The importance of pre-compression pressure and dwell time to mitigate tablet capping problems.
Solving Tablet Capping Issues
Capping is a term used to describe the detachment of a cross-sectional fragment from the tablet face, which usually occurs just after ejection of the tablet from the die. The damage to tablets by capping will invariably lead to production batch rejection. For a registered product, changing the formulation is not the preferred option to resolve such issues. Moreover, for a high-dose product, there are limits to formulation changes and the final solution may not fully resolve the capping problem.
A possible alternative to ameliorate capping is to use a specially designed rotary tablet press that employs an air compensator at the pre-compression stage: the pre-compression force, in conjunction with an extended dwell time, can be modified prior to the main compression event. This novel mode of pre-compression force application was investigated using a GEA rotary tablet press with air compensator on granules prepared by high shear granulation; the formulation comprised 78% acetaminophen (w/w) and 22% starch (w/w). Modification of the mode of compression force application was found to be capable of reducing or even eliminating the occurrence of tablet capping without compromising the mechanical strength of the tablets produced.
Acetaminophen-starch granules were dry blended with 1.1% magnesium stearate (w/w) and 0.16% colloidal silicon dioxide (w/w). A GEA tablet press (R190FT) with 10 mm punches was used to prepare 325 mg flat beveled tablets. Various tableting parameters were investigated and they included pre-compression pressure, pre-compression tablet thickness, main compression tablet thickness and turret speed.
Main compression pressure, dwell time and displacement values were recorded for each batch of tablets produced. Batches with less than 10% tablet capping after compression were further characterized according to the USP Pharmacopoeia methods for tablet thickness (Digimatic Micrometer, Mitotuyo, Japan), crushing strength (HT1, Sotax, Switzerland) and friability (TA20, Erweka, Germany). The number of tablets capped after the friability test was also recorded.
Results and Discussion
Tablet production from granules requires the application of a certain amount of compression force or pressure. Insufficient compression pressure will result in the failure of the granules to consolidate into coherent masses or tablets that can withstand further handling or processing. However, excessive compression pressure may result in capping or excessively hard tablets that would show unduly prolonged disintegration times. For the acetaminophen-starch formulation, it was found that tablet production required the main compression pressure to be in the range of 108–140 N/mm2. Tablets produced with a main compression pressure higher than 140 N/mm2 capped immediately after compression. By contrast, use of a low main compression pressure (<100 N/mm2) produced tablets with very low crushing strength (<25 N).
For each selected main compression pressure within the 108–140 N/mm2 range, the tablet crushing strength increased whereas the tablet friability and occurrence of capping decreased with an increase in the pre-compression pressure. Using a pre-compression pressure limit of 34 N/mm2 and a main compression pressure of 108 N/mm2, the dwell time could be altered by adjusting the pre-compression tablet thickness and turret speed. The air compensator at the pre-compression roller would move the roller upwards if the pre-compression force exceeded the pre-set limiting force, thus keeping the pre-compression pressure on the tablet constant whilst the dwell time increased accordingly.
By increasing the dwell time at the pre-compression stage, tablet crushing strength was found to increase and friability decreased (Figure 3). Plastic deformation and brittle fragmentation have been reported as deformation mechanisms for acetaminophen.1,2 An increase in dwell time extended the effective contact time that the compact was subjected to an applied force capable of causing capping, which allowed for further plastic deformation. This resulted in increased particle-particle bonding times. The subsequent application of the main compression pressure further enhanced the interaction and improved the mechanical strength of the resultant tablets.
However, without the appropriate intervention at the pre-compression stage to allow for initial tablet consolidation, the application of a high main compression pressure might cause possible elastic recovery related rupture of formed bonds, thereby creating weakened areas in the tablets and predisposing them to capping.
1. E. Doelker and E. Shotton, “The Effect of Some Binding Agents on the Mechanical Properties of Granules and Their Compression Characteristics,” Journal of Pharmacy and Pharmacology 29(4), 193–198 (1977).
2. P. Humbert-Droz, et al., “Densification Behaviour of Drugs Presenting Availability Problems,” International Journal of Pharmaceutical Technology and Product Manufacture 4(2), 29–35 (1983).