In-Die Evaluation of Capping Tendency of Pharmaceutical Tablets Using Force-Displacement Curve and Stress Relaxation Parameter

Abstract

A novel in-die evaluation method of tablet capping tendency was proposed based on a force-displacement curve and stress relaxation parameter in a tableting process. In our previous study (Chem. Pharm. Bull., 59, 2011, Nakamura et al.), the phase diagram consisting of elastic recovery energy (E e ) and plastic deformation energy (E p ) of compressed powder, named as the E e -E p diagram, was proposed. However, it was found that capping tendency of tablets prepared by double-compression with multi-component powder formulations cannot be discriminated using the E e -E p diagram. To improve the capping discrimination ability, we here proposed a novel corrected phase diagram consisting of the E e and an interparticle bonding parameter E b (t), named as the E e -E b (t) diagram. The E b (t) was proposed as a new parameter expressing strength of the interparticle bonding formed by the stress relaxation inside compressed powder. The E b (t) was defined as a product of the E p and the stress relaxation parameter Y(t), estimated from the force-displacement curve and the stress relaxation test. The capping discrimination ability of the diagrams was evaluated using a hierarchical-clustering analysis. The results exhibited that the capping tendency could be clearly discriminated using the proposed E e -E b (t) diagram at the double-compression and the multi-component powder formulations, as compared to the E e -E p diagram. This proposed diagram can be used for screening of the powder formulations to avoid the capping.Key words tableting; capping; stress relaxation; force-displacement curve; hierarchical-clustering analysis When pharmaceutical powders are compressed into tablets, cracking or lamination sometimes occurs inside the tablets. This phenomenon is well known as capping. The capping is one of the most common tableting troubles. Although many efforts have been made to overcome the trouble, the capping has still been an unsolved issue. Thus, a methodology to evaluate and avoid the capping has been a strong interest in pharmaceutical industries.Generally, capping tendency can be evaluated by out-ofdie or in-die evaluation methods. In the out-of-die evaluation methods the capping tendency is evaluated after ejection of the tablet from a die, whereas in the in-die evaluation methods the capping tendency is evaluated during preparation of the tablet.As an out-of-die evaluation method of the capping tendency, visual inspection after a friability test 1) is widely accepted. An indentation fracture test 2) has been proposed as an out-of-die evaluation method, in which the capping tendency was evaluated by making a small indentation fracture on the tablet. An X-ray microtomography, 3,4) by which cracks inside a tablet can be directly visualized noninvasively, has also been employed as an out-of-die evaluation method. However, the out-of-die evaluation methods are cumbersome, because they need to handle tablets after their preparation.By contrast, in-die evaluation methods can evaluate the capping tendency using data monitored...

On the Links Between Elastic Constants and Effective Elastic Behavior of Pharmaceutical Compacts: Importance of Poisson’s Ratio and Use of Bulk Modulus

“…The elastic properties of pharmaceutical powders and compacts are of great interest to understand the complex phenomena that occur during the tableting process. Adverse phenomena like capping were linked to the elastic properties of the compact that can be evidenced during the unloading part of compaction cycle and the ejection . The elastic properties are also involved in the problems of delamination of multilayers compacts …”

“…Adverse phenomena like capping were linked to the elastic properties of the compact that can be evidenced during the unloading part of compaction cycle and the ejection. [1][2][3] The elastic properties are also involved in the problems of delamination of multilayers compacts. 4,5 To model the elastic behavior of the compacts, linear elasticity based on Hook's law has been used for a long time in the pharmaceutical field.…”

Characterization of Tableting Speed-Dependent Deformation Properties of Active Pharmaceutical Ingredients in Powder Mixtures Using Out-of-Die Method

“…The mechanism of capping is related to several factors, such as the powder properties and the manufacturing conditions. For example, the powder properties related to the occurrence of capping, stress relaxation, 1,2) elastic recovery, 3) and residual die-wall pressure have been reported. 4,5) In particular, high-pressure compaction and high tableting speeds are more susceptible to these effects.…”

“…The relevance of this method to capping properties has also been reported. 1) Heckel analysis is used to evaluate deformation characteristics related to the compression. 15) This method is based on the response of powder porosity to pressure during compaction.…”

Numerical evaluation of the capping tendency of microcrystalline cellulose tablets during a diametrical compression test

“…Therefore, several novel prediction methods of the capping tendency have been investigated. Nakamura et al (2011Nakamura et al ( , 2012 proposed that the capping tendency could be evaluated using the energy of elastic recovery and plastic deformation. Kuppuswamy et al (2001) http://dx.doi.org/10.1016/j.ijpharm.2015.07.029 0378-5173/© 2015 Elsevier B.V. All rights reserved.…”