Pharmaceutical Industry | Chemical Analytics | Measurement of Powdery Pharmaceutical Drugs

Monitoring the water content during spray drying of an active pharmaceutical ingredient

Drugs are indispensable to combat diseases. The effectiveness of a drug depends, amongst other factors, on the bioavailability of the active ingredient contained in the drug. It indicates the speed and extent to which the active ingredient enters the bloodstream. If the drug is not released in sufficient quantity or too quickly in the body, it remains ineffective (see figure 1).

Fig.1: Release profile: comparison of the drug concentration in the blood at different release rates

One of the most important challenges is the low aqueous solubility of the active ingredients. This hinders the bioavailability of orally administered drugs and requires special processing techniques. These and other parameters must therefore be continuously monitored to ensure the optimum efficacy of the end product.


Control of spray drying process

Measurement of powedery pharmaceutical drugs

Field of Application

Online-process control using NIR spectroscopy for precise measurements of the wanter content during the production of pharmaceutical drugs.  


Scope of Application

  • Measurement of residual moisture at the outlet of a spray dryer




  • Process Analytical Tecchnology (PAT)

  • NIR Spectroscopy

  • Diffuse Reflection Measurement



  • NIR Spectroscopy

  • Online/Inline

  • Conactless Measurement


Online measurements carried out around the clock help to make trends immediately visible and anticipate system disturbances that can lead to deviations.

The Challenge

For optimal effectiveness of the drug critical quality attributes such as particle size distribution, residual solvent content, bulk density and morphology must be monitored and controlled. A decisive and quality-determining process step in which the above-mentioned parameters can be influenced is the drying of an active ingredient dissolved in a solvent and mixed with excipient. A preferred method in this context is the process of spray drying. It is used to produce inhalable powder and obtain an amorphous solid dispersion.

Spray Drying Installation

During spray drying, various parameters must be closely monitored

During the process of spray drying, the complex interactions between the liquid to be dried and the heated gas can influence both the morphology and the particle size. It is important to keep these parameters within specific values since they can influence the release profile of the drug.  

The Application

Spray drying is used, for example in the manufacture of pharmaceutical intermediates. A great advantage of spray drying is that the contact between the spray material and the hot drying gas is very short, so that even thermally sensitive substances can be dried. Drying a single drop takes less than 1 second.

One parameter that must be continuously and precisely monitored during this process step is the water content in the powder. It is important that the residual moisture of the resulting powder complies to strict specifications. Deviations can affect the downstream processes, powder flowability and ultimately the performance of the drug.Typical effects when the residual moisture is too high are, for example, clumping and ultimately decrease on yield.

schematic illustration of the measurement setup with PAT technologies

Timely process monitoring is not possible with time-consuming sample analysis in the laboratory

The typical approach to determining the water content is the Karl Fischer method. This method implies taking samples and analyzing them manually in the laboratory. Not only is this very time consuming and requires material handling, the long period between sampling and analysis lead to a late response on process every time the water content deviates from the expected values. More efficient is the use of process analytical technology (PAT), enabling continuous monitoring of the relevant quality parameters and, at the same time, guarantees compliance to GMP-, ISO and ATEX standards.

You want to know how this measurement task was solved the best possible way?

A more detailed description on how this application was realized using online measurement technology can be found in our detailed application report, which you can download from the info column at the top of the page.


Hellma USA Inc.
120 Terminal Drive
11803 Plainview, NY
United States

Phone: +1 5169 3908 88


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Precise Monitoring of the Water Content During Spray Drying of an Active Pharmaceutical Ingredient


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