Avoiding surprises: How to achieve a robust tablet formulation strategy
Natoli Engineering discusses some of the important raw material characterising techniques to provide readers with a robust tablet formulation strategy from the development arena to the manufacturing environment.
Tablet compression is an established manufacturing process with numerous applications in pharmaceutical, nutritional, food, cosmetic and other industries. Compressing a block of particles into a single compact is a combination of art and science. With today’s technology, science is prevailing.
Underestimating the tablet design, formulation development and manufacturing process, could certainly cause significant problems at some stage of the product’s life. Many common tabletting defects arise due to the failure of fully understanding the raw material properties and how they are subjected to the tabletting process.
Discussion
Powder Rheology
Powder flow is a fundamental attribute required for successful tablet manufacturing. The powder must flow from the tablet press hopper to the feeder system and fill the die cavity in a homogeneous manner. If the powder doesn’t have sufficient flow properties, the resulting tablet weights will not be uniform, causing many issues, including API (Active Pharmaceutical Ingredient) content uniformity and tablet density variation, which leads to dissolution issues and other tabletting challenges.
Utilising powder rheology equipment, like the FT4 from Freeman Technologies, gives scientists insight on the powder properties and helps identify potential issues on the tablet press. First, you must understand the environment of each stage and what measurements are available.
Basic flowability energy (BFE) is one of the experiments to consider before tabletting. This fundamental test will give insight on the flowability of the materials. This is defined as the energy required to initiate the powder flow. High energy indicates poor flow of the powder, which causes weight variation and compaction pressure issues during the tabletting process. Figure 1 depicts examples of two API's, different ProSolv (JRS Pharma, Silicified Microcrystalline Cellulose) grades and ratio mixtures. ProSolv grades provide the highest BFE values and the API’s provide the lowest BFE values, according to the chart. This is typical, as most API’s have flow and compactibility issues, and ProSolv is an excipient that formulators add to the blend to improve flow and compactibility.
Powder permeability is another fundamental property affecting the tabletting process. Entrapped air in the powder blend reduces the interparticulate bonding and reduces the final tablet tensile strength, which leads to tablet failures, like capping. High permeability indicates less air entrapment during the tabletting process and fewer tablet defects. The highest permeability values are the ProSolv grades and the lowest are the API’s.
Another FT4 measurement is the sticking index. While not mentioned above, sticking is one of the most common tablet manufacturing issues. Moreover, at the manufacturing stage, formulation changes require a process following SUPAC (Scale-Up and Post Approval Changes) guidelines, which can be time consuming and halt production. Tool manufacturers offer punch tip coatings and special steel types to combat sticking issues but having insight of the formulation at early stages allows the scientist to modify the formulation and select the proper tools for a successful process.
Punch sticking results from the adhesion behaviour of the powder blend to the punch. This is quantified using the adhesion and cohesion behaviour of the powder. Adhesion behaviour was quantified using the ratio of the wall friction angle to the angle of internal particle friction. A higher sticking index indicates the higher sticking tendency. Figure 3 shows that IBU has the highest sticking tendency and adding Prosolv increases cohesiveness, which reduces adhesiveness and sticking. There are other factors that cause punch face sticking, like excessive particle fines, high moisture content, worn tooling and punch tip configuration, but the sticking index is another fundamental powder test before tabletting.
Material Deformation Properties & Compaction Emulation
Characterising the mechanical properties of raw ingredients is another vital test in developing a robust tablet formulation. Compaction emulators (Presster Image 1) are a material sparing compaction machine (<1 gram) that offers sophisticated instrumentation measurements. The emulator characterises the mechanical properties of the raw ingredients and emulates the manufacturing tablet process by matching the compression times of the desired manufacturing tablet press. Below is a chart of the available instrumentation, the measurement type and the analysis advantage.
Conclusion
Characterising powder rheology and mechanical properties provides science-based data for the tablet development process. Unwanted surprises at manufacturing scale are minimised by understanding powder rheology and utilising compaction emulators at development scale.
Special acknowledgements to Freeman Technologies, JRS Pharma and Pratap Basim, Dr. Rutesh Dave at Natoli Institute / Long Island University Arnold and Marie Schwartz College of Pharmacy in Brooklyn, New York.