Spray-dried a-lactose monohydrate is a matrix of amorphous lactose in which lactose monohydrate crystals are embedded. Humidity has no influence on the crystal but amorphous lactose is very hygroscopic: in presence of humidity, it will transform into the crystalline form. This has consequences on the tableting properties of the substance. Thermal Analysis gives you first Information about the water content of your lactose and the consequences for its compressing properties.
Spray-dried lactose is a matrix of amorphous lactose in which lactose monohydrate crystals are embedded. Humidity has no influence on the crystal but amorphous lactose is very hygroscopic: in the presence of humidity, it will transform into the crystalline form. This has consequences on the tableting properties of the substance.
Storage in a humid atmosphere leads to caking!
How to be sure that the delivered lactose has the correct properties prior to processing? For that, you only need a measurement with a thermogravimetric balance. This instrument records the mass changes of a sample during heating. An example of the measurement carried out on spray-dried α-lactose monohydrate is given in figure 1.
4 mass-loss steps are recorded, giving information about:
Surface water content in the sample (0.5% of initial sample mass)
Crystal water content (4.5% of initial sample mass)
Thermal decomposition (beginning at 224°C, leading to 2 steps of 8.2 and 70.8% mass loss)
The spray dried Lactose was stored 2 weeks in a humid atmosphere. The same measurement was then carried out on this sample. The TGA curve is displayed in figure 2 (blue curve). It is immediately clear that the amount of surface water increased during storage in a humid atmosphere (0.5 to 4.5%).
An increase in water amount can lead to caking, and thus to problems during processing.
Storage in a humid atmosphere influences the tableting properties!
Storage in a humid atmosphere also increased the amount of crystal water. For the monohydrate form of lactose, a molecule of lactose is associated with one molecule of water. This means that it is possible to calculate the amount of α-lactose monohydrate in the sample by using the amount of crystal water! Pure α-lactose monohydrate contains 5% crystal water.
Let us calculate the amount of crystal water without taking surface water in consideration: It amounts to 4.54% for the sample as received and 4.95% for the sample after storage in a humid atmosphere. The storage led to an increase of α-lactose monohydrate in the sample!
Water acts as a plasticizer and leads to the molecular mobility of the amorphous domains of lactose. As a consequence, the amorphous phase can crystallize as a monohydrate.
However, it is precisely the amorphous phase of spray-dried lactose that yields good compression properties of the product. That´s why this crystallization of the amorphous phase should be avoided.
Measurement by means of a thermobalance ensures good quality of the substance for easy processing and good tableting properties.