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Tim Freeman of Freeman Technology explains how new analytical technologies have influenced quality criteria and standards for the uniformity of dosage units, and why more accurate systems are leading to greater focus on tablet scoring.
How has the development of new analytical technologies influenced the quality criteria and standards for the uniformity of dosage units? Have more accurate systems led to greater focus on tablet scoring?
Tablet scoring enables patients to control their drug dosage and could potentially deliver cost savings for healthcare providers. It also makes larger tablets easier to swallow. However, the production of a scored tablet undoubtedly adds complexity to the manufacturing process. This issue was brought into focus by recent FDA guidance on tablet scoring, for both general tabletting, and more specifically, the manufacturing of generics.
Whilst a key aspect of tablet splitting has always been on how uniformly the active ingredient is distributed within the finished product, it is equally important to understand how to produce tablets with the required mechanical integrity and properties. Advances in spectroscopic techniques, such as near infrared (NIR) and laser-induced breakdown spectroscopy (LIBS), mean that it is now possible to analyse content uniformity across the surface of a tablet. In addition, advances in powder characterisation techniques can assist in the development of truly robust manufacturing processes.
Poor content uniformity is often attributed to the difficulty of achieving a homogeneous blend to begin with, which may be because the active ingredient is present at very low levels, or is cohesive and prone to agglomeration. Alternatively, if the API has significant particle size or density difference to the excipients in the blend, it may be liable to segregation post blending. Dynamic powder characterisation can help optimise the blending process (1) and also predict the likelihood of segregation. It therefore brings real insight into how to address these issues.
Furthermore, dynamic parameters in combination with shear and bulk properties, support a comprehensive understanding of powder behaviour, whether during the blending process itself, or when processed through the tablet press. Together these properties help manufacturers to rationalise and control powder performance during discharge from the hopper, whilst flowing through the feed frame, and during filling of the die. In addition, they provide information relating to the compressibility characteristics of the blend, as well as quantifying the ease with which air is entrained and released, both of which impact finished tablet quality. This information can be extremely helpful in ensuring compatibility between the process equipment selected and the properties of the blend, a match that is crucial for ensuring content uniformity in scored tablets.
When manufacturers are developing a tablet designed to be scored or subdivided, what tests are necessary to ensure stability? How does patient compliance factor into these decisions?
Stability raises issues around the mechanical properties of the tablet, for example, can it be broken into two equally useful doses without crumbling, and is the finished product stable despite the score? Once again, powder characterisation can play a useful role here in product and process optimisation. For instance, one of the factors that influences tablet hardness and friability is the consistency of the die filling, which in turn is impacted by the characteristics of the powder blend. Even if the die can be filled uniformly at a commercially viable press speed, it is vital that the entrained air is rapidly released during compression and compaction, as retention can lead to capping and lamination. Retention is especially a problem for larger tablets that are more likely to be scored. The ability of the blend to release air can be quantified using parameters such as permeability and through dynamic characterisation of aerated powders. Finally, the response of the powder to compression can be directly measured via compressibility testing. In summary, comprehensive multifaceted powder characterisation supports the development of optimised formulations and more exacting processes, both of which are required to produce well-engineered, mechanically stable scored tablets that are easy for patients to use.
FDA is currently working on draft guidance for tablet scoring. If implemented, how could such guidance affect analytical approaches for scored tablets, both in terms of new developments and demands from the industry?
Increased focus by the FDA on scored tablets intensifies the requirement for manufacturers to adopt a rigorous quality-by-design (QbD) approach to their tablet development processes. Analytical approaches that can lead to a better understanding of critical-to-quality parameters, such as content uniformity and mechanical stability as outlined above, are therefore likely to become increasingly important. Properties that predict blending performance and how the blend will subsequently perform in the tableting press are especially valuable. For example, returning to the issue of air entrainment and release, processing powders with low permeability at high rates can ultimately lead to trapped air building up in the powder at all stages of the press due to fast powder flow rates and recycle. The net result is an eventual degradation in tablet quality. This is just one of many illustrations of how powder property data can help processors make sound decisions about what equipment to use and what production rates to target for efficient scored tablet manufacture.
1. Blending white paper at: http://www.freemantech.co.uk/en/literature-and-downloads/articles-and-white-papers.html#white-papers