Stable Micelle Drug Formulations

Method for producing stable, concentrated drug micelles that reduce or eliminate surfactants from drug formulations.

 

Background:

Hydrophobic drugs comprise a substantial proportion of all pharmaceutical compounds in use today.  These drugs have limited solubility in water.  There are numerous strategies for addressing solubility; however, for many compounds that are yet more difficult to dissolve, more extreme excipient strategies are required.  These frequently involve formulations formed from surfactants and non-aqueous solvents.  Non-ionic surfactants such as Cremophor EL are commonly used for parental formulations but induce negative side-effects including anaphylactic hypersensitivity and neurotoxicity.  Non-aqueous solvents have potential to cause hemolysis and in the case of oils, pulmonary micoembolisms.

 

Technology Overview:

This invention is based on the observation that diverse hydrophobic drugs can self-assemble into "frozen" drug micelles when contacted with a block-copolymer such as a Pluronic block copolymers.  Low-temperature  processing subsequently enables removal of 99.9% or all of the excipient, leaving pure "frozen" micelles that can be concentrated as desired.  The remaining Pluronic is incorporated into the micelles and keeps them dispersible  with drug:excipient ratios as high as 40:1, orders of magnitude greater than existing systems.  This approach was validated for common hydrophobic drugs formulations, such as phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel, propofol, Vitamin K, and docetaxel.

 

https://buffalo.technologypublisher.com/files/sites/6814_6819_in-part_image.jpg

Source: astrydmad, https://stock.adobe.com/uk/189530120, stock.adobe.com

 

Advantages:

  • Drug to excipient ratio 2-3 orders of magnitude greater than existing formulations
  • Scalable formulation
  • Formed only from clinically-used and GMP-available materials

 

Applications:

Formulation and delivery of hydrophobic drugs.

 

Intellectual Property Summary:

U.S. Patent 9,757,334 issued 9/12/2017.

 

Stage of Development:

 

Formulation demonstrated with propofol, Vitamin K, cyclosporine and docetaxel.

 

Licensing Status

 

Available for licensing.

 

Additional Information:

Nature Communications May 19, 2016

 

Patent Information: