Powder Characterisation for Formulators
The goals of formulation
Accelerating product development through formulation into successful manufacture and on to the marketplace, is an important goal for the pharmaceutical industry. Optimising the formulation process and more efficient production are strong themes as revenues come under intense pressure. For formulators the principal focus is developing a product that delivers desirable clinical performance, but manufacturing demands are increasingly influential. Steps taken at an early stage to thoroughly scope the links between process and product variables, as advocated by Quality by Design (QbD), can pay dividends over the long term. This is particularly true for powders, where optimisation of the formulation and process, in combination, builds quality into manufacturing from the outset.
Cost-effective tools for sensitive and relevant powder characterisation are an essential part of the formulator’s resources. Universal powder testers are especially useful, their value deriving from a unique combination of features which crucially includes:
- Multi-faceted powder characterisation (shear, bulk and dynamic properties)
- Exemplary reproducibility
- Process relevant measurements
Relevant, reproducible testing
Describing a powder using an array of variables rather than a single number is now widely accepted as the optimal approach since the complexity of powder behaviour cannot be adequately captured using just one descriptor. Instruments that offer multiple measurement strategies are an efficient way of gaining maximum insight, making it easier for formulators to identify and accurately measure the unique powder properties that correlate with specific aspects of clinical performance. For example, research has shown that the aerosolisation characteristics of dry powder inhaler formulations correlate directly with aerated flow energy. This parameter is only accessible via dynamic powder testing so this correlation would be missed using conventional, single parameter tests.
Excellent reproducibility enhances the sensitivity of any analytical instrument, sharpening the quality of the data. The correlation of different variables is severely hampered by ‘noisy’ data that can make it impossible to tell whether differences between samples are real, or simply measurement inaccuracies. For the formulator, sensitive analysis therefore provides fine detail, enhancing understanding of the factors influencing product performance.
Finally, process relevant data means that researchers can predict the in-process behaviour of a powder with just small amounts of sample, offering the opportunity to formulate on the basis of process understanding and control, as well as clinical performance. Producing a database of reproducible powder properties helps to break down the traditional barriers between formulation, process design and operation, promoting a more holistic multidisciplinary approach to development that captures the knowledge of different disciplines. Lessons learned during pilot and full-scale operation can inform new development if the information can be fed back upstream. For example, the manufacturing team may know that formulation A performs well in a vacuum vial filling process while formulation B is more problematic. Analysing the powders reveals that the poor performance of B can be quantified in terms of its permeability and the impact on flow properties (Basic Flowability Energy) induced by applying a vacuum. This is valuable information for formulators developing a new product that will be processed in a similar way.