PHARMACEUTICAL NANOTECHNOLOGY
Drug particles in the nanometer size range
have unique characteristics that can lead to enhanced performance
in a variety of dosage forms. Formulated correctly, particles
in this size range are resistant to settling and can have
higher saturation solubility, rapid dissolution, and enhanced
adhesion to biological surfaces, thereby providing a rapid
onset of therapeutic action and improved bioavailability.
Scientists at Cirrus Pharmaceuticals, Inc. use nanotechnology
to approach classical and novel drug delivery applications.
We provide services for producing, formulating, and characterizing
nanoparticles for a wide array of applications including,
but not limited to, oral, pulmonary and parenteral delivery.
Applications
Oral
- Improving solubility and bioavailability of poorly soluble
drugs
- Reducing fed / fasted variability
- Reducing inter-subject variability
- Drug targeting
Pulmonary and Nasal
- Novel formulation opportunities
Parenteral
- Potential for intravenous administration of poorly soluble
drugs
- Activity screening of newly developed poorly soluble
drugs
- Drug targeting
Formulation Development
Cirrus has capabilities to generate nanoparticles
using size reduction or particle building methods. A variety
of specialized liquid milling equipment allows us to generate
dispersions of submicron particles or droplets. Conversely,
particles can be created through controlled precipitation.
The process and formulation are developed together to yield
a narrowly distributed, physically stable dispersion of primary
particles. Types of dispersions that can be developed include:
- Nanosuspensions
- Nanoemulsions
- Solid lipid nanoparticles
While suspensions are solid-in-liquid dispersions
and emulsions are liquid-in-liquid dispersions, solid lipid
nanoparticles are formed as a liquid in liquid dispersion
which is transformed to a solid-in-liquid dispersion by solidification
of the droplets. This chemically stable alternative to colloidal
drug carriers can be tailored to achieve a modulated drug
release.
Dosage form selection and formulation optimization
are aided by extensive use of statistical experimental design.
Short-term accelerated stability studies and physical stress
testing are typically employed to challenge the candidate
formulations.
Characterization
State of the art methods are used to characterize
nanoparticles:
- Particle size distribution
Dynamic Light Scattering is used to measure particles ranging
from a few nanometers to about 3 µm, while Laser Diffraction
is used to detect microparticles or possible aggregates
of drug nanoparticles.
- Particle charge / zeta potential
Our highly experienced staff uses zeta potential measurements
to optimize formulation parameters and to make predictions
regarding the storage stability of the colloidal dispersion.
- Crystalline status
Differential Scanning Calorimetry and other analytical methods
are used to assess any possible changes brought about in
the physical form of the drug during processing.
- Saturation solubility and dissolution rate
Pharmacopoeial methods are used to determine dissolution
rate.
Stability and Release Testing
Cirrus provides full method development
and validation for regulatory submission. Full release testing,
as well as short- and long- term stability testing are available:
- Particle size analysis
- Dissolution
- Chromatography
- Visual evaluation
- Dose content uniformity
- Drug-related impurities
Submission-ready documents will be
generated. If needed, Cirrus will assist the sponsor with
issues regarding FDA regulation.
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