Utilising Solubility Modelling to Reduce the R&D Timeline

Reducing the time drugs take to get to market is a key focus for a pharmaceutical industry facing the expiry of patents on blockbuster products and the subsequent influx of generics.

Poor solubility is one of the ever-present factors delaying drug development and it would appear current industry conditions have led pharmaceutical companies to step up investment to combat this.

Indeed, improving solubility is seen as a way of reformulating products currently on the market which have little time left before their patent expires- a situation being faced by some of the world's major drug developers.

Solubility modelling to reduce the R&D timeline

Solubility modelling using AspenTech's aspenONE Process Development for Pharmaceuticals software is what GSK, AstraZeneca, and according to the company, a number of other major pharma players, are hoping will reduce their research and development (R&D) timeline.

Using the software, companies are said to better understand the solubility of chemical entities, allowing them to in turn better identify risks.

Quickly identifying the solubility of a chemical entity enables R&D efforts to be focused on those presenting the biggest likelihood of success – saving both time and money.

AspenTech also claims this allows clinical trials to be conducted earlier, as predictive modelling allows for the efficient design of optimised manufacturing and purification processes.

Finally, it said the modelling reduces the costs of goods and supply disruptions by allowing "informed design" of the final manufacturing processes to produce less waste and a higher yield.

Stephen Carino, investigator – solid form sciences group at GSK, commented: "In our high-throughput screening workflow, we have utilized NRTL-SAC in Aspen Properties to predict the equilibrium solubility of the drug in single- and multi-component solvent systems.

"The predicted solubility values are used in selecting an appropriate set of solvent systems that are explicitly unique for each of the crystallisation modes."

The software also includes 'Quality by Design' capabilities, which allow companies to deal with changing regulatory requirements.

Looking to CROs

It's not only pharmaceutical companies looking to enhance their improving solubility capabilities; contract research organisations (CRO) have also been investing and expanding into this increasingly important area.

Molecular Profiles, a CRO based in Nottingham, UK, recently named solubility as one of the key hurdles developers face when taking their drugs from the pre-clinical phase to trials. The comments came at the same time as it announced its intentions to expand its early development phase offerings, outsourcing-pharma.com reported.

Particle Sciences Inc, based in Pennsylvania, recently inked a deal with SoluBest, which will see the company become the only CRO in the United States to offer SoluBest's Solumer system.

The technology allows the use of GRAS polymers to create drug/polymer complexes, which in turn increase solubility and bioavailability. As it can be adapted for a large number of molecules, the technology is said to be attractive to both new chemical entities and existing products.

Meanwhile, Bend Research, a contract manufacturing organisation, expanded the hot melt extrusion technology in its facilities, to boost the delivery of low-solubility drugs.

The company is already well versed in the uses of spray dried dispersion technologies, which along with hot-melt extrusion, is design to boost the oral absorption of drugs. It first introduced hot-melt extrusion into its facilities in 2002, and the addition of specialised suites for high potency pharmaceutical compounds will allow it to better transform the formulations into suitable dosages.

Bend Research President and chief executive officer Rod Ray noted the first product the company brought to market used the technology to "develop an nnovative modified-release product based on hot-melt extrusion that made it possible for patients to take a single dose of an antibiotic rather than a multi-day regimen".

Some 40 percent of compounds currently in development were said to need solubilisation technologies to allow for oral absorption.

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