What are the common challenges involved in the formulation, manufacturing, and testing of scored tablets?
It is challenging for drug manufacturers to identify a robust formula that creates correct hardness and satisfies quality
requirements for splitting. Being able to screen rapidly is key in order to test many formula, formats and options. The challenge
here is to perform tests quickly and efficiently.
How easy is it for manufacturers of traditional tablets to ensure that the dosage units of subdivided tablets fall within
the accepted criteria of USP, EP, and other guidance documents?
Traditionally, tablet scores have been applied more as an aesthetic/marketing feature than with the expectation of any functional
purpose. With the advent of regulatory changes begun first in Europe and now also proposed in the US, functional scoring of
tablets has taken on a new meaning and placed additional requirements on manufacturers wishing to market tablets with a score.
Achieving the requirements currently set out for functionally scored tablets is no simple matter for tablet manufacturers
because tablet design, processes, and expected testing of the finished dosage form have all taken on new complexities. Data
now must prove that the score results in a fraction of the whole dosage form that meets the same requirements as the intact
or unscored tablet. This requirement has placed additional testing requirements on those manufacturers who wish to have functionally
scored tablets. Issues such as segment content uniformity, friability of the tablet segments, in vitro dissolution performance and stability of the fractured tablet segments must all be investigated and documented as part of
The content uniformity is even more critical with a dose becoming smaller and an already higher weight variance due to splitting
tablets. This variance adds more pressure in scale-up and formulation, requiring more robust processes.
Medelpharm for example did some experiments for a customer with progressive-shape tooling where we examined the ideal shape
(angle of indent), as well as single- or double-side scoring and the benefits of using a "narrow waist" tablet. Producing
small batches at production speed, we were able to predict which upper and lower pairs of punches and die selection produced
the best tablets for meeting regulatory requirements. At the same time, we tested the efficiency of shaped dies and of different
punch tips to find the best compromise between quality acceptance and tooling costs.
Meeting requirements is tricky, however, since quality guidelines take into account human action in breaking tablets. And,
as we all know, the regulatory-defined process for breaking a tablet is rarely followed in everyday life.
To ensure tablets can be split evenly with good dosage content uniformity, what factors do tablet manufacturers need to take
As always, monitoring and knowing key critical parameters are crucial to quality. During research and development of the compression
stage, it is important to use final production tools (punches), use similar compression parameters than during production
(e.g., forces, compression cycle/speed and pre-compression), and use similar weight regulation systems to control filling
and weight homogeneity. Different compression forces or speeds between research and development and production will create
different hardness and density inside the tablets, which will impact dissolution and breakage.
Powder flow in the feeding systems, and inside the tablet during compression, is another parameter that should be measured.
High-speed production press simulators can monitor these parameters.