Evaluation of tablet punch configuration on mitigating capping by a quality by design approach.

Capping is a common problem in the manufacture of some types of tablets and unless resolved, the tableting process cannot proceed. Hence, all factors that can help to lessen the likelihood of capping without unnecessarily reduce turret speed and/or compaction force would be tenable. This study investigated the influence of tablet punch configuration on mitigation of tablet capping. Tablets were prepared from high-dose paracetamol-potato starch granules in a rotary tablet press with flat face plain (FFP), flat face bevel edge (FFBE) and flat face radius edge (FFRE) punch configurations. The directly compressible (DC) fillers tested were microcrystalline cellulose (MCC), pre-gelatinised starch (PGS) and lactose. Design of experiments (DoE), a tool of quality by design (QbD) paradigm, was used and the interaction of input variables (compression force, tablet punch configuration and DC filler) affecting the response factors (tablet hardness and capping rating) were evaluated. FFP punches were able to mitigate capping best. FFRE punches showed more potential than FFBE punches at alleviating capping in a particular compression force range, without the limitations of the FFP punches that produce cylindrical tablets that were more friable. Incorporation of PGS in the tablet formulation was observed to be more efficient at mitigating capping than the other DC fillers when FFBE and FFRE punches were used. Overall, this study serves as a model for prospective product development based on the QbD framework and the optimal use of compaction tools.

Tablet compression tooling - Impact of punch face edge modification.

The influence of punch face edge geometry modification on tablet compression and the properties of the resultant tablets produced on a rotary press were investigated. The results revealed that tablets produced from the punches with radius edge face geometry consistently displayed better physical quality; higher tensile strength and lower capping tendency. Modification of the angled edge of the bevel face to the curved edge of the radius face, enabled deeper punch penetration in the die cavity during the compression cycle, bringing about greater compact densification. Improved die fill packing increased interparticulate bond formation and helped to dissipate destructive elasticity within the compact, consequently reduced tablet expansion during the decompression phase. The positive impact of punch face edge modification was also more noticeable at a higher turret speed. The application of the precompression force along with dwell time extension amplified the tableting performance of radius edge punch face design to a greater extent when compared to bevel edge punch face design. This could be attributed to the enhanced packing efficiency at both precompression and main compression stages.

Influence of the Punch Head Design on the Physical Quality of Tablets Produced in a Rotary Press.

This study aims to investigate the influence of tablet punch head design on compaction and the resultant tablet mechanical properties. Tablets were prepared using flat-face punches with different head flat and head radius configurations, on a rotary tablet press with compression rolls of different diameters. The results showed that tablets produced using punches with head flats consistently displayed higher tensile strengths and lower capping tendencies. Exclusion of the head flat in the punch head geometry caused the compacts to undergo a state of continual deformation during the compaction cycle, possibly with increasing elasticity without the opportunity for more prolonged stress relaxation. Extension of head flat diameter produced small increments in dwell time and this could bring about significant improvements to the tablet mechanical quality. Changes to the punch head radius were found only to affect the compression profiles marginally, but this only produced insignificant differences in the tablet mechanical properties. A smaller compression roll allowed greater plastic flow during the dwell phase, but this was insufficient to effectively counteract the adverse effects due to increased strain rate during the consolidation phase, leading to deterioration of tablet mechanical quality.

Direct microneedle array fabrication off a photomask to deliver collagen through skin.

PURPOSE: To fabricate microneedle arrays directly off a photomask using a simple photolithographical approach and evaluate their potential for delivering collagen. METHODS: A simple photolithographical approach was developed by using photomask consisting of embedded micro-lenses that govern microneedle geometry in a mould free process. Microneedle length was controlled by use of simple glass scaffolds as well as addition of backing layer. The fabricated arrays were tested for their mechanical properties by using a force gauge as well as insertion into human skin with trypan blue staining. Microneedle arrays were then evaluated for the delivery of fluorescent collagen, which was evaluated using a confocal laser scanning microscope. RESULTS: Microneedles with sharp tips ranging between 41.5 ± 8.4 µm and 71.6 ± 13.7 µm as well as of two different lengths of 1336 ± 193 µm and 957 ± 171 µm were fabricated by using the photomasks. The microneedles were robust and resisted fracture forces up to 25 N. They were also shown to penetrate cadaver human skin samples with ease; especially microneedle arrays with shorter length of 957 µm penetrated up to 72% of needles. The needles were shown to enhance permeation of collagen through cadaver rat skin, as compared to passive diffusion of collagen. CONCLUSIONS: A simple and mould free approach of fabricating polymeric microneedle array is proposed. The fabricated microneedle arrays enhance collagen permeation through skin.