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Bend Research, Pfizer seek to improve drug bioavailability
September 2007
by Randall C Willis  |  Email the author
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BEND, Ore.—For medicinal chemists, a major source of frustration is watching a good drug candidate fail because it cannot be delivered effectively in vivo. In many cases, this is the result of formulation problems, with the compound having either low solubility at pharmacological concentrations or poor absorption or metabolism characteristics (bioavailability).
"Many of the newer compounds are experiencing bioavailability issues, and it is expected that this will continue because of the complexity of these products," says Mary Anne Crandall, senior pharmaceutical analyst for Kalorama Information. "That has created barriers for pharma companies and caused failures of developmental products in trials."
To address this challenge, Bend Research and Pfizer developed a new delivery technology—spray-dried dispersions (SDDs)—that Bend recently announced it will make available to other organizations looking to improve the clinical effectiveness of experimental compounds. "For numerous pharmacological reasons, many active compounds have poor aqueous solubility," says Dr. Marshall Crew, Bend's VP of Chemical and Biological Sciences. "A large percentage of these compounds are poorly absorbed when dosed orally."
As he goes on to explain, these otherwise-effective compounds are typically pulled out of the development cycle, further weakening already dwindling drug pipelines. Bend and Pfizer found a way around this problem, however, by generating homogeneous solid dispersions of drugs in a polymer matrix that improves the bioavailability profile of a candidate by increasing both the dissolution rate and the free-drug concentration significantly over the more typical crystalline forms of therapeutic candidates.
"The SDD technology expands the druggable chemical space currently limited by traditional oral dosing constraints, such as Lipinski's 'Rule of Fives'," Crew explains  "The SDDs provide a solid, amorphous drug substance that is easily formulated as a tablet, capsule, or powder."
Pfizer has applied the technology to more than 200 preclinical compounds and 17 clinical compounds, seeing bioavailability improvements in the range of 10-fold over crystalline forms, according to company literature.
With an eye to potential licensing opportunities beyond their own doors, however, the two companies decided to open the SDD technology to other research organizations, with Bend performing the initial leg work in the form of short-term feasibility studies. From its perspective, Bend's focus is on leveraging the SDD technology to assist in licensing compounds into Pfizer, and being compensated for success.
"Our primary interest is in compounds that have reached in vivo studies and, preferably, Phase I," Crew says. "In most cases, this will mean that the compounds will come from small discovery companies that are strategically receptive to licensing to Pfizer."
Kalorama's Crandall sees significant opportunities in this effort for Pfizer. "I see this as a good strategic move by creating a means of increasing its pipeline availability, gaining an edge over the competition, and increasing prospects for development of products through other avenues without significant financial commitment until the product is further along in the clinical process."
"Pfizer has always understood the value of partnering in order to overcome the highly complex scientific challenges of drug discovery," said Pfizer R&D President John LaMattina in a prepared statement. "This new initiative shows how we can share scientific expertise to help discover new medicines for patients in need."
 
 
Code: E090702

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