DDS LEC - Solid Dosage Forms: Tablets Part II

Quality Standards & Compendial Requirements

• Tests performed in intermediate and finished products before and after the manufacturing process in order to comply with the specifications

• Routinely run to monitor the process from powder to granules up to its compression

  • Monitored every step so if there’s a problem in terms of the granulation, it can be addressed immediately

• Also performed during product development

  • Used for Process Validation

Compendial Standards

Pharmaceutical standards in a compendium

Process Validation

A small-scale test run of the procedures and processes, making sure that before the upscale or the manufacturing scale production, the process meets the specifications

In Process Quality Control Tests ((IPQC Tests)

Tests done for intermediate testing

Finished Product Quality Control Tests (FPQC Tests)

Tests done for finished product testing

Particle Size Distribution

• Can also be called Grain-size Distribution

  • Represents the relative proportions of different particle or grain sizes in a sample

• Can be performed using a sieve with various sieve numbers, microscope methods, or using a RO-TAP Mechanical Sieve Shaker

Ideal Tablet

Composed of:

• 80% Good

• 20% Fine Granules

Bulk Density

• Ratio of the mass to the volume of the untapped powder sample

• It describes the packing of particles or granules

  • Dictates how much space is needed for the powder or granules to be safely stored

Tapped Density

Ratio of the mass of the powder to the volume occupied after it has been tapped for a definite number

Method I

• Commonly used method

• Method using Graduated cylinder in Bulk and Tap Density Tester

Method II

Method using Volumeter

Method III

Method using Vessel

Moisture Content

• Presence of water in a product

• 2-3% moisture content before starting compression when the tablet undergoes wet granulation

• Directly measure the moisture content of a sample by using the Loss On Drying (LOD) technique

  • If there is excessive moisture, granules will stick to the dye cavity

  • Will not result in a 1 solid tablet because of sticking

• If done manually, done in a drying oven with a balance to determine the initial and final weight of the sample and using a simple mathematical calculation to determine the moisture content

Tablet Hardness

• Determines the quality of tablet in terms of rigidity and resistance to chipping or breakage during transport and storage

• Stokes-Monsanto Tablet Hardness Tester

  • If not available, use Rule of Thumb

Stokes-Monsanto Tablet Hardness Tester

Spring gauge and screw mechanism

1. Place the tablet upright

2. Screw clockwise

3. Continue screwing until a crack forms

4. Not the reading - Tablet Hardness

Uncoated, Oral Tablet Acceptable Hardness Range

4-10 kg

Sublingual, Chewable Acceptable Hardness Range

2-3 kg

Buccal Tablets Acceptable Hardness Range

10 kg

Sustained Release Acceptable Hardness Range

10-20 kg

Rule of Thumb

Used if Stokes-Monsanto Tablet Hardness Tester is not available

1. Place the tablet in between the 2nd and 3rd finger

2. Let it fall to the floor and the tablet should not break

Tablet Weight

• Establish how many granules are placed in the die cavity and it should be uniform

• Quantity of fill in the die of the tablet press

• USP Weight Variation Test - determination of dosage form uniformity

  • Minimum of 10 tabs are weighed individually, and the average is calculated

  • The tablets are assayed to determine homogeneity of drug distribution

Maximum % Weight Variation Allowed for <130 mg

± 10%

Maximum % Weight Variation Allowed for 130 mg to 324 mg

± 7.5%

Maximum % Weight Variation Allowed for >324 mg

± 5%

Tablet Thickness

• Non-official test for tablets

• In-house specification sample (within the manufacturing company): ± 5%

• Can give an idea in terms of the disintegration and dissolution profile

Tablet Friability Test

Tests the durability of tablets during packaging processes

• Makes use of a tumbling apparatus where tablets are exposed to rolling and repeated shocks from free fall within the transparent synthetic polymer with polished internal surface drum

• Condition: 100 revolutions

• Speed: 25 ± 1 revolution per minute (4 minutes)

• Criteria: Weight loss should not be more than 1%

• Rotates clockwise and drops the tablets and will continuously repeat

Twice

In case of cracked, cleaved, or broken tablets present, repeat the test _____.

% Weight Loss Formula

Disintegration Test

Measures the ability of a tablet to break apart into smaller particles or granules to allow the active drug to be absorbed into the body

• 1 tab is placed per cylinder, then a disk is placed in top of the tablet to prevent the tablet from floating

• Condition:

  • Volume: 900 mL distilled water (or whatever is specified)

  • Temperature: 37 ± 2°C - body temp

  • Sample: 6 tablets

  • Time:

    • Uncoated or Plain Tablets: 30 mins

    • Delayed-Release Tablets: 60 mins

• Criteria:

  • All tablets should have disintegrated completely

  • If 1 or 2 tablets fail, repeat the test on 12 additional tablets (repeat test twice)

Time for Uncoated or Plain Tablets in Disintegration Test

30 minutes

Time for Delayed-Release Tablets in Disintegration Test

60 minutes

Dissolution Test

• Process by which solid substances enters in a solvent to yield a solution

• From powders, after disintegration, the drug is slowly dissolved or when it is present in the solution, it can be concluded that it is now ready for absorption

• Type of Apparatus:

  • Apparatus I - Rotating Basket

  • Apparatus II - Rotating Paddle

  • Apparatus III - Reciprocating Cylinder

  • Apparatus IV - Flow-Through Cell

  • Apparatus V - Paddle Over Disk

  • Apparatus VI - Rotating Cylinder

  • Apparatus VII - Reciprocating Holder

• Importance:

  • Guides formulation and product development

  • Product monitoring

  • Ensures consistent bioequivalence characteristics from batch to batch

In-Vitro

Establishes the amount of drug released

In-Vivo

Establishes the amount of drug absorbed

Quadrant 1

• High Solubility

• High Permeability

Fast to dissolve, Fast to be absorbed by the body for its therapeutic effect

Quadrant 2

• Low Solubility

• High Permeability

Slow to dissolve, Fast to be absorbed by the body for its therapeutic effect

Quadrant 3

• High Solubility

• Low Permeability

Fast to dissolve, Slow to be absorbed by the body for its therapeutic effect

Quadrant 4

• Low Solubility

• Low Permeability

Show to dissolve, Slow to be absorbed by the body for its therapeutic effect