Purpose: Stickiness is a phenomenon that reflects the propensity of powders to agglomerate and to adhere to surfaces. Powder stickiness is related to this structural collapse and it is a problem frequently encountered during amorphous dispersions processing. The stickiness of powders may cause material losses in the pharmaceutical manufacturing processes (low yields) and can lead to clogging of the units and thus to the interruption of the process which is highly undesirable. The sickness propensity depends on the material properties, but in case of amorphous dispersions, it is an intrinsic function of their glass transition temperatures . In this study, a methodology to characterize the sticky temperature (Ts), was applied to characterize the Ts of an amorphous spray-dried dispersion and compared with the glass transition temperature of the material. Although sticky point temperature characterization is prevalent in the food industry literature [1,2], it is seldom used in pharmaceutical processes.The knowledge of the Ts contributes to a better definition of the design space of the spray drying and post-drying process conditions. Specifically, it allows quantifying the edge of a failure with respect to process yield and onset of caking and agglomeration at the equipment inner surfaces.This allows process scientists and engineers to achieve the best trade-off between particle engineering for optimal product performance and process performance with respect to yield and throughput.
Methods: The amorphous solid dispersion sample used for this study was produced in a laboratory scale spray-dryer Buchi (B-290). Differential Scanning Calorimetry (DSC) and X-ray powder diffraction (XRPD) analyses were performed in order to confirm the amorphous nature of the solid dispersion.
The sticky temperature of the amorphous sample was assessed using a modified program based on the Stability and Variable Flow Rate method, which is a standard method provided by the FT4 rheometer (Freeman Technology). The default SVFR method was modified to contain 13 test cycles in order for the powders to reach a stable state. In order to determine the sticky temperature of the spray-drying material, the sample within the vessel was heated at different temperatures with the help of a thermal jacket around the vessel. The spray dried dispersion sample was heated from 25º C to 75 ºC with an increment of 5ºC per test. The parameter used to assess the stickiness of the powder was the average of the Basic Flowability Energy (BFE) obtained in 13 cycles for each temperature. To check reversibility of this stickiness state, the material was also left cooling until room temperature after the determination of the sticky temperature. After reaching room temperature, a second analysis was made to the powder and a new BFE determination was carried out.
Results: XRPD and DSC confirmed the amorphous nature of the solid dispersion. A glass transition (Tg) of 61 ºC was determined. The amorphous solid dispersion sample was heated to 75ºC in a 35 mL vessel and the BFE (Basic Flowability Energy) was determined at different temperatures. The BFE results showed to remain constant (around 97 mJ) when the sample was heated from 25ºC to 65 ºC (Figure 1). A difference of only 0.4 % was found between 25 ºC and 65 ºC, indicating that the rheological properties of the material remained stable under this temperature range. However, when the temperature was increased up to 70 ºC, the average of BFE strongly increased: a difference of about 15 % when compared to the baseline value. This change of BFE measures the added energy required for the rheometer blade to move through the powder bed, which is likely related to a sudden rise of the material stickiness. This means that the material change dramatically its sticky properties close to 65 ºC. The material was then left cooling until room temperature and another BFE measurement was performed confirming that this phenomenon is reversible once it returned to lower values.
Conclusion: We propose a methodology to measure the temperature at which a spray-dried amorphous powder changes dramatically its rheological properties and becomes sticky, commonly known as “sticky point”. In the reported experiment, the sticky point occurred at a temperature slightly above the glass transition temperature which is consistent with the scientific literature for food processing. From process standpoint, it is conceivable to dry amorphous dispersions at temperatures above the Tg, which may be of use to broaden the design space for particle engineering without compromising the yield based on the knowledge of the sticky point of the material. Nevertheless, care must be taken to ensure that the exposure of the product to higher temperatures is short enough to ensure no phase separation or crystallization can occur. The proposed methodology is also useful for new generation ternary amorphous solid dispersions where a third component is added, typically a surfactant, which has a low Tg or melting point and thus contributes to increased product stickiness.