Impact breakage of pharmaceutical tablets

Abstract

Tablets are the most common solid dosage form of pharmaceutical active ingredients due to their ease of use. Their dissolution behaviour depends on the particle size distribution and physicochemical properties of the formulation, and the compression process, which need to be optimised for producing consistently robust tablets, as weaker tablets are often prone to breakage during production, transport and end use. Tablet strength is typically determined by diametric compression and friability tests. The former gives rise to propagation of a crack on a plane along the compression axis, whilst the latter, carried out in a rotating drum, incurs surface damage and produces chips and debris. These tests produce different measures of strength, neither of which have been correlated with mechanical properties that are accountable for breakage, i.e. hardness, elastic modulus and fracture toughness. We propose a new method based on single tablet impact testing, following the work of Ghadiri and Zhang, 2002, who analysed particle damage by propagation of sub-surface lateral cracks and identified the fundamental form accountable for impact surface damage to be a lumped parameter related to hardness and fracture toughness. Microindentation, carried out separately, to determine fracture toughness led to complete failure of the tablets, hence an unreliable measurement of fracture toughness and no correlation with the experimental trend. In addition, by assuming the fracture toughness to be proportional to the square root of Young's modulus, the indentation measurements do not correlate well with the impact breakage. The discrepancy between the impact and indentation methods is expected to be due to mechanical property variation across the tablet surface, and with strain rate. The impact method is a more suitable test to describe tablet propensity for attrition as it directly represents the failure mode tablets may experience during processing under well-defined conditions. In contrast, the friability test subjects tablets to a similar breakage mechanism but under less well-defined conditions, whilst the compression test represents a different failure mode that is not representative of stresses incurred during processing.

Drug-eluting biodegradable metals and metal-ceramic composites: High strength and delayed drug release

“…Young’s modulus of pure Fe ranges between 187 and 214 GPa [42]. While that of VH has not been reported, it can be roughly estimated from the values of different organic pharmaceutical excipients such as starch and microcrystalline cellulose that are <10 GPa [43–45]. Such a ~20-fold difference in the elastic behavior between Fe and VH particles initiates stress concentrations in the mechanically weak drug phase during the CS.…”

Exploring the Regimes of Particle Behavior upon Impact via the Discrete Element Method

“…Experimental studies have been conducted to investigate the impact process [ 7 , 8 , 9 ]. However, it is experimentally difficult to obtain accurate information during the impact process due to the short impact duration and (often) small particle size.…”

Predictive Approach to Understand and Eliminate Tablet Breakage During Film Coating

“…Further, they also proposed a map of breakage modes (i.e., chipping, fragmentation) as a function of the number of impacts and impact velocity. Hare et al (12) proposed a single tablet impact test to quantify breakage of pharmaceutical tablets. Though, for the materials and test conditions examined, only attrition or chipping was observed and not fragmentation.…”