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Finished products · Tablets (immediate release)

Dissolution of Immediate-Release Tablets (Paracetamol 500 mg example)

Measures the percentage of paracetamol released from each of six tablets after 30 minutes in 900 mL of phosphate buffer at 37 °C, stirred by a paddle at 50 rpm, and judges the batch against the Q value using the staged acceptance criteria.

  • Dissolution (apparatus 2, paddle) with UV-Vis spectrophotometry
  • Dissolution tester
  • UV-Vis
  • Analytical balance

Reference: Typical conditions based on pharmacopoeial approaches for paracetamol / acetaminophen tablets. Always follow your approved specification and STP.

PRINCIPLE

Why this method works

Each tablet is placed in a vessel of buffer at body temperature under gentle, standardised agitation. After the stated time, a filtered sample of the medium is diluted and its UV absorbance near 243 nm is compared with that of a paracetamol reference standard of known concentration. Because the medium volume is known, the absorbance ratio gives the amount dissolved, which is expressed as a percentage of the label claim.

Instruments used

MATERIALS

Reagents & standards

ReagentGrade / specification
Dissolution mediumPhosphate buffer pH 5.8 (or pH 6.8 if your monograph states), prepared from potassium dihydrogen phosphate and sodium hydroxide as per the pharmacopoeial buffer recipe
Paracetamol reference standardCertified purity (pharmacopoeial RS or a qualified working standard)
WaterPurified water
FiltersValidated syringe filters (e.g. 0.45 µm) or cannula filters, shown not to adsorb paracetamol
SAMPLE PREPARATION

Preparing the sample

  1. 01

    Prepare medium

    Prepare 6 × 900 mL buffer, check pH and deaerate.

  2. 02

    Equilibrate

    Fill vessels and bring to 37 ± 0.5 °C with paddles at 25 mm.

  3. 03

    Add tablets

    Drop one tablet into each vessel and start at 50 rpm.

  4. 04

    Sample at 30 min

    Withdraw about 10 mL from the sampling zone and filter.

  5. 05

    Dilute

    Dilute 1.0 mL of filtrate to 100 mL with medium.

  6. 06

    Measure

    Read absorbance at about 243 nm against medium as blank.

Procedure

  1. 1Prepare the buffer, check that pH is within the stated range, and deaerate it.
  2. 2Place 900 mL of medium in each of six vessels and allow it to reach 37 ± 0.5 °C. Confirm the temperature in each vessel.
  3. 3Set the paddles at 25 ± 2 mm above the vessel bottom and the speed to 50 rpm.
  4. 4Weigh each tablet if the procedure asks, then drop one tablet into each vessel, starting the timer with the first tablet and staggering the others if needed.
  5. 5At 30 minutes withdraw about 10 mL from the zone midway between the paddle top and the medium surface, at least 1 cm from the wall.
  6. 6Filter immediately, discarding the first few mL of filtrate as established in validation.
  7. 7Pipette 1.0 mL of the filtrate into a 100 mL volumetric flask and make up to volume with medium (about 5.5 µg/mL at 100% release).
  8. 8Measure the absorbance of each sample at the maximum near 243 nm in a 1 cm cell, using medium as the blank.

Standard preparation

  1. 1Accurately weigh about 50 mg of paracetamol reference standard into a 100 mL volumetric flask.
  2. 2Dissolve in medium (a small amount of methanol may be used first if your method allows) and make up to volume with medium.
  3. 3Pipette 1.0 mL into a 100 mL volumetric flask and make up to volume with medium (about 5 µg/mL).
  4. 4Measure the standard in replicate (e.g. five readings) to confirm precision.

