Most of peptide drugs are often delivered subcutaneously. The significant barrier in this type of peptide administration is the high concentration of formulation, which can lead to self-assembly and aggregation. These phenomena can negatively impact the bioavailability, manufacturing, and injectability of the peptide drug. This study investigated the self-assembly behavior of Lanreotide acetate at high concentration in water using Hydroxypropyl β- Cyclodextrins (HPβCyD) to mitigate the self-assembly and enhance release rate during subcutaneous administration. Our finding demonstrated that the lanreotide/ HPβCyD inclusion complex effectively prevents aromatic-aromatic interactions of lanreotide, thereby controlling self-assembly. This complexation also alters the viscosity behavior of lanreotide from non-Newtonian under low shear rates to Newtonian solution. Furthermore, the lanreotide/ HPβCyD inclusion complex reduces interactions with hyaluronic acid in the subcutaneous environment, leading to significant improvement in the release rate of lanreotide acetate at high concentrations (above 3% w/w in water).
Percentage of drug release of lanreotide from ESCAR system over 7 hours for different amounts of drug at the same dose with and without the presence of HPβCyD.
Negar Jafari, Camille Addison, Hao Luo, Michael J. Hageman (2024) Hydroxypropyl β Cyclodextrins Effects on Self-Assembly of Cyclic Peptide, Lanreotide Acetate, in Water and Subsequent Release rate from an in vitro Emulator of Subcutaneous Delivery. Journal of Pharmaceutical Sciences
https://doi.org/10.1016/j.xphs.2024.11.018