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• Quality control tests


  Tests and analysis performed to elucidate conformance to set standards and specifications
• Dosage forms requiring quality control tests

  • Solid
  • Semi-solid
  • Liquid
  • Parenteral

  
• Quality Assurance


  • Correctly implemented system incorporating Good Manufacturing Practice and Quality Control
• FPQC for Tablets


  1. Identification tests

  2. Assay

  3. Friability

  4. Disintegration test

  5. Dissolution test

  6. Uniformity of Dosage Forms

  
• Friability


  Percentage lost by tablet in packaging and transport
• Friability test


  1. Equipment: Roche Friabilator, Vanderkaamp Friabilator

  2. Setting: 25 rpm

  3. Time: 4 minutes (100 revolutions)

  4. Sample: 650 mg or greater - 6-6.5g dedusted sample, < 650 mg - 20 tablets
• Friability formula


  Friable = [(Initial weight - Final weight)/Initial weight] x 100
• Friability acceptance criteria


  • Stage 1 (10/20): NMT 1%
  • Stage 2 (20/40): NMT 1% (average of 3 trials)
  • If new formulation: NMT 0.8%
• There should be no capping and chipping
• Disintegration test


  1. Equipment: Basket rack assembly

  2. Requirements: 6 cylindrical tubes, 10 mesh wire cloth at bottom portion and disks

  3. Temp: 37 ± 2°C; 29-32 cycles/min

  4. Goal: Impalpable core
• Disintegration acceptance criteria


  • Not more than 2 of the 18 samples tested failed to disintegrate
• Dissolution test


  1. Apparatus: Vessel size, medium, temperature

  2. Q = % Labeled Claim - Drug Released x 100

  3. Acceptance Criteria: 30 mins, 1hr, 4 hours

  
• Dissolution acceptance criteria


  • Each unit is not less than Q+5%
  • Average of 12 units is equal to or greater than Q
  • Average of 24 units is equal to or greater than Q, no more than 2 units are less than Q-15%, no unit is less than Q-25%
• Uniformity of Dosage Forms

  Ensures that each tablet will meet specification for potency
• Weight Variation


  1. For tablets with active ingredient as major portion, control of weight may be presumed to be an adequate control of drug content uniformity

  2. Acceptance Criteria: No more than 2 tablets are outside the % acceptable weight variation, no unit is outside twice the % acceptable variation

  
• Content Uniformity


  1. For tablets with ≤25 mg API per dose comprising 25% or less by weight of the dosage unit

  2. 10 dosage units are assayed individually and requirements for content uniformity are met if amount of active ingredient in each unit lies within the range of 85%-115% of Label claim, with SD <5%

  3. New Acceptance Criteria: Acceptance Value (AV) calculated must be less than or equal to L1 (15) for the first 10 units tested, if not met, retest 20 more units and the AV calculated must be equal to L1 for 30 units

  
• FPQC for Capsules


  • Identification tests
  • Assay
  • Disintegration
  • Dissolution
  • Uniformity of Dosage Forms

  
• FPQC for Semi-Solid Dosage Forms

  • Identification tests
  • Assay
  • pH
  • Spreadability
  • Spatula Feel
  • Melting Range

  
• Procedure for Non-Aerosol Containers

  1. Remove labelling, clean and dry containers

  2. Weigh individually

  3. Remove contents from each container and dry

  4. Weigh each empty container

  5. Compute for the net content and % Labeled Content
• Acceptance Criteria for Non-Aerosol Containers

  • %LC of any single container is NLT 90% where the labeled amount is ≤60 g or 60ml
  • %LC of any single container is NLT 95% where the labeled amount is >60 g or 60ml but NMT 150g or 150ml

  
• Procedure for Aerosol Containers

  1. Remove labelling, clean and dry containers

  2. Weigh individually

  3. Remove contents from each container by employing safe technique

  4. Remove any residual contents with suitable solvents, then rinse with few portions of methanol

  5. Retain as a unit the container, the valve, and all associated parts, and heat them at 100°C for 5 minutes

  6. Cool and weigh empty container

  7. Compute for the Net content and %LC
• Acceptance Criteria for Aerosol Containers: Net content is NLT labeled amount
• Procedure for Metal Particles in Ophthalmic Ointments

  1. Extrude all the contents in a Petri dish

  2. Heat at 85°C for 2 hours and cool

  3. Invert Petri dish on the stage microscope

  4. Examine the Petri dish for metal particles

  5. Count the number of metal particles that are ≥50μm or larger in any dimensions
• Acceptance Criteria for Metal Particles in Ophthalmic Ointments


  • The total number of such particles in all 10 tubes does not exceed 50, and if not more than 1 tube is found to contain more than 8 of such particles
• Microbial Content Tests


  • Total Aerobic Count: Tryptone Soy Agar, Incubation: 30-35°C for 2-3 days
  • Total Yeast and Molds: Potato Dextrose Agar, Incubation: 20-25°C for 5-7 days
• FPQC for Liquid Dosage Forms


  • Identification tests
  • Assay
  • pH
  • Appearance - color, odor taste
  • Deliverable volume

  
• Procedure for Deliverable Volume Test

  1. Gently pour the contents of each container into separate dry graduated cylinders of a rated capacity not exceeding two 1/2 times the volume to be measured, and calibrated to contain

  2. Allow each container to drain for a period not to exceed 30 minutes for Multi-unit containers and 5 seconds for Single-unit containers
• FPQC for Suspensions


  • Sedimentation volume
  • Degree of Flocculation
• Sedimentation Volume (SV)


  SV = settled volume / total or initial volume of suspension

  IDEAL SV = 1
• FPQC for Emulsions


  • Test for Type of Emulsion
  • Test for Creaming, Cracking, Breaking, phase Separation, and phase Inversion
  • Gravitational and Temperature Stress test (50°C-70°C)
• These tests are applicable to products labeled to contain NMT 250mL, whether supplied as liquid preparations, or liquid preparations that are constituted from solids upon the addition of a designated volume of a specific diluent

  
• Sample Size


  10 containers initially; 20 containers on retest
• Procedure


  1. Gently pour the contents of each container into separate dry graduated cylinders of a rated capacity not exceeding two 1/2 times the volume to be measured, and calibrated to contain. Avoid the formation of bubbles in doing this.

  2. Allow each container to drain for a period not to exceed 30 minutes for Multi-unit containers, and 5 seconds for Single-unit containers.
• Sedimentation volume (SV)


  Settled volume / total or initial volume of suspension
• Degree of Flocculation (p)

  (ultimate sedimentation volume of flocculated suspension (Vu)/ultimate sedimentation volume of deflocculated suspension)
• Ease of Redispersibility


  100% redispersable with minimum agitation
• Particle Size Determination


  • Optical Microscopy
  • Sedimentation Rate
• Viscosity


  Should pour readily and evenly from its container
• Zeta Potential Determination


  Repulsive forces between particles
• Leaker's Test


  Uses negative pressure within an incompletely sealed ampule while ampules are in a deeply colored dye solution of 1% methylene blue solution