Sirolimus formulation with improved pharmacokinetic properties produced by a continuous flow method

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Pharmacokinetics

Background:

• Sirolimus oral bioavailability is poor due to low dissolution, leading to variable blood levels.
• Marketed formulations (oral solution, nanocrystal tablets) improve pharmacokinetics but are complex.
• Existing approaches present challenges in production complexity and composition.

Purpose of the Study:

• To develop a simplified, scalable nanostructured Sirolimus formulation.
• To compare the physicochemical and pharmacokinetic properties of the new formulation against a marketed product.
• To explore potential applications for the novel Sirolimus formulation.

Main Methods:

• Controlled continuous flow precipitation of Sirolimus with stabilizers.
• Characterization of particle size, redispersibility, and stability.
• Comparative pharmacokinetic study in vivo after oral administration.

Main Results:

• The continuous flow method produced stable nanoparticles (<100nm) that redispersed instantly.
• The nanostructured formulation demonstrated superior stability under accelerated conditions.
• Oral administration led to faster absorption, higher exposure, and increased trough concentrations versus the marketed form.

Conclusions:

• Continuous flow precipitation offers an intensified and scalable method for producing nanostructured Sirolimus.
• The developed formulation exhibits enhanced oral bioavailability and stability.
• This approach may facilitate lower-dose oral Sirolimus products and gel-based topical systems.