Unlock Drug

Potential

Lipid Q&A

of research going on in the industry to

overcome the challenges in bringing
poorly soluble drugs to the market.

Improving drug development

success rates

Selecting a suitable drug-delivery

approach for these challenging NCEs
depends on various parameters,
explains Praveen Raheja, associate
director, Formulations, at Dr Reddys
CPS, for example, the drug solubility,
chemical composition, melting point,
absorption site, physical characteristics,
pharmacokinetic behavior, dose, route of
administration, and intended therapeutic
concentration, to name a few. An analysis
of all these parameters is required to
determine the most appropriate method
of drug delivery, he says.
According to Marshall Crew, PhD,
vice-president, Global PDS Scientific
Excellence, Patheon, there are two
aspects that must be understood in a
comprehensive way before proceeding
toward the best solubilization
technologythe drug molecule and
the target product profile. The dosage
form, dosage, and other requirements
for the drug product must be taken
into consideration, along with the
molecular properties and profile of the
API, he says. Modern pre-formulation
approaches begin by understanding
the target product attribute space,
5 | July 2016 | PharmTech/Patheon eBook

Solving Poor
Solubility

and leverage modeling to more

fully characterize and understand
the molecule. Crew explains that
this approach enables solubilization
formulation scientists to know the starting
point and direction of the process from
the earliest stage to formulation design
and optimization.
Once the drug product requirements
have been understood and the API
characterized, solubilization technologies
can be screened to identify the best fit for
the particular drug and desired outcome,
Crew adds. After the technology has
been identified, the next step is to
conduct experiments involving a range of
excipient/polymer models in combination
with the drug. Crew advocates the use of
computational screening, which allows a
greater number of options to be explored
more efficiently, thereby increasing the
likelihood of identifying the best approach.
Dan Dobry, vice-president, Bend
Research, a division of Capsugel Dosage
Form Solutions, also recommends a
mechanistic, model-based approach.
Simple modeling and characterization
tools can relate physicochemical aspects
of the compound and therapy to potential
delivery challenges, he notes. The
models are often not quantitative in
early development, but give context to
experiments, in vitro and in vivo, to help
shape the problem statement and pair
the right delivery technology.