Influence of emulsifier concentration on partition behavior and chemical stability of betamethasone dipropionate in emulsion gels

The partitioning of active pharmaceutical ingredients (API) in emulsions is influenced by various factors, such as composition of the phases, emulsifier type and concentration, and temperature. Therefore, the chemical stability of the API can be influenced by its partitioning into the aqueous phase as degradation is typically facilitated in water. With increasing emulsifier concentration from 0.15% to 5.0%, more betamethasone dipropionate (BDP) was solubilized in polysorbate 80 micelles leading to a small, but increased fraction of BDP exposed to the aqueous phase along with preferential partitioning of BDP to the aqueous phase and thus increased degradation. Similarly, by enhancing solubility and partitioning to the aqueous phase, the addition of polyethylene glycol 400 also led to increased BDP degradation. Due to pH dependent degradation of BDP, increasing emulsifier concentrations resulted in a more pronounced degradation of BDP at pH 8, which is beyond the stability optimum, whereas at pH 5 the API was sufficiently stable and no differences in concentration were detected within 12 weeks even under accelerated conditions. No significant differences were seen with the varying emulsifier concentrations regarding ex vivo skin penetration.