IN THIS ISSUE - Drug Development & Delivery

CHOOSING THE APPROPRIATE
TECHNOLOGY
Bend Research takes an “agnostic”
approach to choosing the appropriate
solubilization technology, guided by a
number of factors, including the
compound’s physical-chemical properties,
the projected dose, the desired release
profile, and the results from numerous
formulation and process models that we
have developed throughout the past
15 years.
The goal in choosing the optimum
solubilization technology is aimed at
solving the right problem for that specific
compound. Bend Research is capitalized
for formulation development and cGMP
manufacturing for spray-drying, hot-melt
extrusion, and particle-size reduction to
support our agnostic approach.
Additionally, we can support the
formulation of self-emulsifying and lipid
formulations relying on a partner to
complete the cGMP manufacturing.
While we consider all possible
technologies as we develop formulation
approaches for poorly soluble compounds,
our experience in the formulation of more
than 500 low-solubility compounds is that
spray-drying amorphous dispersions is the
most widely applicable approach. This
process involves dissolving the compound
and a concentration-sustaining polymer in
a volatile organic solvent that is rapidly
removed in the spray dryer. This process
allows for rapid drying of the formulation
and isolation of the amorphous dispersion.
It is widely applicable in that it avoids
either melting the compound in a hot-melt
process or relying on the solubility of the
compound in a lipid vehicle.
An additional benefit is that the
spray-drying process has been scaled
down to small scales compatible with
early preclinical quantities of compound
and scaled up to the multi-ton scales
necessary for commercial manufacture.
SPRAY-DRIED DISPERSIONS:
KEY FACTORS & PROCESS
OVERVIEW
There are three key components to
obtaining a high-performing amorphous
dispersion. These are the spray-drying
process conditions, the identification of
the compound’s physical-chemical
properties, and finally, the choice of
excipients that are used in the amorphous
dispersion.
The spray-drying process is
conceptually quite simple. Initially, the
compound and a dispersion polymer are
dissolved in a volatile organic solvent
(e.g., acetone or methanol). The solution is
then introduced into the drying chamber
of a spray dryer along with heated
F I G U R E 2
nitrogen. The heated gas evaporates the
solvent, leaving a dried powder, which is
collected in a cyclone or baghouse.
Of course, the process isn’t quite that
simple. If the drying capacity of the
nitrogen is insufficient, product will be
deposited on the walls of the spray dryer,
resulting in “spray-painting” and reduction
of product yield. If the drying capacity of
the nitrogen is overdesigned, energy costs
are increased, and the risk of degrading a
thermally labile compound is increased.
However, by using best practices,
spray-drying conditions can be identified
that allow the product particles to be
maintained at low temperatures (due to
evaporative cooling as the volatile solvent
evaporates), while producing high product
yields (avoiding spray-painting of the
walls of the dryer). These best practices
for spray-drying process development
were highlighted in a 2009 publication in
the Journal of Pharmaceutical Innovation.
Drug Development & Delivery July/August 2012 Vol 12 No 6
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