Dow Assists Drug Delivery With Excipients And Outsourcing

By Louis Garguilo, Chief Editor, Outsourced Pharma

For over one hundred years, The Dow Chemical Company has supplied chemicals to the world. The last few years, a Dow business unit has focused intently on improving a specific area of the pharmaceutical industry: solubility, and thus bioavailability, in new and existing drugs.

Sarah Eckersley, Global R&D Director, Dow Pharma & Food Solutions (DP&FS), says her unit is becoming a vital part of the drug-delivery chain for pharmaceutical companies. She’s confident that over half the pharmaceutical companies one could name are already taking advantage of the science, technology and platform for the polymers Dow supplies as excipients.

In Dow’s advancement and supplying of these polymers, it also works hand-in-hand with outsourcing service providers. But don’t call Dow itself a provider: I tried three times, and Eckersley kindly corrected me at each attempt.

Dow Participates In The Drug Industry

With a Ph.D. in chemical engineering and 22 years at Dow in various roles, Eckersley knows her science and technologies. But I first appreciate her sales and marketing savvy. She insists Dow is not an outsourcing service provider for an important reason: “Ultimately, we are selling a product,” she says. “Yes, we are providing solutions, but at the end of the day our current offering is a polymer. And we now offer one to pharma that does a much better job of solving some difficult challenges.”

Again like a sales pro, she defines the customer’s pain point: “I’d say about 70 percent of the drug actives [active pharmaceutical ingredients or API] being developed by pharma today have bioavailability problems.”

Utilizing decades of experience with polymers and new R&D advancements to produce excipients, Dow recently announced the strengthening of its AFFINISOL™ drug solubility enhancement portfolio for spray dried dispersion (SDD) and hot melt extrusion (HME) formulations. On the SDD front, AFFINISOL™ HPMCAS (hypromellose acetate succinate) is actually a range of polymers developed in collaboration with Bend Research, a CRO, to help maintain stable solid dispersions and inhibit API crystallization. Dow says it offers enhanced polymer tailoring options to maximize solubilization performance.

AFFINISOL™ HPMC is designed for HME hypromellose, a well-recognized crystallization inhibitor whose success has been limited in HME formulations due to the narrow temperature range between thermal softening and discoloration, as well as a high melt viscosity. Dow has designed a next-generation cellulosic polymer that maintains the crystallization inhibiting properties of HPMC and can be extruded over a wide temperature range. It does this without the use of plasticizers, which can be detrimental to final drug product.

Megatrends and Market Strategy

Three years ago Dow changed the name of its Wolff Cellulosics unit to Dow Pharma & Food Solutions. “The new name coincides with a strategy we developed to concentrate on applications that were health-related, and those include both the pharma and food market segments,” says Eckersley. “These are regulated markets where high quality is demanded.”

Since that name change and new course, R&D and market activity has picked up.  Last October, the company announced the completion of a new operational facility for AFFINISOL™ HPMCAS at CDMO partner Cambrex’s Karlskoga, Sweden, site. Then earlier this year Dow informed the market it had the ability to supply solubility-enabling excipients at commercial volumes.  

I ask Eckersley whether this was catalyzed more by internal or market forces. “This was Dow driven, but I think about it as the intersection of a marketplace need with the ingenuity of our scientists and engineers. It derives from the work we do aligning with megatrends that Dow recognizes.”

These “megatrends” include aging populations and increased consumer awareness of health issues and choices, both in the West and extending to developing countries. Eckersley sees these adding up to more access and demand for drugs globally.

“Also,” she says, “many more people are living a middle-class lifestyle, and some health issues come with that, for example diabetes in India or an increase in obesity overall. We recognized there are real problems to be solved around the world. Dow sees this as a worthy place to utilize our unique knowledge and invest in solving long-term and difficult challenges.”

Outsourcing Plays A Key Role

Dow fully participates in the pharmaceutical outsourcing industry. As mentioned above, Cambrex is Dow’s polymer manufacturing partner. Given the amount of CDMOs to choose from, I ask Eckersley how they settled on this particular alliance.

“We looked for a partner with a solid reputation for making products in GMP, a track record for making polymers, and also one who could respond quickly,” she says. Regarding this third requirement, “once the opportunity space was identified, Dow set an aggressive timeline to get to market. We surveyed the CDMO landscape and Cambrex best fulfilled the requirements. We were able to quickly take the technology from our own GMP pilot plant to their manufacturing operation.”

On the R&D side, DP&FS selected Bend Research of Bend, Oregon, a company closely affiliated with Pfizer for many years and recently acquired by Capsugel of Morristown, New Jersey.

“We started that relationship about three or more years ago,” says Eckersley, “because they are recognized as the best in class in understanding spray dry dispersions used in producing drug product and intermediates for this problem of solubility enhancement. There was a unique strength and strategic fit. We had the strength in polymer development and they brought insight into how to apply those polymers to solving solubilization problems.”

Eckersley is also quick to point out that the research for Dow’s new tableting technology, METHOCEL™ DC2, which is based on methylcellulose, also relied on a CRO. “We are making an HPMC polymer that is chemically identical to what is being used today,” explains Eckersley, “with the difference that we can control the particle size and shape of that excipient powder to facilitate roller and direct compression manufacturing of tablets. We validated that at Rubicon Research of Mumbai, India.”

“So we actually utilize outsourcing providers to validate our technology on larger scale. In this case, Rubicon validated that this new version of methylcellulose flows better and affords a 60 percent improvement in manufacturing costs.”

Dow considers addressing productivity challenges as the second pain point after solubilization in the pharmaceutical industry today. “This technology is relevant for people who want to do large-scale production, for example generic manufacturers. We are effectively reducing manufacturing costs while increasing throughput,” Eckersley says. “DP&FS is finalizing the installation of a new manufacturing line in Midland, Michigan, where METHOCEL DC2 will be produced. We will offer this next‐generation HPMC excipient to the market through the DOW‐COLORCON Controlled Release Alliance,” she added.

Dow Pharma & Food Solutions, autonomous in operations but backed by the entire Dow organization, is improving the manufacture and effectiveness of new chemical entities and existing medicines for patients around the world. Eckersley says they may be introducing more services around their expertise. So while I won’t dare call DP&FS a you-know-what, it certainly is a welcome partner to the pharmaceutical industry.