stearates and Anaphylaxis

The commercially available alpha-asarone injections (CA-ARE) were frequently found to cause severe anaphylactic reactions by the solubilizer contained in the formulation such as polysorbate 80 and propylene glycol. This study aimed to develop a new ARE injection using Kolliphor HS 15 as solubilizing agent (HS 15-ARE) by the dissolution method to resolve its poor solubility problem and reduce the anaphylaxis of CA-AREs caused by Polysorbate 80. The HS 15-ARE micelle showed a homogeneous round shape with the mean particle size of around 13.73 ± 0.02 nm, polydisperse index (PDI) of 0.19 ± 0.01 and solubilizing efficiency of 95.7% ± 2.4%. In vitro and in vivo studies showed that HS 15-ARE is a stable injection presenting the same pharmacokinetic profile with CA-ARE. Moreover, improved therapeutic effect was observed for HS 15-ARE in treating asthma compared to CA-ARE (p < 0.05) with no anaphylactic reactions observed. These results demonstrate that the new formulation of ARE (HS 15-ARE) has a great potential for replacing CA-AREs injections.

Topics: Allylbenzene Derivatives; Anaphylaxis; Animals; Anisoles; Anti-Asthmatic Agents; Asthma; Biological Availability; Cells, Cultured; Chemistry, Pharmaceutical; Disease Models, Animal; Drug Stability; Erythrocytes; Guinea Pigs; Hemolysis; Histamine; Injections, Intravenous; Male; Molecular Structure; Particle Size; Polyethylene Glycols; Rats, Wistar; Sheep; Solvents; Stearates; Surface Properties; Tissue Distribution