Production
of Nanoparticles and Microparticles by Evaporative Precipitation
into Aqueous Solution (EPAS)
Description
Nearly half of the new chemical entities
identified by drug discovery programs are rejected as product
candidates due to poor water solubility. The safety and efficacy
profiles of many poorly water-soluble drugs on the market
are often compromised by poor or erratic bioavailability.
Simply increasing dosing to achieve effective serum levels
introduces a greater risk of toxicity
The industry has employed various strategies to improve bioavailability,
including the synthesis of more soluble derivatives, the use
of surfactants and excipients, conjugation, and reduction
in particle size by grinding and milling. These approaches
may alter the chemistry of the drug substance, introduce additional
toxicities, or fall short of the needed reduction in particle
size
Several methods have been developed in recent years to create
nanoparticles with the surface area, morphology and wetting
ability to enable rapid dissolution and better absorption.
Nanoparticle size may also be exploited for targeted delivery
to certain organs, tissues or cell types. Common techniques
for nanoparticle and microparticle production include precipitation
with a compressed fluid antisolvent (PCA) and rapid expansion
from supercritical to aqueous solution (RESAS).
EPAS is a method for preparing highly potent, rapidly dissolving
particles of poorly water-soluble drug particles. The method
comprises dissolving a drug in at least one organic solvent
to form a drug/organic mixture, atomizing the drug/organic mixture
into an aqueous solution containing stabilizers, and concurrently
rapidly evaporating the organic solvent in the presence of the
aqueous solution to form an aqueous dispersion of the drug particles
The rapid evaporation of solvent results in a very high supersaturation
and a rapid nucleation of particles. Particle growth and size
is controlled by the use of stabilizers. The resulting drug
particles are in the nanometer to micrometer size range with
meta crystallinity or an amorphous structure. The particle
size distribution is monodisperse
University of Texas at Austin investigators and their collaborators
have formulated several drugs using EPAS and have demonstrated
the desired potency, morphologies, and dissolution properties.
High concentrations of nanoparticles of intraconazole created
by EPAS have been delivered to the lungs of mice by nebulization.
Nanoparticles of intraconazole delivered by this route have
proven effective in treating Aspergillus infections.
Benefits
- Very high potency, in some cases over
90%
- Control of particle size
- Control of size distribution
- Ability to minimize particle agglomeration
- Collected at atmospheric pressure, unlike PCA
- Avoids use of superfluids common in RESAS
Market Potential/Applications
Pharmaceuticals to overcome solubility barriers for new chemical
entities (NCEs) and for product cycle management; food and
nutritionals
IP Status
One U.S. patent issued: 6,756,062
One U.S. patent application filed
Three foreign patents issued
Three foreign patent applications filed
For further information please contact:
University of Texas,
Austin, USA
Website : www.otc.utexas.edu
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