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Production of nanoparticles using subcritical carbon dioxide

Prof. M. Mukhopadhyay and her student of Department of Chemical Engineering have developed a new drug delivery system with a prolonged bio-activity and enhanced drug dissolution rate. The efficiency of any drug depends upon their size, morphology and size distribution, as their solubility in the body fluid depends upon these factors. Lower the particle size of these solid drugs, higher would be their dissolution rates and their bioavailability in the body fluids.

For new drug delivery systems like dry powder inhalers, needle-free injections and controlled release devices, there is a long-felt requirement for micronized drugs with a narrow particle size distribution (PSD) for enhancement of drug dissolution rate and bio-activity and elimination of repetitive or excessive dosage. Scientists have developed crystallization processes where supercritical carbon dioxide (SC CO2) is used to produce nano/ultra-fine particles.

However, these SC CO2 processes have most of the following disadvantages:
(i) very high pressure requirement
(ii) high pressure CO2 pumps
(iii) fine nozzle devices for spraying which is prone to clogging
(iv) accurate control of pressure, temperature, flow rates and concentration
(v) usage of a large amount of SC CO2 for removal of solvent

To solve the above-mentioned disadvantages, a process has been developed in IIT Bombay for production of nanoparticles of solids soluble in organic solvents by using sub-critical carbon dioxide. In this process CO2 at a low initial pressure in the range of 25-70 bar and a near ambient temperature is used to avoid the usage of any equipment for generation of high pressure and high temperature. Furthermore, in this process the use of depressurization of the solution is avoided and so the use of specially designed nozzles is not required.

This newly invented process involves (i) dissolution of the solid substance in an organic solvent (ii) pressurizing the solution with CO2 to attain a pressure of 25-70 bar and then (iii) bleeding off CO2 over the solution for drastic lowering of the solution temperature within a time span of 0.5 to 5 minutes. This causes extremely high, very rapid and uniform supersaturation in the solution leading to crystallization of the solid to nanoparticles with narrow particle size distribution.

Indian patent application no. 544/MUM/2004 Patent grant no. 213605
Inventors: S Dalvi and M Mukhopadhyay


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