(T1030-03-20) Material Deformation or Material Hardness or Both: Tool for Predicting Tabletability Performance

Purpose: A high drug load Ibuprofen is a predominantly plastic material (1). Predominant plastic materials are generally known for producing stronger tablets (2). However, ibuprofen, being plastic deforming material, is known to form weaker tablets. Thus, the aim of the present investigation was to evaluate and predict the compression performance of ibuprofen direct compression formulation.

Methods: Ibuprofen and its formulation with Vivapur® 102 lubricated with 1% magnesium stearate in a different ratio such as 20:79:1; 30:69:1; 40:59:1; 60:39:1 were prepared. The formulations were compressed at 100 MPa using a Prester compaction emulator with 10 mm punch using a constant true volume of 0.1911 ± 0.0005 cm³. The forced-displacement data was parameterized with Heckel descriptors and newly developed compression and decompression modulus. The obtained data was evaluated with multivariate analytical tools such as principal component analysis (PCA) and partial least square regression (PLS). Finally optimized PLS model was used to predict tablet mechanical strength (TMS) of two formulations who were not the part of optimized PLS model.

Results: As expected ibuprofen exhibited an opposite correlation with Heckel values [higher plasticity] as compared to Vivapur® 102 along PC1 axis (Figure 1). However, it was not possible to produce mechanically viable tablets with 100 % ibuprofen like Vivapur® 102. Ibuprofen and Vivapur® 102 showed a respective positive and negative correlation with compression and decompression modulus. It suggests that though ibuprofen is a higher plastic than Vivapur® 102, a poor tabletability of former one could be attributed to its higher material hardness. Ibuprofen formulations Heckel and modulus values showed inverse relations with ibuprofen amount added in the formulation. These findings are further confirmed with an optimized PLS which showed positive impacts of Heckel values, and decompression modulus, while a negative impact of compression modulus on tablet mechanical strength (Figure 2). Finally, the predicted values of ibuprofen formulations from the optimized PLS model exhibited a good agreement with the measured values (Figure 3).

Conclusion: The present work demonstrated the importance of material parameterization with both material deformation and material hardness to optimize and predict the formulation performance. This is specifically important with a high drug load formulation ( < 30%) where active pharmaceutical ingredient have enough opportunity to dominate final tablet properties.

References: 1. Nakamura S, Otsuka N, Yoshino Y, Sakamoto T, Yuasa H. Predicting the Occurrence of Sticking during Tablet Production by Shear Testing of a Pharmaceutical Powder. Chem Pharm Bull (Tokyo). 2016;64(5):512-6.
2. Haware RV, Tho I, Bauer-Brandl A. Application of multivariate methods to compression behavior evaluation of directly compressible materials. European Journal of Pharmaceutics and Biopharmaceutics. 2009;72(1):148-55.

Figure 1: PCA (A) Score and (B) loading plot.

Figure 2: PLS plot correlating ibuprofen and MCC material properties with table mechanical strength.

Figure 3: Comparison of measured and predicted values of model ibuprofen formulations