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.