Variations in polyethylene glycol brands and their influence on the preparation process of hydrogel microspheres

Hydrogel microspheres, e.g. for the use as protein carriers, can be prepared without the use of organic solvents via an emulsified aqueous two phase system (ATPS) that is based on two immiscible polymer solutions. The type and concentration of the polymers can affect the ATPS and finally the distribution of incorporated drugs between the aqueous phases. For the preparation of hydrogel microspheres based on hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA), hydroxyethyl starch-methacrylate (HES-MA), and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)6MA), polyethylene glycol 12,000 (PEG 12,000) was used as second polymer. The particle size distribution and encapsulation efficiency of the microspheres depended dramatically on the type of PEG 12,000 that was used in the second phase of the ATPS. Analysis of different PEG 12,000 brands by various methods revealed differences in the salt composition and molecular weight distribution of the polymers which can explain the results from the production process. The results illustrate that the range of product specifications may not always be tight enough to avoid variability in pharmaceutical processes like the preparation of hydrogel microspheres by an aqueous-two-phase preparation process.