Recent advances
PharmTech:
On an industry level, can you highlight recent advances in HME with respect to improvements in the manufacturing process
and its application to different types of APIs?
Bend Research:
HME is a technology that has been widely used in pharmaceutical and nonpharmaceutical industries for decades. Recent advances
in HME include efforts to reduce processing temperatures by including plasticizers and reduce the residence time of the compound
and polymer during processing. Numerous research groups are looking at nonvolatile plasticizers, such as vitamin E or triethyl
citrate, to reduce processing temperatures. Others have reported the use of volatile excipients, such as supercritical carbon
dioxide, to avoid decreases in the final dispersion's glass-transition temperature that occur with traditional plasticizers.
There have also been recent reports of the use of equipment that has significantly reduced residence time. Professor McGinity's
research group at the University of Texas has developed a process called Kinetisol to make amorphous dispersions. It is based
on equipment that was developed to recycle plastics, which can reduce the residence time of the API and polymer at processing
temperatures from minutes to tens of seconds.
PharmTech:
Can you highlight recent industry advances in spray drying with respect to improvements in the manufacturing process and
its application to different types of APIs?
Bend Research:
Although spray drying is a well-established process, innovations in formulation approaches and process equipment are occurring.
In formulation, there is an increasing need for a third component in the dispersions to help deliver challenging compounds
aimed at novel biological targets. Often, a surfactant is added to help increase the dissolution rate or dispersion-particle
wetting or to provide an alternate micelle source to enhance drug solubility in vivo.
Equipment advances include novel spray-dryer and cyclone designs to collect the dispersion particles more efficiently. This
is especially significant for particle-engineering applications such as inhalation, which requires the manufacture and collection
of particles with a narrow particle-size distribution for delivery to the lung.
As part of the effort to formulate compounds with low solubility in organic solvents, Bend Research has developed a "hot process,"
which allows a drug suspension to be heated to high temperatures—often well above the ambient-pressure boiling point of the
solvent—in a heat exchanger to dissolve the drug immediately before it is introduced into the spray dryer. This decreases
solvent use and can result in a more scalable process.
PharmTech:
One specific technology of Bend Research is the spray-dried nanoadsorbate technology. Can you explain this technology and
how it differs from conventional spray drying?
Bend Research:
Two physical situations are dose-limiting when formulating amorphous dispersions: low dissolution rates for compounds that
are highly lipophilic and recrystallization for compounds that have high melting temperatures. To formulate highly lipophilic
compounds, we have developed the spray-dried nanoadsorbate technology as an extension of spray-dried dispersions. This technology
is based on spray drying an amorphous dispersion onto a high-surface-area inorganic support such as Cab-O-Sil (fumed silica).
The increased surface area promotes faster dissolution of the dispersion and is particularly well suited for highly lipophilic
compounds (e.g., compounds that have LogP values greater than 6 to 7). Similarly, to formulate compounds with high melting
temperatures, we have developed a technology that is based on intentionally recrystallizing the compounds in the dispersion
polymer in nanometer-sized domains. This formulation type also is a high-energy form of the API that contains a concentration-enhancing
polymer.
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