Issue link: https://www.e-digitaleditions.com/i/1393031
Tablets & Capsules July/August 2021 25 Binder and lubricant. A high percentage of bind- ers and a low percentage of lubricants in a formulation improves compactibility. Mitigating compactibility issues Now that we've covered the factors that contribute to a formulation's compactibility, let's examine some ways to mitigate compactibility issues. Quality by Design (QbD). Experimentation at the R&D stage is much less expensive than in the manufac- turing stage. R&D should collaborate with manufacturing and strive to provide a robust process that provides good quality tablets while accommodating the expected varia- tions inherent in manufacturing. Allow the process to be flexible for continuous improve- ment. As part of QbD, develop and submit a multivariate array of critical parameters instead of fixed ranges. Mixing. Optimize procedures to prevent segregation of different particle sizes within a batch. Overmixing can lead not only to segregation but also to overworking the lubricant into the mixture. Blending before adding the lubricant is often helpful. Granulation. To improve a formulation's performance characteristics, often you must forego direct compres- sion and granulate the formulation using either dry or wet methods. Granulation joins particles to form larger, irregular agglomerates that compact more easily. Wet granulation, however, may change the API's crystalline structure due to the presence of solvent. Storage. Storing a mixture before compression can change its material properties. Common changes include alterations to moisture content and caking. Sitting in stor- age can also apply consolidation stress to the formulation. Minimize caking by reducing formulation storage time and the height of the storage drum. Particles near the bottom of the stored material receive more consol- idation stress than particles near the top. Tumbling the drum after storage can reduce caking effects by redis- tributing the formulation throughout the drum. Storage should always be in a room that's climate-controlled for both temperature and humidity. Tablet design. Optimize tablet design to help com- press formulations with poor compactibility. Generally, a flatter cup profile can improve tablet-hardness uniformity. Scaling the tablet's proportions becomes more import- ant with poorly compactible formulas. If your tablet is too thin or too thick, you will have more difficulty achieving target hardness. For convex tablets, the tablet thickness should be approximately 4 to 5 times the tablet cup depth and approximately two-thirds of the tablet's width, although you may need to adjust those proportions for large dosages. Tooling design. Optimize your tooling design. For formulations with a high strain rate sensitivity—which perform better at slow press speeds—increase the size of the punch head flat to extend dwell time and improve compaction. For formulations with low permeability, increasing the clearance between the punch tip and die bore can aid in air escape during tablet compression. Tapering the die bore can also increase air escape. A careful review of the keying angle for shaped tablets with marginal tablet strength is advisable. Also, there are countless variations in a tablet press' tablet stripper angle in relation to tablet geometry, and using the Tableting Spec- ification Manual (TSM) default of approximately 35 degrees may not be optimum for the gentlest ejection. Tablet press setup. For poorly compactible formula- tions, you should: • Control environmental conditions in the compres- sion suite for temperature and humidity. • Reduce the upper punch penetration to 1.5 to 2.5 millimeters to reduce the distance air must travel to escape the die bore during compression. • Use overload settings below the tooling force rat- ing. It can be helpful to establish an overload value that is approximately 20 percent higher than the average compression force used, as long as that number is below the tooling force rating. This allows the operator an opportunity to get feedback from the overload alarm if the formulation starts behaving outside a normal range of forces.