Improved initial burst of estradiol organogel as long-term in situ drug delivery implant: formulation, in vitro and in vivo characterization

Abstract

Objective: The present investigation was aimed at optimizing of estradiol (E2) loaded l-amino acid derivatives organogel formulations resulting in improved the high initial release problems and sustained release of E2.

Methods: The visco-elastic properties of blank organogels were measured by rheometer. The E2 organogel formulations were optimized using a central composite design. Also, the effect of gelator structure and composition of the gel formulations on release behavior (in vitro and in vivo) had been studied.

Results: The change of the gelator structure could affect significantly the stiffness of the implants. The release behavior of gel without N-Methyl-2-pyrrolidinone (NMP) was controlled by gel corrosion only. While the drug release of the gel with NMP was controlled by both corrosion and diffusion. The high initial release problems of the organogels were improved by optimizing the formulations. The system consisting by N-Lauroyl l-lysine methyl ester (LLM) derivative in the oil indicated the lowest initial drug release, showed a much lower blood drug level and maintained a steady state for nearly 1 month.

Conclusion: Organogels based on l-lysine methyl ester derivative were ideal carriers for long-term parenteral administration of E2.

Keywords::

• Estradiol
• in situ organogel
• in vitro release
• formulation optimization
• in vivo release