Robert Sedlock and Pratap Basim discuss the process and formulation considerations to avoid tablet defects
Tablet compression is still the preferred delivery system process for over-the-counter and prescribed medications. The process of compressing a block of particles is an art and science that must be understood for successful manufacturing. Tablet defects are commonly blamed on the tooling, tablet press, operators or the powdered formulation. When these issues arise at the manufacturing scale, there are techniques to battle common tablet defects, but when the root cause is the powdered formulation, it becomes very challenging to overcome.
During the development process, it’s critical to fully characterise the powder micromeritics and deformation properties. Natoli Scientific offers services to evaluate and formulate tablets for all applications. Formulation fundamentals must be understood and tested, which will ensure success at the manufacturing scale. Formulation characteristics, such as particle size distribution, moisture content, powder rheology, and material deformation nature, are the fundamental properties that will be explained in this paper.
Particle size distribution analysis for improved tablet production
A particle size distribution analysis gives an initial understanding about the powder blend tableting performance. A bimodal distribution of the powder blend with a combination of fines and large particles is an indication of the tableting failures on the tablet press. This is due to the smaller particles in a powder blend blocks the air escaping channels and reduces the air escaping tendency. As a result, entrapped air reduces the inter particle bonding and causes several tableting issues, such as capping, and lamination. A sample blend with a bimodal distribution (Fig. 1) yielded high capping behaviour. However, with a quick removal of fines (less than 70 micron) in the blend produced an intact tablet.
The impact of moisture content on tablet production
Although some degree of moisture is required to bind the particles into a robust tablet dosage form, it can also negatively affect the tablet, leading to adhered powder on the punch surface. The build-up of powder results in tablet defects, such as sticking. To clarify, sticking occurs when the adhesive forces of the formulation to the punch tip surface overcomes the cohesive forces within the tablet. A higher moisture content can increase the capillary action between the punch surface and the powder surface. These capillary bridges cause high adhesion areas, which results in sticking. It is worth emphasising that it is not only moisture within the formulation that can be problematic; moisture can also enter through the environment in which the tablet is compressed. Excess humidity in the compression room or areas where the formulation blend is stored prior to compression can also negatively affect how the formulation adheres to the punch tip surface.
One of the solutions to sticking is to apply an anti-stick coating to the punch faces. Natoli ultra coat, CrN and ZrN are popular coatings due to their anti-stick properties. These coatings are also helpful while compressing corrosive and abrasive materials (anti corrosion and anti-wear properties). The punch face surface finish (matte finish and mirror finish) is also an important factor in overall tableting performance and subsequently the sticking potential. Coating technology has advanced considerably over the years and when used in conjunction with high-quality tooling steel, tool coatings are increasingly becoming an acceptable means of solving production problems.
Powder rheology and tablet production
Powder properties, such as air permeability and powder cohesion, have great relevance to tableting issues, such as capping and lamination. Entrapped air reduces the inter-particle bonding and reduces the strength of the tablet, which eventually leads to tablet defects. A powder with high permeability and less cohesion has less chances of air entrapment.
Also, the process of compression can trap air in the concave cup of the punch face. The deeper the cup, the more likely it is to trap air. This trapped air creates a soft area on the very top of the tablet. In such cases, the granules don’t know whether to stick to each other or to stick within the punch cup. In this case, increasing compaction consolidation and or dwell time, applying precompression, utilising tapered dies and reducing upper punch penetration will be helpful.
Compaction emulator studying processing conditions and tablet deformation behaviour
Even products that meet above mentioned specifications may fail. You may not know how well a product will compress until it is on the tablet press. Processing conditions of the tablet press, deformation behaviour of the material, or it might also be a combination of the both factors can affect the tableting performance. One technique to study both factors together with a small amount of powder is a compaction emulation. A tablet press can be simulated using the realistic compaction conditions, such as interchangeable pre and main rollers and variable horizontal punch velocities reaching over 1m per second. An understanding of the deformation properties at manufacturing rates will serve as a tool in the formulation excipient selections process.
Deformation behaviour of the material at the realistic conditions of a rotary bench top tablet press at 40RPM speed was measured using the compaction emulator to predict the tableting performance in the manufacturing scale at the early development of the tablet dosage form (Fig. 3). This method was proven to be useful to determine the tableting performance in the early developmental stage.
Robert Sedlock and Pratap Basim are with Natoli