An Economical Design and Processing of Lipophilic Drugs for Fast-Releasing Water Dispersible Formulations

Web Published:
5/25/2018
Description:

An Economical Design and Processing of Lipophilic Drugs for Fast-Releasing Water Dispersible Formulations

 

Princeton Docket # 18-3396-1

 

The Prud’homme group has developed a novel, economical, and scalable formulation and process to prepare nanoparticles from poorly water soluble drugs in order to improve oral bioavailability and dissolution rate of lipophilic drugs where convention methods (i.e., milling) are not adequate.

 

As a proof of concept, the team has demonstrated that nanoparticles of the poorly water-soluble, Biopharmaceutics Classification System class II drug Clofazimine can be prepared with optimal drug dissolution rate and enhancement. Instead of expensive copolymers, the formulation utilizes affordable amphiphilic stabilizers, including hypromellose acetate succinate (HPMCAS), lecithin, and zein. This is the first demonstration that a cost-effective cellulosic polymer can be used to produce nanoparticles. Encapsulation efficiencies of over 92% were demonstrated, as well as remarkably improved dissolution rate, and Clofazimine supersaturation levels up to 90 times the equilibrium solubility. The nanoparticle are assembled via flash nanoprecipitation (FNP) process, which is a continuous process that is similar to existing industrial processes, has been shown to be compatible for other formulations, and is currently being scaled up to an industrially relevant production size and rate. This invention enables and improves BCS class II and III drugs for oral and topical formulations in a low-cost manner.

 

Applications

- Nanoparticle formulation of lipophilic drugs for improved bioavailability

- Aqueous dispersible formulations (i.e., oral, topical)

- Pediatric formulations

- Underserved communities (low cost)

 

 

Advantages

- Improved bio availability (i.e., surface area)

- Reduction in size compared to convention method (i.e., milling)

- Simple, low cost, and natural formulation (amphiphilic stabilizers)

- Economical, scalable, and continuous process (flash nanoprecipitation, spray drying)

 

Publication

Zhang et al. Design and Solidification of Fast-Releasing Clofazimine Nanoparticles for Treatment of Cryptosporidiosis. Molecular Pharmaceutics, 2017, 14, 3480-3488. Doi: 10.1021/acs.molpharmaceut.7b00521

 

Intellectual Property & Development Status

Patent protection is pending. Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.

 

Proof of concept Clofazimine nanoparticles were prepared with affordable amphiphilic stabilizers, including hypromellose acetate succinate (HPMCAS), lecithin, and zein. Encapsulation efficiencies of over 92%, remarkably improved dissolution rate, and Clofazimine supersaturation levels up to 90 times the equilibrium solubility were demonstrated. The process is currently being scaled up to industrially relevant scale.

 

 

The Inventors

 

Robert K. Prud’homme is a Professor of Chemical and Biological Engineering and the Director of the Program in Engineering Biology at Princeton University. His research focuses on how weak forces at the molecular level determine macroscopic properties at larger length scales. A major focus of his lab’s research is on using self-assembly to construct nanoparticles for drug delivery and imaging. His work is highly interdisciplinary; many of the projects involve joint advisors and collaborations with researchers at NIH, Argonne National Labs, CNRS in France, and major corporations.

 

Kurt Ristroph is a doctoral candidate in the department of Chemical and Biological Engineering. He was awarded National Science Foundation Graduate Research Fellowship and his research focuses on polymeric nanoparticles for improved drug bioavailability, drug targeting, imaging, mucus penetration, and antimicrobial peptide delivery.

 

Simon McManus is a postdoctoral researcher in Prof. Prud’homme’s lab. Prof. McManus’ has involved engineering nanoparticles and bioconjugates for multiple applications, including microscopy, cell-specific delivery of imaging and therapeutic agents, controlled therapeutic release, and single molecule imaging of enzymes in complex environments. He received his Ph.D. from McMaster University in Canada.

 

Yingyue (Joanna) Zhang is a postdoctoral researcher in Prof. Prud’homme’s lab. Her expertise is in organic chemistry and materials science, specifically in the design, synthesis, and characterization of novel biomaterials with intrinsic bioactivity (e.g., antimicrobial, anti-atherosclerotic activity) and/or as delivery vehicles. She received her Ph.D. from Rutgers University.

 

Hoang (Jack) Lu was a doctoral student in Prof. Prud’homme’s lab.

 

Contacts:

 

Linda Jan

Princeton University Office of Technology Licensing • (609) 258-3653 • ljan@princeton.edu

 

Laurie Tzodikov

Princeton University Office of Technology Licensing • (609) 258-7256 • tzodikov@princeton.edu

 

 

Patent Information:
For Information, Contact:
Tony Williams
Associate Director
Princeton University
609-259-3769
anthonyw@Princeton.edu
Inventors:
Jie Feng
Kurt Ristroph
Hoang Lu
Yingyue Zhang
Simon Mcmanus
Robert Prud'homme
Keywords: