In-die evaluation of capping tendency of pharmaceutical tablets using force-displacement curve and stress relaxation parameter.

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.