PGSS process

In a relatively new process for production and fractionation of fine particles by the use of compressible media - the PGSS process (Particles from Gas-Saturated Solutions) - the compressible medium is solubilized in the substance which has to be micronized [58-61]. Then the gas-containing solution is rapidly expanded in an expansion unit (e.g., a nozzle) and the gas is evaporated. Owing to the Joule-Thomson effect and/or the evaporation and the volume-expansion of the gas, the solution cools down below the solidification temperature of the solute, and fine particles are formed. The solute is separated and fractionated from the gas stream by a cyclone and electro-filter. The PGSS process was tested in the pilot- and technical size on various classes of substances (polymers, resins, waxes, surface-active components, and pharmaceuticals). The powders produced show narrow particle-size distributions, and have improved properties compared to the conventional produced powders. 

The Joule-Thomson coefficient is the slope of the isenthalpic lines in the P-T projection. In the region where iJt<0, expansion through the valve (a decrease in pressure) results in an increase in temperature, whereas in the region where pJt >0, expansion results in a reduction in temperature. The latter area is recommendable for applying the PGSS process. 

One goal of RESS/CSS, the anti-solvent processes such GAS, and the PGSS process, is to obtain submicron- or micron-sized particles. Technological features of the various high-pressure micronization processes are summarised and compared in Table 9.8-4 [58]. 

Restrictions arising from the difficult product- and gas-recovery in the RESS and GASR, GASP, SAS/PCA/SEDS processes are avoided by the PGSS process. 

The PGSS process has several advantages which favour its use for large scale applications. This process has promise for the processing of low-melting, highly viscous, waxy, and sticky compounds, even if the obtained particles are not of submicron size. The process already runs in plants with a capacity of some hundred kilograms per hour. 

Technological features of RESS, GASR and PGSS process... 

Up to the present time the application of the PGSS process has been investigated for following products ... 

Based on phase-equilibrium data in the Master diagram (Figure 9.8-12) (where S-l and 1-V equilibrium data are presented) the experiments for cocoa butter micronization using the PGSS process were carried out. The pre-expansion pressure was in the range of 60 to 200 bar and at temperatures from 20 to 80°C. The micronization with the nozzle D = 0.25 mm resulted in fine solid particles with median particle sizes of about 62 pm. In Figure 9.8-13 the morphology of a cocoa-butter particle is presented. 

From DSC measurements it was deduced that the crystallinity of a freshly micronized sample is about 80% and that it crystallizes in the stable polymorphic form P2. Under the operating conditions mentioned, the PGSS process caused no degradation of cocoa butter and the product was a powder with a narrow and very controllable size-distribution. 

The practically water-insoluble compounds nifedipine and felodipine, which are dihydropyridine calcium-channel-blockers were processed by the PGSS process with the aim of increasing their dissolution rate and hence bioavailability [71,72]. 

Using the PGSS process, nifedipine was micronized at various pressures in the range from 100 to 200 bar and at temperatures 165, 175 and 185°C. The mean particle-size of the starting... 

The mean particle size of the starting felodipine was 60 pm, and reduced after micronization with the PGSS process to 42 pm. Specific surface areas measured using the BET method increased from 0.33 m2/g for the starting felodipine to 1.33 m2/g for micronized felodipine. 

With the PGSS process, micronized drugs and drug/PEG 4000 samples were prepared in a new way, which has some advantages over conventional methods for the micronization of pure drugs and for drug/carrier solid dispersion preparation, namely fusion methods and solvent processes. 

Figure 9.8.17. Shape of the particles of PEG obtained by the PGSS process.

The advantages of the PGSS process over conventional methods of particle-size reduction are numerous. 

A new developed process PGSS (Particles from Gas Saturated Solutions) was applied for generation of powder from polyethyleneglycols. Principle of PGSS process is described and phase equilibrium data for the binary systems PEG-CO2 for the vapour-liquid and the solid-liquid range are presented in a master diagram . The influence of the process parameters on particle size, particle size distribution, shape, bulk density and crystallinity is discussed. 

For the design of a process for formation of solid particles using supercritical fluids, data on solid - liquid and vapour - liquid phase equilibrium are essential. PGSS process is only possible for systems where enough gas is solubilized in the liquid. 

Composite particles for controlled release of pharmaceutical compounds have been generated by the PGSS process. An example is the formation of 2-3 pm theophylline/hydrogenated palm oil (HPO) particles. The process produced fine and dry powders operating at 60°C and at pressures between 120 and 180 bar. The morphology of the particulates varied with the... 

Rodrigues, M. Peirigo, N. Matos, H. de Azevedo, E.G. Lobato, M.R. Almeida, A.J. Microcomposites of theophylline/hydrogenated palm oil from a PGSS process for controlled drug delivery systems. J. Supercrit. Fluids 2004,29 (1-2), 175-184. 

Figure 7 Schematic flow diagram of the PGSS process for 112, see text.

The PGSS process seems to be very promising, since in addition to the characteristics just listed, other advantages can be taken into account. 

The concept is simple, since the solid and carrier to be micronized do not have to be soluble in the SCF this favors the application of PGSS to a wide range of products. Polymers and generally highly viscous compounds, including waxes, resins, and sticky materials can, be preferentially treated by the PGSS process. 

Figure 2.3-4 Diagram of a PGSS process V = high pressure saturation vessel ...

Different precipitation processes based on supercritical carbon dioxide have been proposed in which CO2 performs different functions as solvent, in the rapid expansion of supercritical solutions (RESS) process, as antisolvent, in the supercritical antisolvent (SAS) process, or as solute, in the particles from gas saturated solutions (PGSS) process. 

---