Maximizing Bioavailability and Expediting Time-to-Market for Poorly Soluble Drug Candidates

Poorly soluble candidates now account for 60 percent of drugs in the pipeline, and as technologies become more complex, the figure continues to increase.

Pharmaceutical companies are now stepping up investment in the technologies which will boost bioavailability, expedite time to market and ultimately boost revenues at a time when blockbuster drugs can no longer be relied upon to bring in cash and more funding needs to be pumped into pipeline.

Eli Lilly and Merck have both signed deals with Bend Research in the past six months for access to proprietary spray-dried dispersion (SDD). SDD involves dissolving drug and polymer in an organic solvent before spray drying the solution.

Conditions are set so that the solvent quickly evaporates from the droplets, before phase separation or crystallisation.

Bend claims to have formulated several hundred compounds as SDDs for in vivo testing. A further 50 drug compounds have been formulated as SDDs and manufactured as candidates for all three phases of clinical trials.

Under the deal with Eli Lilly, Bend will make available its SDD technology for candidates with low aqueous solubility and other drug development technologies.

Rod Ray, chief executive officer of Bend Research, said: "We believe this collaboration will add significant value to Lilly’s research efforts and help them advance their compounds more quickly and efficiently."

Academic institutions are also looking to use nanotechnology for drug delivery to boost bioavailability, while also controlling drug release and reducing harmful side effects.

Yissum Research Development Company, the technology transfer unit from the Hebrew University of Jerusalem, last year applied a novel nanotechnology platform to the anti-cancer drug Docetaxel.

Successful pre-clinical data showed the delivery platform was capable of instigating controlled drug release and increased bioavailability of orally administered lipophilic drugs. The drugs have proved a challenge as they are metabolised and expelled by the intestine.

When the drug is embedded within the novel microparticles, biovailailability in rodents increased 10 to 20 fold that other methods of delivery. 
 
Yaacov Michlin, cheief executive of Yissum, explained: "Docetaxel is used for the treatment of a variety of cancers, and is currently administered as a high dose infusion every three weeks, resulting in side effects that could be quite severe.

"Patients in need of this drug will thus greatly benefit from the ability to receive the drug in lower doses using an oral route."
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University of Strathclyde researchers also assess the potential for nanoparticles in delivering drugs to organ transplant patients. Cyclosporine helps prevent the body from rejecting the organ, but can lead to kidney and liver damage.

Leader of the research Professor Ravi Kumar, of the Strathclyde Institute of Pharmacy and Biomedical Sciences, explained that currently the formulations uses a castor oil-based vehicle as the drug is poorly soluble in water, but this can be toxic.

"By entrapping CsA in nanoparticles, we aimed to match the maximum concentration of the most potent formulation of the drug in market. In tests, we were able to strike a balance between strength, efficacy and safety and were able to make a marked increase in the drug’s bioavailability- the level of the drug which becomes active in the system.

"We were also able to reduce the toxic effects on the kidneys by slow release of the nanoparticles, which brought the drug gradually to its maximum concentration," he explained.

The researchers are now assessing the possibility of using the platform for the delivery of arthritis therapies.

A strong drug pipeline is becoming ever more highly prized as new era of personalised medicine and novel drugs dawns. Maximising bioavailability of these poorly soluble compounds is a priority, and one which companies cannot afford to ignore.
 

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