(342d) A Model for Reliable Prediction of Tabletability of Mixtures from Those of Individual Components

There is a pressing need in the pharmaceutical industry for developing a tablet more quickly while using less active pharmaceutical ingredients (API). The empirical approaches that heavily depend on the use of Design of Experiments (DOE) cannot meet this need. Instead, a materials science-based approach to enable fast and material-sparing tablet formulation development is highly desired. In this context, the ability to predict the compression behaviors of a mixture from that of the individual components and the composition of the mixture is extremely useful.¹ In this presentation, I will describe an approach for successfully predicting tabletability of mixtures consisted of common pharmaceutical excipients and APIs.

Tabletability data was generated using a compaction simulator (Styl’One Evolution, MedelPharm, Beynost, France) simulating a Korsch XL100 compression cycle at 20 rpm with a 10 MPa precompression step. The main compaction pressure varied between 25 and 500 MPa. Round, flat-faced (6 - 11.28 mm in diameter) punches were used for all compaction. External lubrication (magnesium stearate spray, Styl’One MIST) was used on the die wall and punch tips before each compression. Tablets were broken with a texture analyzer, and tensile strength was calculated using the breaking force along with tablet dimensions following a standard process.

The first step of the prediction exercise involves quantifying tabletability data (tensile strength versus main compaction pressure) of individual powders with the Vreeman-Sun equation.² Nonlinear regression of tabletability data using the Vreeman-Sun equation leads to three fitted parameters (P), 𝜎_max, 𝛼, and 𝛽. to completely describe tabletability. This set of tabletability parameters of any two powders were used to predict a set of parameters of a mixture between the two powders using the power mixing law based on composition (C), i.e., P_1,2=P₁^C1P₂^C2.

The tabletability of a large number of binary mixtures for several pairs of powders exhibiting a wide range of mechanical properties and tabletability were successfully predicted. Validity of this approach was also shown for ternary and five-component systems, suggesting robustness and general applicability of this modeling approach.

Acknowledgments

This work was supported by the Center for Integrated Materials Science and Engineering for Pharmaceutical Products (CIMSEPP), which is funded by the National Science Foundation (grant IIP-2137264). Contributions from Gerrit Vreeman, Vedant Bhagali, Aakash Hasabnis, and Zijian Wang are greatly appreciated.

References

1. Ramaswamy, C. M., Varma, Y. B. G. & Venkateswarlu, D. Compaction of mixtures of materials. Chem. Eng. J. 1, 168–171 (1970).
2. Vreeman, G. & Sun, C. C. A powder tabletability equation. Powder Technol. 408, 117709 (2022).