Powder Characterization for Formulation and Processing - Pharmaceutical Technology

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Powder Characterization for Formulation and Processing
The current trend within the pharmaceutical industry toward more efficient development, manufacturing, and specification is fueling demand for analytical tools that provide highly relevant information. Effective powder characterization has a valuable role to play.


Pharmaceutical Technology


Characterizing deaeration behavior

Although a degree of aeration is beneficial because it encourages continuous flow through the press, it is desirable that any entrained air is released easily as the powder settles in the die and is compressed. This release of air enhances dose-weight consistency and prevents tablet breakage that may occur when compressed air is released upon ejection of the tablet from the press.


Figure 5
Figure 5 shows the deaeration characteristics of three different lactose samples. Once the air supply has been removed, it is clear that both the spray-dried and coarsely milled lactose rapidly release air, and flow energy returns to stable, conditioned values quickly. The finely milled lactose, on the other hand, deaerates much more slowly because the air takes longer to permeate out from the powder bulk. These data correlate directly with the likelihood of tablet capping as a result of air release postcompression.

Optimizing compressive strength

A process closely related to direct-compression tableting is the production of compacts for blister filling. Like tableting, this process involves die-filling and subsequent compression of a dose. The compressing force, however, is much less: around 10 kPa rather than the MPa stresses used for tableting.


Figure 6
For this process, an optimum level of cohesion and other mechanical properties are required to form stable compacts or plugs under the application of moderate compressive force. Excessively cohesive materials adhere to the punches, thus compromising dose uniformity and production rates. Figure 6 shows measurements made during an experimental investigation of the effect of flow additive on the properties of a pharmaceutical blend.

As the concentration of flow additive rises, compressive strength (as measured by shear stress) falls. Initially the material is so cohesive that it adheres to the punches during compression. As compressive strength falls, there is a range over which good-quality compacts are produced, but then, below a certain compressive strength, the compacts fall apart upon ejection. The optimal compressive-strength range is clear.

The way forward

The pressures on the pharmaceutical industry are catalyzing change. Designing quality into the product and manufacturing process (quality by design), monitoring and controlling processes to consistently produce the correct material (process analytical technology), and the long-term trend toward continuous processing are all evidence that the sector recognizes the need to work more efficiently. The success of such approaches ultimately rests on the development of better understanding.

Although powders present a challenge to the formulator and processor, modern powder-characterization techniques have much to contribute. Correlating various powder properties—shear, bulk, and dynamic—with product performance or processing behavior develops understanding of the properties that are critical for a given application. This approach allows experience to be quantified in terms of parameters that can be measured reproducibly. The experience that A processes well while B is much worse can be converted into knowledge that A processes better than B because it has a BFE in the range x to y, a compressive strength of z, and deaerates after only two deaeration cycles. The approach remains to some extent empirical, but it is vastly superior to development and operation that depend solely on experience.

State-of-the-art powder testers offer a suite of testing methodologies in a single instrument, thus providing access to the necessary data. The information opens up a route to better understanding and the development of transferable knowledge. These systems have an important role to play in helping the pharmaceutical industry conquer the complexities of powder processing and more effectively develop new products.

Tim Freeman is the director of operations at Freeman Technology, Boulters Farm Centre, Castlemorton Common, Welland, Worcestershire, WR13 6LE, UK, tel. 144 1684 310860, fax 144 1684 310236, http://www.freemantech.co.uk/

Reference

R. Freeman, "Measuring the Flow Properties of Consolidated, Conditioned, and Aerated Powders—A Comparative Study Using a Powder Rheometer and a Rotational Shear Cell," Powder Technol. 174, 25–33, (2007).


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