Process Analytical Technology

Results

The data provided by the ESP™ is graphically characterized in a “funnel” shape as the relative standard deviation of the individual sensor readings decreases, indicating the optimal blend time.

The ESP™ delivers information about blend uniformity previously unavailable in real time. The data is obtained without thieving, so containment is never compromised. The results obtained with the ESP™ demonstrate strong correlation to wet chemistry techniques, and have been validated by other tests of uniformity, including HPLC and LC.

Effusivity readings from 8 networked sensors - strategically located on the lid of the blender - are taken every few minutes during the blending process. As the blending continues, and the material becomes more and more uniform, the sensor readings will be closer in value, until a point of smallest deviation is reached in the results. This is the point at which uniformity is optimized and blending should stop. Beyond this point, de-mixing or de-blending will occur and the effusivity readings from each of the sensors will start to separate.

Note: In the example illustrated above, there is an overall upward trend to these results that is a result of interstitial packing of the particles as they mix. The magnitude of this trend will vary on particle size, but has no influence on the measure of variations between sensors at a particular time.

  

Screen information generated by the ESP™ shows test result data captured during a test at Patterson-Kelly using a 3 sensor version of the system.

Online, Real Time Results Without Thieving

A key benefit of the ESP™ blend uniformity monitoring system is its ability to provide online evaluation, during the actual blending process. This eliminates the need to stop the blender to thieve samples for evaluation – and the resulting bias that is introduced in the thieving process. By providing real time results, the ESP™ also replaces the time time-consuming analysis of thieved samples using HPLC or other method .

The ability of the ESP™ to provide instant results during the blending process offers the following benefits:

  • Time and cost efficiencies in the scale up of new formulations
  • Uniformity verification on a more frequent basis for formulations currently in production
  • Reduced ingredient settling
  • Improved quality assurance
  • Reduced liability
  • Fewer discarded batches

Validation of ESP™ Results with HPLC Analysis

The following data, provided by an undisclosed ethical pharmaceutical company, demonstrates the agreement of test results evaluated using the ESP™ and HPLC. The formulation being tested was comprised of the elements listed below, and the projected effusivity value of the finished blend was calculated:

Blend Ingredient

% Blend Contribution

Mean Effusivity
(Ws1/2/m2K)

Projected Blend Effusivity

CR Polymer 17.66 364.7 406.75
Enteric Polymer 5.03 380.4
Dilutent 74.94 427.0
Active 2.37 165.6

The test procedure involved thieved samples taken from the top, middle and bottom of the blender at the following intervals: 5, 10, 20, 25, 30 and 35 minutes.

% RSD by Effusivity and HPLC

Time
(Minutes)

% Relative Standard Deviation by Effusivity

% Relative Standard Deviation by HPLC

5 1.2 1.1
10 3.6 3.1
15 1.4 2.6
25 1.5 0.8
30 2.9 2.3
35 3.2 1.2

Key Points of Agreement

  

The results demonstrate important correlation of the data between the two analysis methodologies:

  1. There is agreement on the low RDS that took place early in the blend at the 5 minute point
  2. There is agreement on the lowest RSD – the point of optimized blend – at the 25 minute point of the blend
  3. The projected blend effusivity that was calculated based on the formulation ingredients and their percentage in the mix was equal to the actual measured endpoint (406 Ws1/2 / m2K)

For information on pharmaceutical equipment manufactures, visit the following companies:

Request for Testing









Please select the information package you would like to receive.







Note: samples are disposed of 2 weeks after release of test results unless client notified C-Therm of their desire to have the samples returned (client's expense). Any hazardous materials that cannot be disposed of in municipal waste will be returned to client for disposal (client's expense).