Figure 1: Grafted polymers, such as polyethylene glycol with polyvinyl alcohol, provide flexibility and reduce spray-coat
time. (IMAGES ARE COURTESY OF BASF.)
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Improving polymers to reduce time, energy, and material is thus an important research area for coating formulators. BASF's
instant-release coating material is a chemically new polymer (as opposed to a new mixture or a new coprocessed polymer) made
of well-known polyethylene glycol (PEG) and polyvinyl alcohol (PVA) covalently bonded as a graft polymer, in which the sidechains
of PVA are chemically bonded to a PEG backbone ("Kollicoat IR," see Figure 1). "Because PEG is part of the polymer and because
it is chemically bound to PVA, it cannot migrate to the core nor escape the surface, and remains an extremely flexible film
for all types of tablets," says Folttmann. Kollicoat IR can be diluted to concentration of up to 30%, so the spray process
requires less water and a shorter period of time. As Folttmann observes, the challenge, as with many new excipients, is that
companies are reluctant to try a formulation that has not been reviewed by regulators or monographed in a pharmacopeia. This
year, Kollicoat IR received a draft monograph in PharmEuropa, which is expected to become final in the next year. (Visit the online exclusive article regarding the International Pharmaceutical Excipients Council's new efforts to reduce regulation hurdles for new excipients).
A statistical strategy.
When ISP entered the pharmaceutical coating segment of the industry in 2005, it set out to apply a statistical design of
experiment (DOE) to create databases that would facilitate the design of coating formulations and to ascertain the ideal processing
conditions for a given platform. "This approach has not been exploited to a high degree," says Stuart Porter, senior science
fellow of film coating technology at ISP. "When you look at FDA's quality-by-design inititiatives, clearly using a statisitical
DOE is one of the preferred approaches to creating the knowledge about the product. We have taken that same approach and created
knowledge about our component of that product, which is the coating system."
The key variables of the database are the various properties of the coating systems, including mechanical strength, flexibility,
adhesion, disintegration, dissolution, film roughness or smoothness, gloss, and cost. All responses are measured for each
formulation in the DOE and the database is created as the ratio of ingredients and the types of ingredients in the formulation
are manipulated. The database allows minimum values to be set in one area that needs to be achieved and how much the formulation
can change to maintain those minimum values while improving the value in a different characteristic that is also important.
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