LimsPulse
In-process & stability · Powder blend for tablets or capsules

Blend uniformity

Checks that the active ingredient is evenly mixed through a powder blend before compression or encapsulation, by sampling the blender at about 10 locations and assaying each sample.

  • Thief sampling + HPLC / UV
  • HPLC
  • UV-Vis
  • Analytical balance
  • Sonicator
  • Centrifuge

Reference: Typical in-process test; criteria are defined in your process validation protocol and SOP.

PRINCIPLE

Why this method works

A sampling thief is pushed into the blend at defined locations and depths to remove small samples, usually 1 to 3 times the weight of one dosage unit. Each sample is assayed. The mean shows whether the right amount of drug is present, and the relative standard deviation (%RSD) shows how evenly it is distributed. A low RSD means a uniform blend.

Instruments used

MATERIALS

Reagents & standards

ReagentGrade / specification
Reference standardOf the active ingredient, certified purity
Diluent and mobile phaseAs in the product's assay method
SAMPLE PREPARATION

Preparing the sample

  1. 01

    Plan locations

    Use the protocol diagram: about 10 locations covering top, middle, bottom and dead spots.

  2. 02

    Thief sample

    Insert the thief, open, close and withdraw a unit-dose-sized sample.

  3. 03

    Transfer

    Empty each sample into a labelled container, noting location.

  4. 04

    Weigh & extract

    Weigh the whole sample (or a portion) and dissolve in diluent with sonication.

  5. 05

    Analyse

    Filter or centrifuge, dilute and assay against the standard.

Procedure

  1. 1At the end of blending, sample at the locations in the approved sampling plan, commonly 10 locations in the blender (or from the bin), including likely poor-mixing spots.
  2. 2Take each sample with a clean sampling thief, sized to about 1 to 3 times the weight of one dosage unit. Take replicate samples per location if the protocol asks.
  3. 3Transfer each sample quantitatively to a labelled volumetric flask, accurately weighing it.
  4. 4Add diluent, sonicate to dissolve the drug, cool, make up to volume and filter or centrifuge.
  5. 5Dilute to the working concentration and assay each sample by the validated method.
  6. 6Express each result as % of the theoretical (target) amount of drug in the blend.

Standard preparation

  1. 1Prepare the reference standard at the working concentration using the same diluent.

Notes for analysts

  • The chromatogram shown is illustrative only.
  • Thief sampling can disturb the blend and segregate particles, so a high result at one location may be a sampling error. Investigate before concluding the blend is not uniform.
  • Many companies support blend uniformity with stratified sampling of dosage units during compression; see your process validation approach.
  • Use the percent-RSD calculator to check the statistics.
TEST CONDITIONS

Method parameters (typical)

Number of locationsCommonly 10 (as per protocol)
Sample sizeTypically 1–3 times the dosage unit weight
SamplerSampling thief (e.g. side-chamber or end-sampling type)
ResultEach sample as % of theoretical; report mean, minimum, maximum and %RSD
0125250375500012345678Active ingredienttR 3.9 minTime (minutes)mAU
Illustrative chromatogram — your retention time depends on the column and conditions.
BEFORE YOU REPORT

System suitability & sequence

ParameterLimit
%RSD of replicate standard injectionsTypically not more than 2.0% (as in the assay method)

Typical sequence

  1. 1Blank × 1
  2. 2Standard × 5 (system suitability)
  3. 3Location samples 1–10
  4. 4Bracketing standard × 1
CALCULATION

Calculation with a worked example

%RSD = (s ÷ X̄) × 100, where s = √[Σ(x − X̄)² ÷ (n − 1)]

Where

x
Result of each location sample (% of theoretical)
X̄
Mean of all location results
s
Sample standard deviation
n
Number of results (10)

Given

Results (% of theoretical)
99.2, 101.5, 98.7, 100.8, 102.1, 97.9, 100.3, 99.6, 101.0, 98.4

Working

  1. Sum = 999.5, so X̄ = 999.5 ÷ 10 = 99.95%
  2. Deviations from the mean: −0.75, +1.55, −1.25, +0.85, +2.15, −2.05, +0.35, −0.35, +1.05, −1.55
  3. Sum of squared deviations = 17.825
  4. s = √(17.825 ÷ 9) = √1.9806 = 1.407%
  5. %RSD = 1.407 ÷ 99.95 × 100 = 1.41%
  6. Range of individual results = 97.9% to 102.1%

Mean 99.95%, %RSD 1.41%: within typical criteria of mean 90.0–110.0% and RSD ≤ 5.0%.

Try it with your numbers
ACCEPTANCE CRITERIA

What result passes

  • Typical criteria: mean 90.0–110.0% of theoretical and %RSD not more than 5.0%. Use the criteria in your approved protocol or SOP.
  • Some protocols also set limits on individual results (e.g. each within 75.0–125.0%) or use tighter limits; follow your protocol.
METHOD VALIDATION

Validation parameters (ICH Q2(R2))

ParameterTypical requirement
MethodValidated assay method suitable for unit-dose-sized samples
SamplingSampling technique and thief shown not to bias results (sampling error can look like poor mixing)
In LimsPulse · Sample Management

Run this method in LimsPulse: specifications and STPs under version control, results calculated and checked against limits, and a signed Certificate of Analysis.

See how