Figure 1. The correlation between thermal effusivity and loss on drying (LOD) is shown for four powders hydrated with water.10,11,12

The main goals of using online monitoring are to improve manufacturing efficiency and product quality. Online monitoring provides a "process check" that occurs within the actual unit operation being performed. This enables the modification of a process in response to measured fluctuations, making it possible to achieve better product consistency. Online measurements also allow you to:
  • Eliminate sample removal.

  • Reduce process time by reducing cycle interruptions.

  • Reduce operator exposure to products during sampling.

  • Provide insurance against batch failure.

For these reasons, online monitoring methods such as near infrared (NIR), acoustic and thermal effusivity are an important addition to at-line or offline measurements used for end-point determination (e.g., outlet air temperature, time, loss on drying). This article will take a closer look at one online moisture measurement technique, thermal effusivity.

Effusivity is a heat transfer property present in all materials in all formats: solid, liquid, paste, powder and gas. Effusivity combines thermal conductivity, density and heat capacity into one value.

Effusivity is the property that dictates the interfacial temperature when two objects at different temperatures touch -- i.e., when you touch a piece of metal vs. a piece of wood. The effusivity of materials varies due to their differing ability to transfer heat. This is due to differences in heat transfer through and between particles, and is therefore a function of particle size, particle shape, density, morphology, crystallinity and moisture content.1,2,3

The thermal effusivity of a sample will be driven by the properties of its composition and the properties of the inter-particle material (e.g., air, water, polymers, solvent). The effusivity of water is 1,600 Ws 1/2/m2K, whereas the effusivity of solid powders typically varies between 50 and 1,000 Ws1/2/m2K. For this reason, a 1 percent increase in water content raises the effusivity of a typical powder by 3 percent. This makes it possible to use effusivity as a drying monitoring tool. During drying, the effusivity will decrease as water is removed, and the results will follow the same expected trend as loss on drying (%LOD) measurements.

Effusivity can be measured directly.4,5,6One method involves an interfacial device that places a sensor in direct contact with the sample and is used to measure heat flow. The rate of heat transfer from the instrument's heating element is a function of the thermal effusivity of the sample material (wetter material absorbs more heat). For more information on the effusivity method and apparatus, refer to the ASTM E55 standard or USP Chapter <1073>.7,8

Figure 2. Four batches of a pharmaceutical powder were granulated with PVP 29-32 and dried in the same fluidized bed under identical operational conditions. The correlation between thermal effusivity and LOD has a resolution of 0.5 percent.10

EFFUSIVITY AND MOISTURE CONTENT

Successful process monitoring relies on the ability to collect representative samples from the process and to have a robust, reliable measurement method. Diverse types of powders -- Lactose Fast Flo, microcrystalline cellulose, dicalcium phosphate granular and alumina hydrate -- with water have shown effusivity to have a strong correlation with moisture content (figure 1). The same correlation, effusivity vs. moisture content, was observed with a powder that was granulated using four different binders. In all cases, the slopes of the regression varied for each powder and binder. It is hypothesized that this is due to differences in the binder-excipient interaction. The greater the slope, the more sensitive effusivity is to the moisture content of the material.

The effusivity method demonstrates the ability to measure a wide range (LOD 0.3 percent to 46.9 percent) of moisture contents in several products with a sensitivity down to 0.25 percent.

Real-Life Example. Four batches of a pharmaceutical powder were granulated with PVP 29-32 and dried in the same fluidized bed under identical operational conditions. The results of the four batches are summarized in figure 2 and show that effusivity measurements of the moisture content are consistent from batch to batch.

Figure 3. Offline effusivity testing techniques include the regular method (left), in which the sensor is placed on the material, and the inverted method (right), in which the material is placed on the inverted sensor.

To conduct effusivity measurements, the material needs to be in contact with the effusivity sensor for a short period of time (1 to 10 sec). Other conditions requiring consideration include:

  • The conditions of the process (e.g., whether the material is static or in motion).
  • The nature of the material to be dried (particle size, moisture range, etc.).
  • The information sought (moisture alone or uniformity as well).


Offline Monitoring. During the first part of a feasibility study, the effusivity equipment can be used offline until full-scale trials are warranted. The offline measurement requires that the samples are extracted from the process and brought to the effusivity instrument to be tested. The offline effusivity measurements can be done using one of three techniques, depending on the powder properties and desired precision:

  • Placing the sensor over the material to be tested (figure 3).
  • Placing the material on the sensor, which is in an upright position (figure 3).
  • Using the offline effusivity-testing cell to apply a constant pressure on the fixed-volume sample against the sensor (figure 4).


The offline technique is helpful when developing a process; when optimal sampling locations are not known; when extraction of the samples from the process is simple and representative; and when samples can be analyzed in a timely manner after they are extracted from the process.

The offline technique is not recommended if the process conditions or the material can be hazardous to the operator; if the process needs to be stopped for sampling and the process interruption may impact the product quality or process efficiency; or if the sample cannot be extracted from the process.

At-Line Monitoring. With at-line monitoring, the effusivity measurements are taken at-line using an in-situ method using one to eight effusivity sensors in a simplified "plunking" technique. In other words, effusivity is measured by placing the sensor(s) in contact with the material inside the processing unit.

