(T0930-08-45) Effect of Die Taper and Precompression on Air Entrapment during Tablet Compression

Purpose: Air entrapment is a significant concern during pharmaceutical tablet manufacturing because it can severely influence tablet mechanical properties, deteriorate quality, and cause type 1 lamination.^1–3 Many factors can significantly affect the propensity of a formulation to exhibit air entrapment during tablet manufacturing, including tooling design,⁴ punch-die clearance,⁵ compression location within the die,⁶ and powder deformation characteristics.^7,8 The use of precompression and a tapered die design are widely employed to avoid such issues during manufacturing since they do not require reducing overall tablet throughput. However, a systematic comparison of the effectiveness of these methods has not been reported.
A formulation containing a plastic active pharmaceutical ingredient (API) exhibited severe lamination propensity due to air entrapment when compressed. Therefore, the goal of this study was to evaluate the effectiveness of both precompression and die taper on improving tablet mechanical properties by reducing entrapped air.

Methods: The intragranular components of the dry granulation formulation include a mixture of a model plastic API, microcrystalline cellulose, mannitol, crospovidone, colloidal silica, and magnesium stearate, while the extragranular ingredients included microcrystalline cellulose, crospovidone, colloidal silica, and magnesium stearate.
Tablets were prepared using a compaction simulator (Styl’One Evolution, MedelPharm, Beynost, France) using a displacement-controlled compression cycle simulating a Korsch XL100-TSM B rotary press at 103 rpm (20 ms dwell time, 24720 tablets/hr). Oval-shaped, 200 mg embossed tooling was used to make 600 mg tablets between compaction forces of 5 and 20 kN with either a straight bore or a tapered bore die, with and without 10% precompression. These tablets were coded, weighed, and subjected to an expedited friability test using a friabilator (Pharma Alliance Group Inc., Model F2, Santa Clarita, CA).⁹ The tablets were dropped 100 times (25 rpm for 4 min), then each tablet was weighed on an analytical balance. The friability was calculated according to Equation 1.

Friability (%)=(w_initial-w_tumbled)/w_initial * 100 (1)
Where w_initial is the initial tablet weight and w_tumbled is the tablet weight after 100 drops.

Results: Directly after compression, visual defects were observed on the tablets made using a straight bore die with and without applying a precompression step (Figure 1). However, using a tapered die resulted in relatively pristine tablets regardless of whether or not precompression was employed (Figure 1). The friability of tablets made with the straight bore die is significantly higher than those made with a tapered die, which was < 1% at compaction forces >5 kN, regardless of precompression level (Figure 2). This indicates that precompression was ineffective at alleviating tablet defects caused by air entrapment, but using a tapered die is effective. These results seem to initially parallel type 2 lamination, which occurs due to the development of shear stresses upon ejection instead of type 1 lamination (air entrapment).^3,10 However, because the defects are present on the tablet surface and not the band, air entrapment is the most likely culprit causing the defects during decompression. The combination of two possible factors may facilitate this. First, air may not easily escape if the initial clearance between the punch and die is too small, thus trapping air inside the powder and die during compression regardless of whether a precompression step was used. This may be exacerbated by the fast speeds used for compression. Second, the precompression pressures may be sufficiently high to seal trapped air within the compact, which may render precompression ineffective, and tablet defects remain. This problem can be addressed by a tapered die, which allows an easier air escape during the initial stage of compression. The lack of an effect on air entrapment by precompression when the tapered die was used may be attributed to the fact that sufficient air evacuation was achieved through the widened clearance between punch and die wall during the initial stage of compression facilitated by the tapering. Hence the addition of precompression showed no additional benefits

Conclusion: The effects of tapered die and precompression to eliminate air entrapment issues in a formulation were evaluated under high-speed tableting conditions. Surprisingly, precompression had no impact on the deleterious effects of air entrapment, while using a tapered die was highly effective at eliminating surface defects and reducing tablet friability. The use of a tapered die alone was as effective as the combination of precompression and the tapered die, suggesting that air escape during the initial stage of powder compression is the key mechanism for attaining improved tablet quality for this formulation. This example shows that air entrapment issues may be encountered even for roller compacted granules, and common strategies for overcoming such issues require careful assessment early in development.

References: 1. Mazel, V., Busignies, V., Diarra, H. & Tchoreloff, P. Lamination of pharmaceutical tablets due to air entrapment: Direct visualization and influence of the compact thickness. Int. J. Pharm. 478, 702–704 (2015).
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7. Akseli, I., Stecuła, A., He, X. & Ladyzhynsky, N. Quantitative correlation of the effect of process conditions on the capping tendencies of tablet formulations. J. Pharm. Sci. 103, 1652–1663 (2014).
8. Akseli, I., Ladyzhynsky, N., Katz, J. & He, X. Development of predictive tools to assess capping tendency of tablet formulations. Powder Technol. 236, 139–148 (2013).
9. Osei-Yeboah, F. & Sun, C. C. Validation and applications of an expedited tablet friability method. Int. J. Pharm. 484, 146–155 (2015).
10. Long, W. M. Radial Pressures in Powder Compaction. Powder Metall. 3, 73–86 (1960).

Acknowledgments: Funding from the National Science Foundation through grant number IIP- 1919037 is gratefully acknowledged for partially supporting G.V. CCS thanks the National Science Foundation for support through the Industry University Collaborative Research Center grant IIP-2137264, Center for Integrated Materials Science and Engineering for Pharmaceutical Products (CIMSEPP).

Tablet visual appearance directly after compression under different tooling and precompression conditions.



Friability of tablets produced under conditions of different combinations of tooling design and precompression. The dashed horizontal line indicates maximal acceptable tablet friability (1%).