Particulate solids are unique materials because the particles can hold solid, gas and liquid phases at the same time. Small changes in temperature and even pressure can produce problems such as clumping, loss of efficacy (e.g., of an active ingredient in a pharmaceutical) and, sometimes, deflagration. While water or moisture often can pose issues, other solvents also can cause difficulties. Solvent needn’t be liquid to prompt a problem. So, understanding where the solvent is can play a critical role in solving these types of problems.
Solvent appears in four forms:
1. Free or surface. Drying easily will remove the solvent — presuming the particles stay in the dryer a sufficient time (and the unit provides uniform heat distribution). Most dryers are run based on the contact time or an exit temperature; an increase in either will give a dryer product but may alter the product’s color, taste or effectiveness.
Such solvent is the most common cause of clumping. To avoid this problem, determine the critical solvent content at the point where drying goes from a heat-transfer-limited condition to a mass-transfer situation. Not exceeding this critical point will prevent damage to the product from excess heat.
2. Bound. Here, solvent is physically or chemically adsorbed onto the particle by cohesive, chemical or electrostatic forces. (Many products actually depend upon this bound solvent for their effectiveness.) Often, the dryer must reach a specific temperature to drive off the solvent. Some types of dryers, such as batch vacuum dryers and fluid bed dryers with multiple drying zones, are better at removing bound solvent.
One often overlooked consideration in dryer selection is preventing solvent from rebinding to the product. Many products require cooling before removal from the dryer to prevent this from happening.
3. Inherent. Solvent molecules trapped inside the crevices of crystals or micropores of amorphous powders come into play when particles break. Drying usually can’t remove these molecules unless they explode. However, purging the product with dry gas, especially after a milling process, can minimize their effect. This group includes solvents of hydration or crystallization; these are stable forms whose release requires a phase change or chemical reaction.
Drying tests don’t identify this form of solvent. You must dissolve or micronize the particles to find such solvents. They cause the most trouble and often result in short shelf-life and clumping.
4. Interstitial. This usually stems from solvent vapor filling the voids of the bulk material. Even though the amount of solvent is very small, it plays an important role in caking mechanisms and chemical decomposition. Purging such solvent is fairly easy by fluidizing with dry gas.
To properly address problems, knowing the nature of the solvent is crucial. Eight methods for determining the solvent in a particulate solid are common. Some apply specifically to water. Each one can give a slightly different result, so it’s important to note the analysis method used (especially when communicating with customers). The methods are:
1. Karl Fischer — free and bound moisture (you can use other chemicals to titrate the solid to detect the presence of other solvents);
2. Loss on drying (LOD) — free or surface solvent and a major portion of bound solvent (for moisture, this usually is 90°C for 6 hours);
3. Infrared — surface moisture, which closely approximates free moisture;
4. Radio frequency — inherent (sometimes), bound and free moisture;
5. Microwave — total and interstitial moisture (using different wavelengths);
6. Loss on ignition — total solvent (can be done following LOD to get solvent of crystallization);
7. Thermo-gravimetric analysis — total solvent loss with time: differential thermal analysis (DTA) is a more precise variation for solvent flux (and can be combined with a gas chromatograph-mass spectrometer to identify chemicals in a multicomponent solvent system); and
8. Differential scanning calorimetry (DSC) — heat flow with time (especially useful in multicomponent solvent systems).
None will reveal all four types of solvent directly. However, you can run DTA and DSC in a manner to allow the computation of all four.