Development and Commercialization of a Novel Modified Release Tablet Technology - Pharmaceutical Technology

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Development and Commercialization of a Novel Modified Release Tablet Technology
GlaxoSmithKline recently developed a novel technology for the formulation of modified-release tablets. Commercialized as DiffCORE, the technology combines the use of apertures that are mechanically drilled into functional film-coated tablets, with traditional polymer matrices that control the mechanism of core erosion and diffusion. The authors describe the route from development to commercialization of this modified-release approach.

Pharmaceutical Technology
Volume 36, Issue 12

How did the technology become commercialized?

There were several aspects that required alignment for this technology to mature. The most fundamental was the initial drive or need to use a technology. Without this, there was little interest in investing potentially large sums of money with the risk of no return. The second was having compounds to work on, otherwise the resources associated with the technology are not just non-value adding but costly in a budget constrained environment. Using development compounds, by necessity, to drive a technology development ties the two processes intimately together in terms of risk—both the chance of the process not being technically deliverable for specific milestones, and the potential for a compound not progressing reducing the commitment on the technology side. The final aspect was that there was a clear strategic intent on developing commercial platforms that delivered rapid development on a wide range of active compounds.

This technology was well-placed with regards to commercialization as there was a genuine need, strong sponsorship, and was simple to apply in development. The ability to manually drill apertures on low numbers of tablets or caplets allowed for very quick in vitro proof of concept (PoC), typically under a week including analysis, enabling rapid development programs.

Once PoC had been proven, the technology program accelerated in line with the compound. Having a manual low-volume manufacturing method does not enable a technology to be used to manufacture clinical supplies for Phase IIb or Phase III, let alone commercial production. Therefore, post PoC development, a prototype automated machine had to be proven and validated at the same pace as the compound needs.

The final and perhaps the most costly step in establishing a commercial technology was to develop the prototype into a true manufacturing process (equipment, facility, and ways of working) with the full support of the commercial organization. The ability to complete the development process on a commercial scale at a manufacturing site requires great organization and cooperation between the development and manufacturing teams as both are working against aggressive timelines. The requirements for establishing a new technology from a business and industry perspective were broad, and encompassed well-documented validation and regulatory requirements. As this was a novel technology, education of external parties, such as FDA, was required to increase understanding of the technology to enable appropriate assessment of the control measures. This whole process enabled GSK to cover the entire gamut of scales in manufacturing with the benefit of having a scale-independent technology from development to commercialization.

Isn't this just a modified osmotic pump?

At first glance, this MR approach has some similarity to osmotic pump tablets (5) in that they both have apertures in their coatings, but the aperture sizes are significantly larger in this approach with an aperture on each face of the tablet (6). The larger apertures ensure that no hydrostatic pressures build up, and that release is controlled by the exposed surface area, which is typical of polymer systems, and not osmotic pumps (7).

There are two main control mechanisms:

  • Polymer type and concentration, which dictate the erosion rate of the tablet core and subsequent diffusion rate of the API.
  • The surface area of the core exposed for release of the API, which is controlled by (a) the aperture size in the gastric region, and by (b) the core geometry in the intestinal region.

What API types and doses can the approach be used for?

Due to the nature of this technology, there has been a perceived level of risk associated with "being the first" so the initial uptake has been with compounds that have had a number of challenges or difficulties in developing a more traditional MR dose form. However, in summary, a range of compounds across the Biopharmaceutics Classification System (BCS) have been tested and shown great success. More recently, the launch of a commercial product has helped to reduce this perceived risk and embed the technology within GSK.

Three late-phase compounds have shown the breadth of the technology. Two products utilized doses as low as 2 mg, and have proven to be consistent and reproducible in their delivery while a high-dose product, at 1000 mg, has been kept to a single daily tablet to aid patient compliance without having to use unnecessary levels of polymers.


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