Institute for Technical Thermodynamics and Refrigeration Research group of Prof. Dr.-Ing. Michael Türk
Controlled Particle Deposition drugs with improved dissolution performance Sarah Reiser (
[email protected]), Michael Türk
Motivation
Wouldn‘t it be nice to take a fast-acting drug?!
12 Do you have a headache? 3
9 6
Background Improvement of solubility
Particle size reduction with supercritical CO2
Resorption depending on solubility and permeation Solubility BCS:
• Particle size reduction • Decrease in hydrophobicity and/or crystallinity • Use of cosolvents, solubilizers, surfactants • pH-value, temperature • D
Processes: • Rapid Expansion of Supercritical Solutions • Controlled Particle Deposition
Permeation
Challenge
IV II
III I
(Biopharmaceutical Classification System)a
Supercritical CO2 liquid
scf
Pressure
solid CP
gas TP
Advantages: • Narrow particle size distribution • No thermal or chemical degradation of the product • Solvent-free final product
Temperature
• Tc = 304 K pc = 7.4 MPa • Gas-like viscosity • Liquid-like density
Controlled Particle Deposition process Process
Pharmaceutical drugs
Carrier materials
Mechanism CH3 OH
• R/S-Ibuprofen
CH3 O H3C
• R/S-Flurbiprofen Drug
Carrier
O
• R/S-Ketoprofen
CH3 OH O
• • • •
Physisorption Chemisorption Inclusion complexes D
SBA-15
ß-Cyclodextrin
~1030 m2/g
~920 m2/g