Notes for analysts

  • Do not change the apparatus, speed, medium or Q on your own: these are fixed by the specification.
  • Note any coning, floating or sticking in the raw data; it may explain unexpected results.
  • If the medium is not deaerated, document the validation that showed deaeration is not needed.
  • HPLC can be used instead of UV when excipients or other actives interfere at the measuring wavelength.
  • When samples are withdrawn at several time points without replacing medium, correct the calculation for the volume removed.
TEST CONDITIONS

Method parameters (typical)

ApparatusUSP apparatus 2 (paddle); some monographs use apparatus 1 (basket) at 100 rpm
MediumPhosphate buffer pH 5.8 (or pH 6.8), deaerated
Volume900 mL
Temperature37 ± 0.5 °C
Rotation speed50 rpm
Time30 minutes
Sample volumeAbout 10 mL, filtered
MeasurementUV absorbance at about 243 nm, 1 cm cell, medium as blank
Tolerance (Q)Typically not less than 80% (Q) of the labelled amount dissolved in 30 minutes
BEFORE YOU REPORT

System suitability & sequence

ParameterLimit
Apparatus statusMechanical calibration, speed, temperature (and PVT if required) within due date
Standard absorbance %RSDTypically not more than 2.0% for replicate readings
Standard absorbance rangeWithin the validated linear range of the spectrophotometer (commonly 0.2–0.8 AU)
Medium temperature37 ± 0.5 °C at start and end of the test

Typical sequence

  1. 1Blank (medium)
  2. 2Standard × 5 (precision check)
  3. 3Samples from vessels 1–6
  4. 4Standard check at end
CALCULATION

Calculation with a worked example

% dissolved = (AT ÷ AS) × CS × D × V ÷ LC × 100

Where

AT
Absorbance of the sample solution
AS
Mean absorbance of the standard solution
CS
Concentration of paracetamol in the standard solution, corrected for purity (mg/mL)
D
Dilution factor of the sample (here 100)
V
Volume of medium in the vessel (mL)
LC
Label claim (mg per tablet)

Given

AT (vessel 1)
0.352
AS (mean of 5)
0.3584
Standard weight
50.2 mg in 100 mL, then 1 → 100 mL
Standard purity
99.8%
CS
50.2 ÷ 100 ÷ 100 × 0.998 = 0.005010 mg/mL
D
100
V
900 mL
LC
500 mg

Working

  1. AT ÷ AS = 0.352 ÷ 0.3584 = 0.9821
  2. Concentration in diluted sample = 0.9821 × 0.005010 = 0.004920 mg/mL
  3. Concentration in vessel = 0.004920 × 100 = 0.4920 mg/mL
  4. Amount dissolved = 0.4920 × 900 = 442.8 mg
  5. % dissolved = 442.8 ÷ 500 × 100 = 88.6%
  6. All six vessels: 88.6, 90.8, 87.3, 92.1, 89.6, 90.1% (mean 89.7%)
  7. S1 criterion: each unit not less than Q + 5% = 85%. Lowest is 87.3%, so the batch passes at S1.

Vessel 1 = 88.6% dissolved in 30 minutes; all six units ≥ 85% (Q + 5%), so the batch passes at stage S1.

ACCEPTANCE CRITERIA

What result passes

  • Stage S1 (6 units): each unit not less than Q + 5%.
  • Stage S2 (6 more units, 12 in total): average of 12 units not less than Q, and no unit less than Q − 15%.
  • Stage S3 (12 more units, 24 in total): average of 24 units not less than Q, not more than 2 units less than Q − 15%, and no unit less than Q − 25%.
  • For paracetamol tablets Q is typically 80% at 30 minutes; use the Q and time in your approved specification.
METHOD VALIDATION

Validation parameters (ICH Q2(R2))

ParameterTypical requirement
SpecificityNo interference from placebo, medium or filter at the measuring wavelength
LinearityTypically from about 10% to 120% of the expected concentration, r ≥ 0.999
Accuracy (recovery)Drug spiked into placebo in medium recovered within about 95–105%
PrecisionRepeatability and intermediate precision across analysts, days and apparatus
Filter validationFiltered versus centrifuged (or unfiltered standard) results agree, typically within 2%
Solution stabilitySamples and standards stable for the analysis period at room temperature
Discriminating powerMethod detects meaningful formulation or process changes (shown during development)
In LimsPulse · Sample Management

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