Rapid Expansions of Supercritical Solutions RESS

A number of techniques are based on supercritical fluid technology. Three are of particular pharmaceutical interest, namely the supercritical antisolvent (SAS) system, the rapid expansion of supercritical solution (RESS) method, and the gas antisolvent (GAS) technique [126]. 

The Chinese scientists [123] have reported the preparation of nanoscale RDX (-50 nm) and nanoscale HMX (=70 nm) by an impinging method [124]. Researchers from China have also reported preparation and characterization of n-NTO and their data indicate that it decomposes at a lower temperature and at the same time, it is less sensitive to impact compared with m-NTO. This property of n-NTO is likely to be of tremendous significance for insensitive munitions [125]. The preparation of n-RDX particles with a mean size (=110-120 rim) but narrow distribution has also been reported by a novel method known as rapid expansion of supercritical solution (RESS) [126]. 

Turk, M., B. Helfgen, P. Hils, R. Lietzow, and K. Schaber. 2002. Micronization of pharmaceutical substances by rapid expansion of supercritical solutions (RESS) Experiments and miRtetio ... 

A novel fluidized-bed coating process using the rapid expansion of supercritical solutions (RESS) is described for the encapsulation of fine particles [2,3]. This process exploits the capability of supercritical fluids to act as a selective solvent. Supercritical fluids are noteworthy in that their... 

The rapid expansion of supercritical solutions (RESS) has been explored recently as a novel route for the production of small and monodispersed particles (1-2.). Particle formation involves nucleation, growth and agglomeration. In RESS, nucleation is induced by a rapid decompression growth and agglomeration occur within the expanding solution. The thermodynamics of the supercritical mixture influences the relative importance of these mechanisms, and thus play a key role in sizes or size distribution of final particles. 

Several new processes for formation of solid particles with defined particle size and particle size distribution using supercritical fluids were developed in the past years. Examples are crystallisation from supercritical fluids, rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallisation (GASR), and PGSS (Particles from Gas Saturated Solutions)-process [1,2]. 

Production of fine, solvent free powders is of great importance in the pharmaceutical industry /5/. Conventional techniques produce particles with broad particle size distributions. Moreover, particles may be irregular or contain solvents. Hence the development of procedures such as Rapid Expansion of Supercritical Solutions (RESS) or the Gas Antisolvent Recrystallisation (GAS) is in progress /5, 6/... 

A pilot plant is presented, which has been built to prepare fine particles (< 4 pm) by the Rapid Expansion of Supercritical Solutions (RESS - process). In this study carbon dioxide loaded with anthracene was used. By varying process parameters, the particle size distribution can be influenced. Changes of the post-expansion pressure have no provable influence on the particle size distribution. 

The rapid expansion of supercritical solutions (RESS) was explored by several authors as a novel route to the formation of microparticles. Ohgaki [1] produces fine stigmasterin particles by the rapid expansion of a supercritical C02 solution. Amorphus fine particle and whisker-like crystals (0,05 - 3 pm) were obtained with different preexpansion pressures. Johnston [2] obtained submicron particles from different polymers. Loth [3] described the mirconisation of phenacetin with supercritical fluids. 

The supercritical fluid mefhod is a relafively new method, which can minimize the use of organic solvents and harsh manufacturing conditions taking advantage of two distinctive properties of supercritical fluids (i.e., high compressibility and liquid-like density). This method can be broadly divided into two parts rapid expansion of supercritical solutions (RESS), which utilizes the supercritical fluid (e.g., carbon dioxide) as a solvent for the polymer, " and supercritical antisolvent crystallization (SAS), using the fluid as an antisolvent that causes polymer precipitation. Recent reviews of the supercritical technology for particle production are available in the literature. ... 

Turk, M. Hils, P. Helfgen, B. Schaber, K. Martin, H.-J. Wahl, M.A. Micronization of pharmaceutical substances by the Rapid Expansion of Supercritical Solutions (RESS) a promising method to improve bioavailability of poorly soluble pharmaceutical agents. J. Supercrit. Fluids 2002, 22 (1), 75-84. 

The first supercritical fluid-based micronization process has been the rapid expansion of supercritical solutions (RESS) it is based on the solubilization of the solid to be micronized in the SCF and its subsequent precipitation by fast depressurization of the solution. However, the use of this technique is largely limited by the low solubility in supercritical carbon dioxide (SC-CO2) of many of the solids of interest. " ... 

Supersaturation of solutions to precipitate ceramic powders is attained by means of supercritical fluids. This technique, termed rapid expansion of supercritical solutions (RESS), is reviewed elsewhere. ... 

The rapid expansion of supercritical solution (RESS) process consists of dissolving the product in a supercritical fluid (usually carbon dioxide) and then rapidly depressurizing the solution through a spray nozzle thus causing extremely rapid nucleation of the product into a highly dispersed material. Various technologies based on supercritical fluids are given in Table 5.5. 

In the first method, the drug is dissolved in the SF and followed by rapid expansion of the SF solution across a heated orifice to cause a reduction in the density of the solution and reducing the salvation power of the SF, which leads to the precipitation of the drug [16]. This process is termed the rapid expansion of supercritical solution (RESS). 

Microsphere formation and encapsulation by the Rapid Expansion of Supercritical Solutions (RESS) technique... 

Rapid expansion of supercritical solutions (RESS) processing is used to prepare microspheres. Microencapsulation takes place when a pressurized supercritical solvent containing the shell material and the active ingredient is released through a small nozzle the abrupt pressure drop causes the desolvation of the shell material and the formation of a coating layer around the active ingredient (74). A prerequisite for this technology is that the compounds effectively dissolve in the SCF, which limits its application. 

Franck SG, Ye C. Small particle formation and dissolution rate enhancement of relatively insoluble drug using rapid expansion of supercritical solution (RESS) process. Proceedings of the 5th International S5miposium on Supercritical Fluids, 8-12, April, Atlanta, 2000. 

Physical mixtures of powders have also been produced by using the rapid expansion of supercritical solution (RESS) process technique (40,41). Twelve different mixtures of drugs and impurities were evaluated in a study... 

As described in Chapter 3, several SCF techniques are available for the preparation of drug delivery systems. These include rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallization (GAS), supercritical antisolvent recrystallization (SAS), supercritical antisolvent with enhanced mass transfer (SAS-EM), solution-enhanced dispersion by supercritical fluids (SEDS), supercritical fluid nucleation (SFN), precipitation with compressed antisolvent (PCA), and aerosolized supercritical extraction of solvents (ASES). While RESS and SFN involve the expansion of a supercritical fluid solution of a drug to form drug particles, GAS, SAS, SAS-EM, SEDS, PCA, and ASES use a supercritical fluid as an antisolvent to precipitate particles of a drug dissolved in an organic solvent (5). General RESS and GAS processes are further elaborated in Sections 1.1.1 and 1.1.2. 

Debenedetti PG, Tom JW, Kwauk X, Yeo SD. Rapid expansion of supercritical solutions (RESS) fundamentals and applications. Fluid Phase Equilibria 1993 82 311-321. 

Chernyak Y, Henon F, Harris RB, Gould RD, Franklin RK, Edwards JR, DeSimone JM, Carbonell RG. Formation of perfluoropolyether coatings by the rapid expansion of supercritical solutions (RESS) process. 1. Experimental results. Ind Eng Chem Res 2001 40 6118-6126. 

---