Like the offline monitoring method, the at-line technique is helpful when developing a process, when optimal sampling locations are not known and when sampling is complex. It also is useful for applications where the sample moisture content fluctuates when the sample is extracted from the process, when a sample cannot be extracted from the process or a representative sample is difficult to obtain, and when mapping is important.

The at-line technique is not recommended if the process conditions or the material can potentially be hazardous to the operator; if the process must be stopped for measurements to be taken and the process interruption may impact product quality or process efficiency; or when containment is required.

Online Monitoring. An effusivity system can be integrated into the dryer control board for online monitoring. The online technique uses an automated system that extracts the sample from the dryer, subsequently tests it under reproducible conditions, and then returns it to the dryer if required. The return of the sample is critical if the batch is small as in research and development or when containment is critical to process integrity.

As a result of the speed of this technique, it is possible to increase the number of data points collected in a process and thereby improve the accuracy of the final moisture content determination. Furthermore, the additional data results in more process knowledge, which is critical when optimizing the drying operation. Also, some effusivity sampling systems have the ability to sample several locations in the dryer and map the moisture content of the material at different stages of its drying cycle, allowing optimization of sampling locations and/or process conditions.

The online technique is helpful when tight moisture content end-points of final product need to be reached; when containment is required; when the material cannot be removed from the process; when the process cannot be stopped; when drying cycles need to be optimized; when fully automated monitoring or process unit control system is required; and process conditions and the material can potentially be hazardous to the operator.

The online technique is not recommended if the dryer is very small and does not have an existing pick point.

Figure 4. The offline effusivity testing cell consists of an effusivity sensor (A), pneumatic compression system (B), sample introduction port (C), the effusivity testing chamber (D) and the sample discharge and cleaning port (E).9

CONCLUSION

Effusivity correlates to the moisture content of several products and over a wide range of moisture content. The method has demonstrated robustness for batch-to-batch monitoring of the same material.

As a result of the speed of the technique, there is the ability to optimize, monitor and control drying processes with less time and effort than traditional methods, thereby improving overall product quality while minimizing costs in the manufacturing process.

Offline and at-line effusivity monitoring can be useful when optimizing and developing new products or processes. Because effusivity measurements take only a few seconds, online monitoring allows the operator to have real-time feedback regarding the status of the process. Online effusivity monitoring can be useful in process scaleup, optimization, monitoring and control. It eliminates sampling, reduces process time by reducing cycle interruptions, reduces operator exposure to products during sampling, and lowers batch failure rates. An online effusivity monitoring system can be fully automated and integrated to the control board of the drying unit. PH

References

1. Ligi Mathews, Prasad Adusumilli, Stanley Lech, Nancy Mathis and Bhagwan D. Rohera, "Effect of Physicochemical Properties on Thermal Effusivity of Pharmaceutical Excipients," poster presentation at the American Association of Pharmaceutical Scientists, November 2001.

2. "Thermal Effusivity: A Novel Technique for Raw Material Quality Control: Microcrystalline Cellulose," Joint technical note published by Mathis Instruments Ltd. and FMC Biopolymer, October 2003.

3. Yves Roy, Stephen Closs, Nancy Mathis and Enrique Nieves, "Thermal Effusivity as a Process Analytical Technology: To Optimize, Monitor, and Control Fluid-bed Drying."

4. N.E. Mathis, "New Transient Non-Destructive Technique Measures Thermal Effusivity and Diffusivity," Thermal Conductivity 25, Technomic Publishing, 2000, p. 3-14.

5. Nancy Mathis, "Method and Apparatus for Monitoring Substances," US Patent Pending US 10/482,049, application dated June 2001.

6. Nancy Mathis, "Method and Apparatus for Monitoring Substances," US Patent #20040165645, August 26th, 2004.

7. "Thermal Effusivity of Solids, Powders, Semi-solids, Liquids and Composite Samples using the Modified Hot Wire Technique," Submitted and to be published during 2004 by ASTM Committee E55 on Pharmaceutical Application of Process Analytical Technology.

8. "Effusivity," U.S. Pharmacopeia General Information Chapter 1073, USP Forum, Vol. 30, No. 4, July/August 2004.

9. Yves Roy, Régis Bots and Normand Dubuc, "Online Monitoring of the Moisture Content of Pharmaceutical Granules in a Fluid Bed Drying Process Using Thermal Effusivity: A Fully Automated System," technical document, July 2004.

10. Enrique Nieves, "Fluid Bed Granulation Drying Process Monitoring using Effusivity Technology," IFPAC 2004, Arlington, Va., January 2004.

11. Stephen Closs, Jason Boodram, Sanjay Samudre, Murray Adams, Colin Minchom, Nancy Mathis and Yves Roy, "Optimizing Pre-Blend Uniformity to Overcome Dead-Spot Issues in a High Shear Granulator using Thermal Effusivity Measurements," presentation at Interphex 2004, New York, March 2004.

12. Brad Canney, "Differentiating the Amount of Water During Drying Using the Mathis BT System," Mathis Instruments Technical Report. Fredericton, N.B., August 2004.

Links