(T1230-09-57) Application of X-Ray CT Scan and Material Profiling to Evaluate Tableting Performance of Kollitab™ DC 87 L

Purpose: The aim of the present investigation was to investigate X-ray Computed Tomography (CT) scanning and material profiling combination approach to gain mechanistic insights into ‘Kollitab™ DC 87 L’ compaction behavior and internal structural integrity compared to a physical blend of its components.

Methods: A model co-processed Kollitab™ DC 87 L and physical blend of its components (87% Lactose monohydrate, 9% crospovidone, 3% Kollitab® IR, and 1% sodium stearyl fumarate) with and without 20% ibuprofen (Ibu) was compressed at ~100 MPa compression force with 7 mm round D-tooling using indirect compaction simulator. A generated continuous compression profile was utilized to compute material deformation and material strength by ‘in-die’ Heckel analysis (1) and compression modulus (2) methodology. A non-destructive high-resolution X-ray computed tomography (CT) was employed to visualize an internal tablet structure of Kollitab™ DC87L and physical blend tablets with and without 20% ibuprofen. (Ibu) The CT Lab HX system was used for CT data collection of tablets using 50 kV, 160 µA and no filter. Data was collected using a 10 mm field of view (FOV), 4 sec exposure time for 2400 projections. Data were reconstructed using 2 x 2 binning mode with voxel size of 7.1 µm. Finally, dissolution performance of Ibu Kollitab™ DC87 L and Ibu Kollitab™ DC87 L components physical blend tablets were measured with USP II apparatus and 0.1 N HCl (pH 1.2) as a dissolution media. The paddle speed was 75 rpm. The temperature of dissolution media was 37 ± 0.5 ^oC.

Results: An ‘in-die’ Heckel analysis exhibited higher yield pressure (YP) of plastic deformation and elastic recovery values of Kollitab™ DC 87 L than those of its components’ physical blends (Fig. 1A and 1B). Kollitab™ DC 87 L also showed low compression modulus values in 10 to 20 MPa and 30 to 60 MPa as compared to simple physical blend of its components (Fig. 1C). These findings insinuated that co-processed Kollitab™ DC 87 L is relatively soft and undergoes extensive fragmentation than physical blend. This could be attributed to increased amorphization of major component lactose monohydrates during the co-processing step (3). Extensive fragmentation and more effective distribution of Kollicoat® IR binder in the co-processed particles increased tablet strength by enhancing the number of interparticle bonds (4). Kollitab™ DC 87 L tablets “as is (placebo)” and with 20% ibuprofen were >3 times stronger than those made with the physical blend. A strong and uniform structure of Kollitab™ DC 87 L tablets was further confirmed with X-ray CT scan. The X-ray CT scan revealed that Kollitab™ DC 87 L tablets did not possess any internal cracks while tablets made with physical blend of Kollitab™ DC 87 L flaunted several internal cracks (Fig. 2A and 2B). This correlated with higher porosity in the physically blended tablets (49.4% vs 46.2%) at the same compression force. As a results, the ibuprofen release from Kollitab™ DC 87 L tablets had less variability than that from tablets made with physical blend of Kollitab™ DC 87 L (Fig. 2C). For the dissolution study, the tablets were individually compressed to minimize the variation in tablet weight, strength, and API assay value. Ibu direct blend tablets weighed 0.1498 ± 0.0004 mg with an assay of 101.0 ± 2.94% (tablet tensile strength 1.23 ± 0.0548 MPa). Ibu Kollitab™ DC 87 L tablets weighed 0.1502 ± 0.0001528 mg with an assay of 101.46 ± 2.74% and tablet tensile strength 1.53 ± 0.0704 MPa.

Conclusion: These studies revealed that a co-processing of Kollitab™ DC 87 L components produced a soft and extensively fragmenting material with superior tableting performance than the simple physical blend. The X-ray CT scan coupled with co-processed excipient profiling approach provides a mechanistic insight into the material performance during the tableting process. This combination approach could provide a deeper understanding of the material performance from the early to late-stage development for developing robust formulations or troubleshooting of existing formulation problems.

References: 1. 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.
2. Patel DB, Patel VD, Patel Y, Sturgis JC, Sedlock R., and Haware RV. Compression–decompression modulus (CDM) – an alternative/complementary approach to Heckel’s analysis. Pharmaceutical Development and Technology. 2022;27(7):805-815.
3. Haware RV, Kancharla JP, Udupa AK, Staton S, Gupta MR, Al-Achi A, et al. Physico-Mechanical Properties of Coprocessed Excipient MicroceLac® 100 by DM(3) Approach. Pharmaceutical research. 2015;32(11):3618-3635.
4. Haware RV, Tho I, Bauer-Brandl A. Multivariate analysis of relationships between material properties, process parameters and tablet tensile strength for α-lactose monohydrates. European Journal of Pharmaceutics and Biopharmaceutics. 2009;73(3):424-31.

Acknowledgements: Authors have no conflict of interest. This work is not supported by public funding

Material profiling (A) Heckel YPpl; (B) Heckel YPel; and (C) compression moduli of Kollitab™ DC 87L and its components physical blend with and without ibuprofen

Correlation of tablet internal structure obtained from X-ray CT scan with dissolution performance (A) X-ray CT scan of Kollitab™ DC 87 L components physical blend tablet; (B) (A) X-ray CT scan of Kollitab™ DC 87 L tablet; (C) Ibuprofen release from Kollitab™ DC 87 L components physical blend tablet and Kollitab™ DC 87 L tablet (N=6).