(T1130-02-11) Impact of Material Spring Behavior on the Sticking Propensity During Tablet Manufacturing: Part 1- Single Component Pharmaceutical Systems

Purpose: The aim of the present investigation was to evaluate the impact of spring behavior of materials on their sticking tendency during the tableting operation.

Methods: Four model materials such as a predominantly plastic [Vivapur® 102 (microcrystalline cellulose)], an elastic [Starch 1500® (pregelatinized starch)], a low fragmenting [SpheroLac® 100 (α-lactose monohydrate)], and a high fragmenting [Emcompress® (Dicalcium Phosphate Dihydrate) were chosen. Helium density value was used to calculate the powder mass required for each tablet to be 0.1913 cm³. A weighed amount of these materials was poured manually and compressed at 94.86 ± 3.46 MPa compression pressure (CP) and at 500 mm/s compression speed using the Direct Simulator Presster. Tableting tools were coated externally with MgSt. The tablets were made using 10 mm flat-faced punches. The material spring behavior was evaluated by computing the material strength and the deformation properties using a continuous compression profile. The material deformation was evaluated with ‘In-die’ Heckel method [1]. The material and tablet strength during the compression and the decompression phase was evaluated with published moduli method [2]. An in-die and ‘out-of-die’ tablet expansion was computed with previously published method [3]. The sticking index was evaluated by measuring the powder’s angle of internal friction and the powder’s wall friction angle with various coupons like S7, M340, and Natoli Ultracoat using FT4 rheometer [4, 5]. Finally, a statistical qualitative and quantitative relationship between these evaluated parameters was evaluated by employing principal component analysis (PCA), and partial least square regression-1 (PLS-1), respectively. These analyses were done using Unscrambler® software. 

Results: The Heckel YPpl values of studied materials were found in the following ascending order: Vivapur® 102< Starch 1500®< SpheroLac® 100< Emcompress®. The Heckel YPel values were found in the following ascending order: Starch 1500®< Vivapur®102< SpheroLac® 100< Emcompress®. This confirmed their respective predominant material deformation behaviors. In all materials, Starch 1500® showed a high compression modulus (CM) in 5 to 20 MPa CP range, while Vivapur® 102 and Emcompress® showed low CM in the same range. The CM trend in 20 to 60 MPa range was in the following ascending order: Vivapur® 102< Starch 1500®< SpheroLac® 100< Emcompress®. A low decompression modulus (DCM) could insinuate weaker tablets strength and a high ‘in-die’ expansion and vice-a-versa. In all materials, Starch 1500® exhibited the lowest DCM. This suggests its high ‘in-die’ elastic or a spring behavior of Starch 1500® during the decompression phase. In all materials, Starch 1500® showed the highest sticking index (SI), while Emcompress® showed the lowest SI. A high SI means high material sticking propensity during the tableting operation. Qualitative PCA scores and loading plots (Figure 1) showed a positive correlation of SI with ‘in-die’ expansion, ‘out-of-die’ expansion, and decompression phase tablet porosity. This plot also revealed an opposite correlation of SI with CM, DCM, DCM to CM ratio 5 to 20 and 20 to 60 MPa, as well as with Heckel YPpl and YPel values. Similar quantitative relationships were also observed with PCR-1 models computed for SI index of respective coupons (Figure 2).

Conclusion: These results confirmed that materials forming weaker tablets along with a high spring behavior in the decompression phase (in-die’ tablet expansion) could show a high sticking tendency during the tableting operation. These studies are the first part of the broader project but certainly highlight a significant role of material spring behavior on the sticking tendency. Certainly, this material sparing approach could predict potential tablet sticking in the early phases and take respective measures rather than waiting for the late phase, where sticking problem becomes more prominent.

References: 1. Haware, R.V., I. Tho, and A. Bauer-Brandl, Application of multivariate methods to compression behavior evaluation of directly compressible materials. European Journal of Pharmaceutics and Biopharmaceutics, 2009. 72(1): p. 148-155.
2. Patel, D.B., et al., Compression–decompression modulus (CDM) – an alternative/complementary approach to Heckel’s analysis. Pharmaceutical Development and Technology, 2022. 27(7): p. 805-815.
3. Haware, R.V., I. Tho, and A. Bauer-Brandl, Evaluation of a rapid approximation method for the elastic recovery of tablets. Powder Technology, 2010. 202(1): p. 71-77.
4. Nakamura, S., et al., Predicting the Occurrence of Sticking during Tablet Production by Shear Testing of a Pharmaceutical Powder. Chem Pharm Bull (Tokyo), 2016. 64(5): p. 512-6.
5. D. Patel, K.C., R. Sedlock, R. Haware, Powder Rheology: Gateway for Tablet Sticking Insights, in Manufacturing Chemist. 2021, HPCi Media Limited: Shrewsbury, UK.

Acknowledgements: Authors do not have any conflict of interest.

Figure 1 (A) The principal component (PCA) score plot: (B) Loading plot of material strength, material deformation properties, and sticking index. The first two principal components display explain 87% data variance.

Figure 2 A representative Principal component regression (PCR-1) model for Sticking Index with M340 metal coupons. The significance of regression is determined by full cross-validation and Marten’s uncertainty test and corresponds to approximately p<0.005. Bars are 95% confidence bars. A positive (+) and negative (-) sign indicates a positive and negative impact on material’s M340 SI index.