One would be hard pressed to find an industry more risk averse or slow to change than the pharmaceutical industry often, for very good reason. Certainly, pharmaceutical blister packaging is a part of pharmas conservative culture, and has its own anecdotal lessons as to the consequences of risk and change.
|Progressive manufacturers are going beyond traditional pass/fail stability testing for barrier packaging and using tools such as Finite Element Analysis (FEA), which simulates barriers achieved by certain cavity geometries and barrier materials. The above simulation illustrates poorly-formed barriers in terms of thickness and permeability, the result of poor cavity geometry.|
However, there is a need for change. Not only have FDA and other global regulatory agencies called for a new risk-based manufacturing philosophy, but the marketplace is demanding materials with extremely effective barrier properties, as well as new packaging technologies.
Given the trend to use highly sensitive active pharmaceutical ingredients (API) and excipients in drug formulation, and the need to keep packaging off the critical path during the drug approval process, there is a growing need for extreme barriers, or packaging materials with increasingly high barrier properties. Such packaging will also be needed for tomorrows drug delivery systems.
But several challenges must be addressed if these materials are ever to be used routinely in pharmaceutical packaging: the need for technological change, growing demand for extreme barrier properties, and the tension between risk management and risk avoidance. This article will focus on solutions to these challenges, which have already been developed in other industries and now await implementation in pharmaceutical packaging.
Such solutions will need to be science-based and transparent. The future of barrier packaging demands nonproprietary technologies with open standards that assist rapid adoption and risk management. The question is whether the drug industry will embrace this demand, and reap the rewards that come with it.
Extreme barrier packaging
One can often best see the future of a technology or marketplace by examining its cutting edge. One can only understand extreme barrier packaging by understanding materials, machinery and tooling.
As noted above, pharmaceutical blister packaging today generally relies on well-known, well-proven solutions. In extreme barrier packaging, this traditionally means either the 50 µm (2 mil) Aclar structures originally developed for the U.S. market, or three-ply CFF structures originally developed in the European market.
However, users are demanding ever more extreme barriers, especially against moisture.
Three distinct trends drive this demand for more barrier, and will become even more important in the future:
- The growing importance of drug delivery systems;
- The tendency to develop APIs that are highly sensitive to moisture and oxygen;
- Use of super disintegrants such as sodium starch glycolate, which are becoming more important in formulation. These materials are increasingly being used in generic drug manufacturing, to help achieve desired dissolution curves and enhance bioavailability. Unlike traditional excipients, these materials require packaging materials with a much higher moisture barrier.
Until now, this demand for packaging with improved barrier properties has been met mainly by enhancing existing products, or combining materials. Each of the four traditional forming material technologies (CFF, PCTFE, COC, and PVdC) is available in new forms that address the growing demand for extreme barrier properties.
- CFF/Alu Alu: New four- and five-layer structures reduce any risk of delamination and pin-hole, and enhance stiffness and processing speed.
- ACLAR/PCTFE: Films are now available up to 100 µm or 4 mils thick, doubling the barrier offered in the traditional 50 µm or 2-mil structures.
- TOPAS/COC: New combinations of COC with PVdC are pushing barriers obtainable with these structures into barrier ranges formerly available only from CFF/Alu Alu or Aclar/PCTFE.
- PVdC: Solvay is working on a new product with several of its converters that it says significantly enhances the barrier obtained from a given gram coating weight.
In the future, extreme barrier packaging materials will most likely further segment depending on how barrier is achieved. The two current barrier alternatives, metallic (aluminum) or polymeric (PCTFE, COC or PVdC), will each continue to follow their own paths.
In metals (CFF), expect to see a focus on:
- Structure enhancement: Here, the first question will be: which polymeric film, if any, will best optimize aluminums ability to form optimal cavity geometry without stress fractures, delamination, or pin holes? The second question will be how to increase processing speed.
- Aluminum enhancement: In the future, manufacturers will routinely evaluate the ideal gauge of the aluminum substrate, and use metallurgical advances to optimize the aluminum structure.