Hi Alan, this many times can be a challenging part during drug substance synthesis. In my experience what has proven to be the most successful, is to have a co-solvent (mixture of solvents) if your material is not soluble in a single solvent system. Another option, which is very uncommon, would be to adjust the pH of the solvent system provided your materials won't degrade under the given pH conditions.
Hi, With regards to drug substance solubility, you can use heat and pressure to allow the solids to dissolve, which can then be pumped into the CM system.
Also you can pump a slurry through a heat exchanger to raise the temperature and achieving the required solubility, possibly under pressure. This limits the time spent by the materials at elevated temperature.
You can also attempt your chemistry in the slurry phase, we have been successful running even photochemistry as a slurry.
When looking at fixed bed hydrogenation, we do require all solids to be dissolved. We can often run the process more dilute than would normally be used during the analogous batch process, and simply remove the excess solvent after the process for immediate re-cycling back into the process.
The use of solubilizers and stabilizers in the formulation, together with some processes like producing solid dispersions by melt extrusion or spray dry techniques are ways to deal practically with the issue of poor soluble APIs. In our group at Rutgers, we are actually working with two methodologies (impregnation poorly soluble APIs in porous carriers and melt coating with only 5-10% of a surfactant) that proved to be excellent methods with some advantages over melt extrusion and spray dry. We have some patents and publications validating the processes for those interested to get more information.
Alan Steven @ on
What are the best strategies for overcoming poor solubility for materials related to the drug substance synthesis as part of solution processing?
Rohit Lokhande @ on
Hi Alan, this many times can be a challenging part during drug substance synthesis. In my experience what has proven to be the most successful, is to have a co-solvent (mixture of solvents) if your material is not soluble in a single solvent system. Another option, which is very uncommon, would be to adjust the pH of the solvent system provided your materials won't degrade under the given pH conditions.
Oliver Tames @ on
Hi, With regards to drug substance solubility, you can use heat and pressure to allow the solids to dissolve, which can then be pumped into the CM system.
Also you can pump a slurry through a heat exchanger to raise the temperature and achieving the required solubility, possibly under pressure. This limits the time spent by the materials at elevated temperature.
You can also attempt your chemistry in the slurry phase, we have been successful running even photochemistry as a slurry.
When looking at fixed bed hydrogenation, we do require all solids to be dissolved. We can often run the process more dilute than would normally be used during the analogous batch process, and simply remove the excess solvent after the process for immediate re-cycling back into the process.
Gerardo Callegari @ on
The use of solubilizers and stabilizers in the formulation, together with some processes like producing solid dispersions by melt extrusion or spray dry techniques are ways to deal practically with the issue of poor soluble APIs. In our group at Rutgers, we are actually working with two methodologies (impregnation poorly soluble APIs in porous carriers and melt coating with only 5-10% of a surfactant) that proved to be excellent methods with some advantages over melt extrusion and spray dry. We have some patents and publications validating the processes for those interested to get more information.