Tim Bee. Senior Director, Pharmaceuticals, at ISP Pharmaceuticals.
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Polymeric excipients have been used in the pharma industry for years. Historically, their greatest use has been as binders
and disintegrants to improve the physical properties of granules and tablets. More recently, polymers have been used to control
and modify drug release. This trend started with sustained release technologies, with the gelling properties of polymers being
used to slow drug release by diffusion through a hydrogel matrix. Enteric polymers target the release of a drug at different
points in the gastrointestinal tract using polymers that are soluble at different pH ranges.
The use of polymers to control and modify drug release is expected to continue to grow as formulators understand how to better
use the functional properties and benefits of polymers to enhance the performance of their drug products. This increased use
of the functional benefits of polymers will allow more NCEs to be brought to market and support the development of more line‑extension
products of existing APIs.
Solid dispersion technology
Most recently, polymers are being used to form solid dispersions of poorly soluble drugs to enhance their solubility and bioavailability.
Polymers play two roles in solid dispersion technology used to improve drug solubility. The first role is to enhance the physical
stability of the amorphous drug and prevent drug recrystallisation during production and storage. The second is to prevent
the drug from recrystallising in vivo.
During production and storage, the polymer can prevent the drug from crystallising through both thermodynamic and kinetic
mechanisms. In the case of thermodynamic stabilisation, there is sufficient enthalpic interaction between the polymer and
the drug for the drug to molecularly dissolve in the polymer — much like sugar dissolves in water. In the case of kinetic
stabilisation, the high‑glass transition temperature of the polymer helps to increase the glass transition temperature of
the polymer‑drug matrix, which reduces the molecular mobility of the drug, inhibiting crystal nucleation and crystal growth
in particular. Thermodynamic stabilisation is the preferred mechanism because there is no threat of recrystallisation on any
time‑scale, although kinetic stabilisation can be effective as well.
Solid dispersion technology works particularly well with APIs that have limited solubility because of high crystal lattice
energies and high melting points. Formation of the amorphous form of the drug in a solid dispersion eliminates the energy
barrier required to break down the crystal lattice structure of the drug, which is the first step in its dissolution.
Future improvements
There is still a lot to learn about solid dispersion technology; however, it provides another option in a formulator’s toolbox
to address the challenges presented by poorly soluble drugs. With self‑emulsifying systems, micronisation, nanocrystals, cyclodextrins,
surfactants, liquid‑filled soft gels and solid dispersions, formulators have multiple technologies at their disposal to formulate
poorly soluble drugs. None of these technologies is a panacea and each has its advantages and limitations, but having multiple
options means formulators are more likely to find a technology that works well for their specific API.
In the future, the biggest improvements relating to polymeric excipients will come from a better understanding of how existing
polymers perform in existing systems, as well as the advantages and limitations of the different polymers in combination with
different types of APIs in different formulations. Once this information is known, formulators will be able to combine different
polymers in new ways that bring synergistic benefits to their formulations.
