Unstable

Ostwald ripening is the phenomena in which smaller particles in solution dissolve and deposit on larger particles in order to reach a more thermodynamically stable state wherein the surface to area ratio is minimized.

Ostwald ripening occurs because molecules on the surface of particles are more energetically unstable than those within. Therefore the unstable surface molecules often go into solution shrinking the particle over time and increasing the number of free molecules in solution (see Figure A below). When the solution is supersaturated with the molecules of the shrinking particles those free molecules will redeposit on the larger particles. Thus small particles decrease in size until they disappear and large particles grow even larger. This shrinking and growing of particles will result in a larger mean diameter of a particle size distribution (PSD). Ostwald ripening is often found in water-in-oil emulsions where oil molecules will diffuse through the aqueous phase and join larger oil droplets. Over time, this causes emulsion instability and eventually phase separation. When Ostwald ripening occurs in emulsions such as injectable lipid emulsions the results can be deadly. Large particles greater than 5 microns can cause embolisms in blood vessels. Therefore the United States Pharmacopeia has developed several procedures, USPand USPfor maintaining emulsion drug safety by requiring that the mean diameter and the volume of particles greater than 5 microns in the large-droplet tail be determined. This can be done using dynamic light scattering (DLS) and single particle optical sensing (SPOS) techniques.

Figure A. Ostwald ripening