A sustainable future for spray drying
John Baumann and Michael Morgan , R & D directors at Lonza Small Molecules , present a technology advance in spray drying for pharmaceuticals
For some time now , poor water solubility has been a challenge for a significant fraction of New Chemical Entities in the pharmaceutical pipeline . This problem has only grown in recent years as new drug targets and modalities have driven medicinal chemists to target lower-solubility drug molecules . This has led to a need to apply enabling formulation technology to many drugs molecules in order to achieve adequate oral bioavailability . Of several bioavailabilityenhancing formulation approaches for such molecules , amorphous solid dispersions ( ASDs ) are one of the most common and effective . Here , the crystalline API is converted to a high-energy amorphous form and molecularly mixed with a functional polymer to confer stability and improve performance . Spray drying ( Figure 1 ) is the most commonly used technique to manufacture ASDs . First , the API and polymer are dissolved within a solution tank . The solution is then pumped at high pressure into an atomiser at the top of a spray dryer , where the atomised solution droplets meet a heated nitrogen gas stream . The solvent evaporates , leaving solid particles trapped in the amorphous phase , which are then collected in a cyclone .
While spray drying is a fairly mature and often-used process , it has its drawbacks . Large quantities of organic solvent are typically necessary , giving it a big environmental footprint . In addition , it is often difficult to identify a suitable organic solvent to dissolve the drug that is also amenable to the process . Many APIs are so poorly soluble in water and many organic solvents that they are informally referred to as ‘ brick dust ’. For these , more solvent is required due to the low solubility , which leads to long processing times with the associated increased energy costs . This low overall solids concentration in the spray adds further technical challenges for product collection efficiency , and can lead to poor flow and inadequate compressibility when it is made into tablets .
Switching solvents
Attempts to overcome poor organic solubility often involve use of less desirable solvents , particularly dichloromethane ( DCM ) and tetrahydrofuran ( THF ). Both pose health and environmental concerns . DCM is an ozone-depleting greenhouse gas and the rise in highly insoluble APIs entering development means that its usage has grown significantly in recent years . It is also a chlorinated solvent that is thought to have neurotoxicological effects in both humans and animals . THF , while not chlorinated and much less toxic , has a tendency to form peroxides , which can be a significant safety problem when processing at a large scale . Finding alternative solvent approaches , would
22 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981