The Effects of Fillers and Binders on the Accuracy of Tablet Subdivision

Abstract

The effects of excipients on the accuracy of tablet subdivision are severely underinvestigated. In this study, placebo tablets were prepared using a combined mixture design of fillers and binders to evaluate the effect of these excipients on subdivision accuracy. The responses assessed were mass loss, mass variation, tablet fragmentation, and increased friability. Dicalcium phosphate dihydrate (DCP) gave rise to more uniform and denser tablets than microcrystalline cellulose (MCC), thus resulting in greater subdivision accuracy. The binder type, hydroxypropylcellulose (HPC) or polyvinylpyrrolidone (PVP), did not affect the subdivision of DCP tablets. On the contrary, the structural similarity between HPC and MCC led to improved subdivision accuracy for MCC tablets. A less accurate subdivision was observed in tablets prepared with a DCP-MCC combination; this finding could be attributed to irregular binder distribution in this matrix. An optimized response was built using desirability analysis. This study helps to illuminate the relationship between fillers and binders to guide formulation scientists in the development of tablets with better subdivision performance.

Tablet Scoring: Current Practice, Fundamentals, and Knowledge Gaps

“…Tablets manufactured with MCC and HPC showed better accuracy when partitioned, as opposed to those manufactured with a diluent that contained an equal amount of MCC and DCP. This was attributed to the similar structures of HPC and MCC, which facilitate the tablets partition [149].…”

“…Controlling the processing parameters during high shear granulation is important as there are several factors that can influence the tablet properties, and subsequently impact tablet partitioning. While excipient particle sizes and excipients of structural similarities should be controlled, their effect becomes less important since a granulation solution will be used to densify the granulation [149]. The orifice of the spray nozzle used to conduct the granulation plays a crucial role as the droplet size can impact granulation densification [150].…”

“…Binder selection and concentration should be considered carefully as the viscosity of the binder solution can impact granule properties [152]. If adequate amount of binder is used, the tablets are less brittle; which can then circumvent tablet weight loss after partitioning, tablet fragmentation, tablet halves weight variation and reduce the % friability [149]. The impeller speed should also be optimized, as dispersion of the granulation solution would dictate the granulation endpoint [153].…”

“…For example, lactose should not be used in combination with amine bases or amine salts [167] as the resulting tablet can be subjected to discoloration and degradations [167]. In a study that was conducted using placebo tablets manufactured using MCC and DCP, it was noted that MCC produced less uniform and less dense tablets compared to those produced with DCP [149]. Tablets manufactured with elastic diluents such as starch and DCP are more amenable to partitioning that those manufactured with plastic materials such as microcrystalline cellulose and lactose [168].…”

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

“…The effervescent extrudates containing paracetamol were developed according to a combined mixture design planned for using the polymeric matrix (HPMC and PVPVA) and the disintegrating agent (PTK and LDF) as input variables (Table 1) [23][24][25]. The responses were chosen considering important parameters for the production and use of effervescent drug products, i.e., moisture content, disintegration time, compressibility, and drug solubilization.…”