During the tablet manufacturing process, tooling and press manufacturers are often faced with ongoing challenges. As a tooling and press manufacturer, you should be able to expect support from your partnering vendor during all aspects of the compression process. These services should include press operator training, maintenance /calibration services, quick delivery parts, tooling/ tablet design, and powder formulation support.
If any compression issues occur, these services act as a support tool to help you overcome manufacturing challenges. However, if there is a change in formulation, a process following Scale-Up and Post Approval Changes (SUPAC) guidelines must occur before moving forward. Time-consuming and often frustrating, the SUPAC process is guaranteed to halt manufacturing and should be avoided.
This article will review the importance of the formulation development process and how a thorough approach can reduce manufacturing issues, costs, and downtime. The case studies provided in this article were performed at the Natoli Institute for Industrial Pharmacy Research & Development — Arnold and Marie Schwartz College of Pharmacy and Health Sciences on the Brooklyn, NY campus of Long Island University.
For both formulators and research professionals, developing a tablet formulation that is both robust and able to be scaled into manufacturing without issue can be a challenge. Tasked with this, formulators and research professionals use their understanding of the science side of powder compaction to effectively communicate with scale-up and manufacturing groups – increasing return on investment and reducing time to achieve a marketed product.
Single-station tablet presses offer many advantages during early development, such as requiring a limited amount of material to characterise potential formulations. With only a few milligrams of material, the die-filling process can be performed manually. Characterising just the API can also be performed on these machines allowing the scientist to select the appropriate excipients based on the results of the compacted API.
Figure 1 (below) is a tablet ability profile performed on the NP-RD10A single-station tablet press. This is an example of evaluating a high drug load directly compressible APAP formulation (DB) versus a wet granulation APAP formulation (WG).
Instead of collecting the data using compression force (kN), there is an advantage to normalising the punch tip face area and utilising compaction pressure. With any new formulation the required compression force is based on the material properties and tablet size. Performing a compaction study from 50MPa–300MPa covers the normal ranges for compressing pharmaceutical tablets of all sizes.
Furthermore, the tablet tensile strength is a normalisation of the tablet geometry. Target hardness or a breaking force value (kilopond or Newtons) cannot be determined until further testing is performed. Target tensile strength of 1–2MPa are representative values for a robust tablet that will withstand handling, friability, and coating operation.
The profile clearly shows that the wet granulation blend yields stronger tablets than the directly compressible blend throughout the compaction pressure ranges. Although there is a cost advantage with directly compressible blends as the equipment investment costs and process times are much lower. The next step in the process is to perform additional studies on a rotary tablet press.
