The effect of mechanical strain on properties of lubricated tablets compacted at different pressures

Abstract

A full factorial design of experiments was used to study the effect of blend shear strain on the compaction process, relative density and strength of pharmaceutical tablets. The powder blends were subjected to different shear strain levels (integral of shear rate with respect to time) using an ad hoc Couette shear cell. Tablets were compressed at different compaction forces using an instrumented compactor simulator, and compaction curves showing the force-displacement profiles during compaction were obtained. Although the die-fill blend porosity (initial porosity) and the minimum in-die tablet porosity (at maximum compaction) decreased significantly with shear strain, the final tablet porosity was surprisingly independent of shear strain. The increase in the in-die maximum compaction with shear strain was, in fact, compensated during postcompaction relaxation of the tables, which also increased significantly with shear strain. Therefore, tablet porosity alone was not sufficient to predict tablet tensile strength. A decrease in the 'work of compaction' as a function of shear strain, and an increase in the recovered elastic work was observed, which suggested weaker particle-particle bonding as the shear strain increased. For each shear strain level, the Ryskewitch Duckworth equation was a good fit to the tensile strength as a function of tablet porosity, and the obtained asymptotic tensile strength at zero porosity exhibited a 60% reduction as a function of shear strain. This was consistent with a reduced bonding efficiency as the shear strain increased.

Compaction behaviour and mechanical characteristics of chewable binary tablet mixture containing lactose (Flowlac 100) and date (Phoenix dactylifera) powders

“…Elastic energy is stored in the tablet under applied pressure during compaction process and becomes elastic deformation. The amount of stored elastic energy in the tablet depends directly on the applied force (Pawar et al, 2016). This explains the increasing amount of elastic work shown in the igure for the whole samples, especially to Flowlac 100.…”

A “Large-N” Content Uniformity Process Analytical Technology (PAT) Method for Phenytoin Sodium Tablets

“…MgSt is a hydrophobic, shear-sensitive lubricant with an agglomerated structure 44 and is known to affect critical tablet properties, depending not only on its concentration but also on the shear strain acting on the blend during manufacturing. 25,45 With an increase in blend shear during prolonged mixing, MgSt is known to deagglomerate, coat other ingredients in the blend, and hinder the contact between the solvent and the API, leading to a prolonged drug release time. [46][47][48] To increase the amount of drug released in the solution, we implemented an approach to increase the solubility of the drug.…”

“…Pawar et al and Pingali et al described the effect of 'over-lubrication' phenomenon on tablet hardness and dissolution, respectively. 18,25 Overlubrication can as well affect the performance of the tablet concentration prediction models, first via affecting the primary HPLC method, and then by "smuggling" the HPLC error into the subsequent NIR calibration model. Such effects need to be accounted for during analytical method development to obtain a robust calibration model, thus increasing the accuracy of tablet concentration prediction.…”

Scaling Tableting Processes from Compaction Simulator to Rotary Presses—Mind the Sub-Processes

“…The effect is less pronounced when the Higher paddle speeds cause a more drastic decrease in tensile strength of up to 70% between 10 and 272 min −1 paddle wheel rotation frequency for lubricated MCC (Figure 8b). This can be traced back to the higher specific energy input and by that more efficient dispersion of the MgSt particles, causing them to cover the surfaces of the excipient particles [22,36]. This lessens the bonding forces within the tablet structure as lubricants show lower bonding forces when present at the interface of particles than excipient particle contacts themselves [21].…”