY: The quantity of drug present in unit weight or volume of ointment or cream is determined by: •Spectrophotometric method •Titrimetric method •Chromatographic method •Microbial assays Detected by UV By using RP-Columns Chromatographic separation Formulation matrix Extract drug with solvents
  30. 30. 4.MICROBIALASSAYS Microbial assays are recommended for preparations containing antibiotics such as: •Amphotericin-B •Bacitracin •Chlortetracycline HCl •Gentamycin sulphate Method: •Cylindrical plate or plate assays •Turbidimetric or tube assays 5.IMPURITIES: The impurities arising from degradation of drug substance and during the manufacturing process of drug product should be assessed and controlled
  31. 31. II.SPECIFIC TESTS: 1.PH •Creams and ointments contain very limited quantities of water or aqueous phase, •Hence this test is not always warranted. •Formulation dependent. •Not included in compendia drug product monograph. 2.APPARENT VISCOSITY: •Formulation and/or process dependent. •Not included in compendia drug product monograph.
  32. 32. 3.UNIFORMITY OF DOSAGE UNIT: This test is applicable for dosage forms packaged in single unit containers. 4.Water Content: Determined by Titrimetric methods. Reagent: KF reagent Preparations Max., allowable Limit of water Ointments 0.5 to 1.0% Bacitracin, Nystatin, Chlortetracycline HCl ointment NMT 0.5% Amphotericin-B, Gentamycin sulphate, Neomycin sulphate, Erythromycin sulphate, Tetracycline HCl Upto 1%
  33. 33. 5.ANTIMICROBIAL PRESERVATIVE EFFECT: Method: Pour plate technique Solns of different samples Mixed with Tryptone Azolectin(TAT) broth separately Add all cultures into each mixture Incubate & count no. of organisms on 7,14, 21, 28 days of incubation
  34. 34. On 14thday No.of vegetative cells NMT 0.1% of intial conc On 28th day No, of organisms should be below or equal to intial conc 6.PARTICLE SIZE DETERMINATION: •Dilute preparation with equal volume of glycerol/ liquid paraffin as per monograph. •Mount on glass slide. •Observe through microscope. •Calculate the no. of particles having max., diameter within stated limit.
  35. 35. III.SPECIFIC TESTS FOR SEMISOLID DOSAGE FORMS: 1.PHASE SEPARATION TEST: •Visual tests. •Done by measuring the volume of separated phases. 2.UNIFORMITY IN CONTAINERS: Type Assay Limit Multiple dose products containing >5gm 90-110% of product label Multiple dose products containing <5gm 90-110% of product label
  36. 36. Procedure: •Expose the product in tube. •Visually inspect product. •Remove a sample of product from top, middle and bottom portions of the tube. •Perform assay separately Products Packaged In Containers Other Than Tubes: •Select a syringe such that it reaches bottom of the container. •Remove plunger & cut of bottom of syringe barrel. •Sample from one side of container is slowly withdrawn by slowly inserting syringe barrel into container until it reaches bottom.
  37. 37. •Twist syringe barrel containing sample core and remove barrel. •Insert the syringe plunger and carefully extrude the equal portions representing Top, middle, bottom of container. •Perform assay separately for each portions
  38. 38. INVITRO DRUG RELEASE STUDIES: These studies are conducted in order to ascertain the release of drug from the formulation matrix. Apparatus: Franz diffusion cell
  39. 39. Add equal vol. of fresh medium after each sampling Withdraw samples from receiver side in different time intervals Phosphate buffer PH 5.4 Receiver side is filled with known volume of release medium Heat to 0.5oC by circulating water Known qty of test product is applied uniformly over the membrane on donor side
  40. 40. CONCLUSION: From this it can be concluded that, though a no. of quality control tests have been assigned for sold & semisolid dosage forms in IP, BP, USP yet there occurs some difference between them. Hence in order to overcome that, the different tests & limits specified in different pharmacopoeias have to be streamlined and harmonized in such a way that, tests meets specified limit as per harmonized one and later meets regulatory requirements of that particular country.
  41. 41. REFERENCES: 1.The controller of publication . Indian pharmacopoeia 5th edition. New Delhi Ministry of health and family welfare. Indian; 2007 volume I. 2.Published on behalf of medicines and Health Care Products Regulatory Agency; The department of Health, Social servicesand public safety, British Pharmacopoeia 6th edition. Great Britain; 2010. Volume II. 3.United States Pharmacopoeia 29 National Formulary 24(united States Pharmacopoeia 29-NF) supplement I, is current from April 1, 2006 through July 31,2006. 4.Prescott, J.K., and Barnum R.A., On Powder Flowability, Pharmaceutical Technology, October 2000, PP. 60-84 and 236. 5.Baxter, Thomas J., “When Powders Flow Like Water”:Addressing two phase flow effects in tablet press feed system,” Tablets & Capsules, march 2009, volume 7. No: PP 26-32.