Professional Documents
Culture Documents
Seminar Presentation
Seminar Presentation
Contents
2
Introduction Standard
micronization processes Vs supercritical fluid based techniques Supercritical fluid properties Particle formation processes with supercritical fluids Advantages Limitations Future perspective
Introduction
3
conventional drug delivery systems and controlled drug delivery systems Traditionally distinct solid forms are prepared by precipitation, grinding, evaporation, milling, freeze drying, spray drying, etc.
Introduction
4
represented by the supercritical fluid(SCF) technology Micronisation of API using SCF technology eliminates disadvantages of traditional processes
Crystal
Density
Structure
solid dosage forms with suitable physicochemical properties Control biopharmaceutical properties Maximize the efficiency and minimize the required dosage Optimize the formulation
is important for
stress
& agglomeration
The
are
SCFs
intermediate
are highly
Near
used Low and easily accessible critical temperature (31.2C) and pressure (7.4MPa) Inflammable Non-toxic Inexpensive
solvation power, while the viscosity and diffusivity facilitate the mass transfer Homogeneous and opalescent system without phase separation The solvent like properties are beneficial for drug solubilisation, polymer plasticization and extraction of organic solvents or impurities
with relatively small quantities of organic solvent(s) Molecular control of process Single step, scalable process for solvent-free final product
Ability
Suitable
system
GMP
compliant process
1. RESS
2. GAS/ SAS 3. ASES 4. SEDS 5. PGSS
Mechanism
Product
15
RESS Equipment
Process Variables
Supersaturation
ratio
Temperature Pressure
solubility in SCF of orifice (expansion device) conditions in precipitator phenomena during expansion
Dimensions
Mechanism
Step 1
Antisolvent Solution of Active Substance
Step 2
Mixing, expansion and supersaturation of solution mixture
Step 3
Solute precipitates in microparticles
I. Pasquali et al., Adv. Drug Deliv. Rev. 60:399-410 (2008).
18
GAS/SAS Equipment
Process variables
Rate of
Temperature
addition of antisolvent
solubility in organic solvent insolubility in SF of expansion of organic solvent in SF solvent/SF antisolvent ratio
Rate
Pressure/temperature Phase
nucleation
Mechanism
Step 1
Spraying of active substance & solvent mixture
Step 2
Step 3
22
ASES Equipment
Process Variables
Temperature
Liquid solution
pressure
Operating
vessel pressure
J. Jung, M. Perrut. J. Supercrit. Fluids. 20:179-219 (2001).
Degree
Dimensions Temperature
of operating vessel
Mechanism
Particle precipitation
25
SEDS Equipment
Process Variables
Type of nozzle
Combination of
processing media
Temperature
J. Jung, M. Perrut. J. Supercrit. Fluids. 20:179-219 (2001).
Advantages
It
Binary
Suitable
Highly
Manufacturing
Mechanism
28
PGSS Equipment
Process Variable
Pressure
Temperature
Advantages
30
operating temperatures step process and recycle of fluid technology free products
single
Advantages
31
SEM images
of nabumetone
(b) After RESS process
Advantages
32
Mean particle size= 32.6 m (original) Mean particle size= 3.3 m (processed)
Limitations
33
aggregation
blockage
lost
N2O and light hydrocarbons are hazardous and less environment
friendly
P. York. Pharm. Sci. Technol. Today. 2:430-440 (1999).
Conclusion
34
be better
Feasibility to produce particle under cGMP conditions Up to certain extend limitations of conventional processes
Future Perspective
35
The
largely unexplored.
The universality of SAS will ensure future developments Multidisciplinary
approach
should
be
focused
on
concepts
of
clean
or
green
chemistry
and
sustainable technology
Thank You
36