(W1030-10-55) Optimizing Tablet Formulation through Integrated Use of Digital Formulation Tools and Compaction Simulation

Purpose: The aim of this study was to optimize the formulation and production process of pharmaceutical tablets using an integrated approach involving algorithm-based formulation tool (ZoomLab) and a compaction simulator (STYL’One Evo). This comprehensive workflow was designed to enhance tablet quality and manufacturability by leveraging cutting-edge digital and experimental tools and techniques.

Methods: The model drug ibuprofen Ibuprofen 70 was used in this study. It was characterized for particle size distribution (PSD), flow by angle of respose, and tabletability, compressibility, and compactibility profile. Using compaction simulator, STYL’One Evo. An online, free algorithm-based digital tool (ZoomLab) was used to predict the processability of Ibu and co-processed blend Kollitab DC 87L at various drug loadings. The tool predicted blend properties using mixing rules of single-component data (1). Based on the prediction, a simple direct compression method was selected for compaction simulation at 20% and 30% drug loading (DL) in round tablet, 10 mm in diameter, weighing approximately 400 mg. The selected formulations were then characterized using the compaction simulator, to assess critical properties such as compactibility, compressibility, and tabletability according to USP 1062 (2). Based on the characterization data, a small lab-scale batch was produced using an XL100 R&D rotary tablet press. This integrated workflow allowed for the precise adjustment of formulation and processing parameters to achieve optimal tablet quality.

Results: This study utilizes Kollitab DC 87L, a co-processed excipient that contains lactose (filler), Kollicoat IR (binder), Kollidon CL-F (disintegrant), and sodium stearyl fumarate (lubricant), for a blend with good flowability, compressibility, and lubrication properties. The use of the digital formulation tool facilitated the identification of the drug developability classification system (DCS) for development into a suitable dosage form and also helped predict processability of suitable powder blends properties containing the API and the co-processed excipient for the direct compression process (DC). Further adjustments to the processability of formulations were predicted using the compaction simulator. The algorithm-based tool predicted a processability score of 7.3 (out of 10) for the blend at 20% drug loading (DL) and 7.0 at 30% DL (Figure 1). Processability values of 10 are considered ideal while values between 5-10 are considered good for DC process (1,3). Based on the predicted processability values, the 20% and 30% drug loading and DC as a processing method was selected for experimental runs. Furthermore, the tool predicted the tabletability profile of Ibu tablets at various compression pressures and suggested a tensile strength of approximately 1.6 MPa at a compression pressure of approximately 114 MPa for both drug loadings (20% data is not shown) (Figure 1C). The tabletability plot of the blend at 20% and 30% DL illustrated a simulated decline in tablet strength with increasing drug loadings (Figure 2). As predicted in the digital tool, at a compression pressure of around 114 MPa, the tablet tensile strength is approximately 1.7 MPa, which is comparable to the experimental results. Specifically, at a compression pressure of approximately 110 MPa, the tablet tensile strength is also approximately 1.7 MPa which is sufficient for commercial scale processing including tablet coating. However, there is a discrepancy between the predicted tensile strength and experimental results at higher compression pressures because of higher Ibu concentrations (Figure 1C and Figure 3). Therefore, this digital tool and compaction simulator provided valuable insights for optimizing formulation strategies and enabled identification of critical process parameters and their settings. The subsequent production on the R&D press yielded tablets whose critical quality attributes were within the targeted design criteria (Figure 3). This study demonstrated that the integrated approach of use of algorithm-based tool and compaction simulator could significantly help in design and development of robust pharmaceutical tablets.

Conclusion: The integration of digital formulation tools, compaction simulation, and specialized R&D pressing proved to be an effective strategy for optimizing tablet formulations. This approach not only achieved the desired critical quality attributes but also streamlined the development process, reducing time and costs. The study underscores the value of combining digital tools with experimental techniques to achieve superior pharmaceutical products. Future research will explore the applicability of this workflow to a wider range of formulations and known problem areas in the tablet design and development space.

Acknowledgements: There are no known conflicts of interest or other disclaimers.

Figure 1 Predicted processability of the co-processed and ibu blend using algorithm-based tool: A) at 20% drug loading and B) 30% drug loading and C) Tabletability Profile at 30% drug loading

Figure 2 Tabletability profile of Ibu tablets using compaction simulator

Figure 3: The compaction profile of a KORSCH XL100 R & D rotary press simulated on the STYLONE Evo compaction simulator. The pre-compression, main compression, and ejection forces are illustrated in the lower punch force trace.