Effect of geometrical features on the capping behavior of biconvex tablets
Abstract
Capping is a common industrial issue during the manufacturing of pharmaceutical tablets. It is influenced by both process and formulation parameters. In this work, a systematic study of the influence of the geometrical features of biconvex tablets on capping occurrence was performed on a model formulation using a design of experiment. Capping was characterized by the pressure at which half of the produced tablets were capped. Influence of the tablet geometry was assessed by varying three parameters: the diameter (D), the band thickness (W) and the ratio between the radius of curvature (R) and the diameter, i.e. R/D. Results showed that having a large diameter, a low band thickness and a high curvature (i.e. a low R/D) favored capping occurrence. Moreover, the effects are not independent as cross-effect were detected. Finally, even for homothetic tablets (i.e. same R/D and W/D) it is shown that a large diameter increases capping occurrence. These results could be used in the future as a guideline for punch selection during tablet development.
Introduction
Capping is a common industrial issue during the manufacturing of pharmaceutical tablets which is known for more than a century (Wood, 1906). In the case of biconvex tablets, it corresponds to the failure of one or both cups of the tablet (Alderborn, 2001). It differs from another classical tablet defect, lamination, which corresponds to a failure of the tablet with a failure plan passing through the tablet band (Alderborn, 2001; Mazel and Tchoreloff, 2021). There is a large literature dealing with capping problems, nevertheless, it is sometimes to be taken with caution as in some papers, defects called capping in fact correspond to lamination as in (Tanino et al., 1995, Osamura et al., 2018).
The occurrence of capping during the manufacturing of tablets results from a complex interaction between the product properties and the process parameters. Concerning the properties of the formulations that may influence the occurrence of capping there is no general consensus in the literature. As an example, a high residual die wall pressure is often cited as a factor that favors the occurrence of capping (Hiestand et al., 1977, Sugimori et al., 1989, Sugimori and Kawashima, 1997) but other authors presented inverse trends (Paul and Sun, 2017). Parameters like low plastic energy during the cycle have also be found to correlate well with capping occurrence (Nakamura et al., 2012, Meynard et al., 2022a). Nevertheless, there is for the moment no definitive approach to predict capping based on the formulation properties and capping prediction remains a complex challenge (Meynard et al., 2022a).
Concerning the process parameters, some of them are clearly identified as factors that promote capping. The first one is the applied pressure as it is well-known that capping increases along with the compaction pressure (Ritter and Sucker, 1980, Akseli et al., 2014, Meynard et al., 2022b). The compaction speed is also known to have a great influence on capping (Ritter and Sucker, 1980, Garr and Rubinstein, 1991, Sarkar et al., 2015, Meynard et al., 2022b). Precompression is also an important parameter when capping occurs as it can be used to suppress it, even if the mechanism behind this mitigation is still not well understood (Mann et al., 1982, Vezin et al., 1983, Mazel and Tchoreloff, 2020).
Another important factor in the occurrence of tablet capping is the tablet shape. Nevertheless, there are not so many articles in the literature that tried to completely understand this link, especially in the case of biconvex tablets. Desai et al. studied the case of flat faced bevel edge (FFBE) and flat faced round edge tablets (FFRE) showing that FFRE led to lesser capping than FFBE. In a study on flat faced tablets, Ritter and Sucker showed that capping increased with tablet thickness (Ritter and Sucker, 1980). This is in contradiction with the results presented by Sugimori and Kawashima who wrote that capping tendency increase with the ratio between Tv (thickness of the flat tablet having the same volume as the convex faced tablet) and the band thickness of the convex faced tablet (Sugimori and Kawashima, 1997). For tablets with a constant diameter and curvature radius, this ratio decreases when the band thickness increases, meaning that increasing the band thickness should decrease the capping tendency. Using the same ratio, it can also be deducted that increasing the radius of curvature will favor tablet capping as it is generally known from the common practice (Sixsmith and Mccluskey, 1981, Sugimori and Kawashima, 1997, Gad, 2008). This was recently confirmed (Patel et al., 2023).
A biconvex tablet can be described from a geometrical point of view by 4 geometrical features as described in Figure 1: diameter (D), total thickness (T), band thickness (W) and radius of curvature (R) (Note that here the land of the tablet is neglected for the sake of simplification). Nevertheless, only three of them are independent as, for example, the total thickness can be expressed as a function of the other variables as follows:
If the land of the tablet l is taken into account, the variable D in Equation (1) must be replaced by (D-l). In order to compare punches of different sizes and shapes, instead of using R, the variable R/D is often used and the punches are generally classified as standard (R/D=1), shallow (R/D>1) or deep (R/D<1) (Bauer-Brandl, 2015). As a consequence, the geometry of the tablet can be described using the three following variables: R/D, D and W.
As only the influence of R/D seems to have been consistently studied in the literature, the aim of the present paper is to present a systematic study of the influence of these three parameters as well as their interaction on the capping behavior of a model formulation.
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Powders
The study was performed on a formulation chosen for its capping tendency. The products used were: micronized Paracetamol “Para” (Novacyl, Lyon, France), Microcrystalline cellulose “MCC” (Vivapur 12, JRS Pharma, Rosenberg, Bade-Wurtemberg, Germany), granulated lactose monohydrate “MLac” (SuperTab 30GR, DFE Pharma, Goch, Nordrhein-Westfalen, Germany), sodium crosscaramellose “CCNa” (Vivasol, JRS Pharma, Rosenberg, Bade-Wurtemberg, Germany), and magnesium stearate “MgSt”.
Vincent Mazel, Cléo Garcia, Pierre Tchoreloff, Effect of geometrical features on the capping behavior of biconvex tablets, International Journal of Pharmaceutics, 2023, 123365, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.123365.