Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
2000-03-03
2001-09-25
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S451000, C034S329000, C034S337000, C034S341000
Reexamination Certificate
active
06294194
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for improving mass transfer rates into dense fluids and, in particular, supercritical fluids. More particularly, the present invention is directed to a method for removing soluble compositions from materials. The present invention finds application in the removal of manufacture residues such as capsule mold lubricants, in the extraction of desirable material, residual solvents, and contaminants from chemical and pharmaceutical containers and preparations, and in promoting the transfer of reaction products and by-products from catalyst pores to a bulk phase thereby maintaining the activity of the catalyst and improving reaction rates.
2. Background of the Related Art
Extraction procedures are used to transfer solutes from a solid or liquid phase to a gaseous, liquid or supercritical phase. Extensive use is made of solvent extraction in industry. However, it is well known in the art that solvent extraction suffers from a number of drawbacks including environmental and health concerns associated with many solvents, residual contamination of the treated material with the solvent itself, as well as intensive/high costs often associated with conventional extraction-distillation schemes.
Extraction procedures using supercritical fluids (SCFs) rather than organic solvents have been growing in popularity. A fluid whose temperature and pressure are simultaneously higher than its critical temperature and pressure is supercritical. The surprising solubility of solids in SCFs was first noted in the late 1800's (Hannay and Hogarth, Proc. Roy. Soc., London A29, 324 (1879)). Actual solubility of non-volatile solutes in SCFs may be as much as 10
6
times higher than would be calculated assuming ideal gas behavior at the same temperature and pressure.
The most ubiquitous SCF, carbon dioxide (CO
2
, T
c
=304.1 K, P
c
=73.8 bar), is a gas at ambient conditions. In a supercritical state, it is essentially a compressed, high density fluid at mild temperature. It is relatively innocuous, inexpensive and non-reactive under most operating conditions. Other SCFs may have higher T
c
and P
c
and may not be innocuous. Contrary to liquids, the density, solvent power or selectivity of a SCF can be easily altered with relatively small changes in pressure or by addition of small amounts of an organic solvent. The change in CO
2
density (with pressure at 35° C. determined using an equation of state developed specifically for CO
2
) does not increase linearly with increasing pressure. Small changes in pressure can produce large changes in density when operating close to the critical point, for instance at 83 bar where the compressibility of CO
2
is high. Relatively large changes in pressure may result in in relatively small changes in density when operating at higher pressures, for instance at 700 bar where CO
2
compressibility is low.
Because of its gaseous nature, a SCF is also characterized by a higher diffusivity and lower interfacial tension than liquids, and has the ability to freely penetrate a matrix such as pores in a catalyst with no phase change. A SCF such as CO
2
can also be vented out of an extractor, leaving no residue and no need for drying.
Numerous gases other than CO
2
may be converted to SCFs at temperatures and pressures commonly employed in industry, including, without limitation, hydrocarbons (e.g. methane, ethane, propane, butane, pentane, hexane, ethylene and propylene), halogenated hydrocarbons, and inorganic compounds (e.g., ammonia, carbon dioxide, sulfur hexafluoride, hydrogen chloride, hydrogen sulfide, nitrous oxide and sulfur dioxide). SCFs have been used to extract numerous compounds including aliphatic and aromatic hydrocarbons, organic esters of inorganic acids, organosilicons and organometallics.
SCFs have found a particular niche in cleaning items. U.S. Pat. No. 5,267,455, incorporated by reference herein, discusses a number of references which disclose the use of SCFs to remove materials as diverse as oil and carbon tetrachloride residues from metals to soils from garments. SCFs have also been used as extracting agents to deasphalt lubricating oils, to obtain edible oils, and decaffeinate coffee (Zosel, U.S. Pat. No. 3,806,619).
SCFs have been reported to be useful in other extraction applications including re-dissolution of adsorbed material (U.S. Pat. No. 4,061,566), the formation of porous polymers, removal of residual solvents from articles formed by compression such as tablets (U.S. Pat. No. 5,287,632), monomer purification and fractionation of various polymers. A possible drawback of SCFs such as CO
2
is that they generally have limited solvent power for many polar and high molecular weight compounds. Therefore, they are often used for material purification or selective extraction.
SCFs are also used for crystallization (See, e.g., U.S. Pat. Nos. 5,360,478 and 5,389,263) as well as micronization of solutes in organic solutions (See, e.g., U.S. Pat. No. 5,833,891). Solutes may also be micronized by rapidly expanding a SCF solution down to a pressure where the solute is no longer soluble.
Use of SCFs as reaction media includes applications for chemical deposition of a reaction product on substrates (See, e.g., U.S. Pat. No. 4,970,093), oxidation of organics in water (Modell, U.S. Pat. No. 4,338,199), and maintenance of catalyst activity (U.S. Pat. Nos. 4,721,826 and 5,725,756). For example, Tiltsher et al. (Angew. Chem. Int. Ed. Engl. 20:892, 1981) report that the activity of a porous catalyst can be restored by elevating pressure or temperature to a level where the deposited coking compounds are re-dissolved in a supercritical reaction mixture. However, on a whole, catalyst reactivation and deactivation using SCFs has yet to become adopted widely in the industry possibly due to either low catalyst activity when compared to the alternate industrial processes in place, or because catalyst activity is not maintained at a reasonably high level for long enough time. Applicants have hypothesized that diffusion limitations of reactants, products, and catalyst deactivating material are still present, thereby limiting the usefulness of these techniques.
A substantial discussion of the many uses to which SCFs have been employed is set forth in the text
Supercritical Fluid Extraction
by Mark McHugh and Val Krukonis (Butterworth-Heinmann 1994).
While SCFs proffer many advantages over organic solvents, several investigators have noted drawbacks with conventional supercritical fluid extraction (SFE) procedures. A problem associated with SCFs is the low mass transfer rate of a solute in a confined space to a bulk supercritical phase. The rate of solute extraction depends on the solute's dissolution rate, solubility, and rate of mass transfer into the bulk solvent phase. Despite higher diffusivity than liquids, SCFs still exhibit limited ability to rapidly transfer extracted material from confined spaces to a bulk supercritical phase. Lack of thorough mixing between the fluid in the bulk phase and the fluid in the confined space limits mass transfer to essentially the diffusion rate of the solute(s). Normally, dissolution and mass transfer rates can be enhanced by thorough mixing between a bulk phase and a solute phase as by means of an impeller; however, the degree of enhancement in mass transfer rates is limited when the solute resides in confined spaces such as micropores, interstices, nearly closed containers or closed containers where little mixing will take place. In these cases, interphase mass transfer between the fluid in the confined spaces and the fluid in the bulk phase is often a rate limiting step.
A variety of applications in the pharmaceutical, chemical and other industries suffer from problems associated with slow mixing between a fluid or fluid mixture in a confined solid space, and a fluid or fluid mixture in a bulk phase. These problems can be so severe that they can reduce the efficiency of the process, sensibly increase processing cos
Horhota Stephen T.
Saim Said
Boehringer Ingelheim Pharmaceuticals Inc.
Devlin Mary-Ellen M.
Page Thurman K.
Raymond Robert P.
Seidleck Brian K.
LandOfFree
Method for extraction and reaction using supercritical fluids does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for extraction and reaction using supercritical fluids, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for extraction and reaction using supercritical fluids will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2540116