AU760327B2 - Method for the purification and recovery of waste gelatin - Google Patents

Description

-1- METHOD FOR THE PURIFICATION AND RECOVERY OF WASTE GELATIN Field of the Invention This invention is generally directed to a process for recovery, purifying and recycling gelatin waste made from gelatin and derivatives thereof and in particular, to a process for recovery, purifying and recycling gelatin waste, its derivatives, and components contained within gelatin waste resulting from industrial encapsulation processes.

Background of the Invention Any discussion of the prior art throughout the specification should in no way be io: 10 considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.

Gelatin and gelatin derivatives are used to encapsulate the products of several industries. Examples are described in U.S. Pat. No. 5, 074, 102, issued to Simpson et al, and include the encapsulation of medicinal compounds such as drugs and vitamins; 15 employment of gelatin encapsulation in food packaging, such as for powdered instant coffee or spices; in candy manufacturing; in fertilization of ornamental plants and/or indoor plants; in packaging of sensitive seeds in combination with protective agents and/or fertilizers; and in the packing of single dyestuffs or mixtures of various drugs.

In each of the above-recited manufacturing and production processes, a certain 20 amount of the encapsulating material and the encapsulated material vitamins) is WO 00/29097 PCT/US99/27095 lost as waste. Frequently, the amount lost as waste of the encapsulating material approaches 50% or more of the total starting material, depending on the arrangement of production employed. When considering that the cost of the encapsulating material in the United States averages approximately $3.10 per pound ($6.82 per kilo) as of September, 1997, it is clear that the economic consequences of such waste can be significant. As a result, manufacturers have attempted to off-set poor production efficiency by recycling the waste material for reuse. Such attempts, however, have not been met with a great deal of success.

Prior art methods of gelatin recovery and purification suffer from a variety of shortcomings to be discussed in further detail below. Before these shortcomings can be fully appreciated, however, the composition of the encapsulation waste material itself should be further understood. In general, waste material of encapsulation processes is comprised of a variable number of components added to a gelatin base. Among them are solvents (usually water); softening agents and oil coatings (when desired); and, contaminants in the form of residual active ingredients, i.e. the substance being encapsulated. In addition, colorings and preservatives may also be added. Thus, it can be observed that successful recycling involves not only the recovery of gelatin from surrounding oils, but also the removal of the remaining components of the waste in order to achieve a relatively pure, reusable product.

WO 00/29097 PCT/US99/27095 Extraction has been the principle method for accomplishing removal of oils, actives and the like in the pharmaceutical industry. While several solvents have been used in the prior art in an effort to accomplish separation, each suffer from a variety of shortcomings not the least of which is the necessity of ultimately removing yet another component, i.e. the solvent itself, from the recycled materials. To date, the most popular and widely used solvents used to separate gelatin from oils and actives are chlorinated solvents such as, for example, 1,1,1 ,-trichloroethane with naphtha. The use of chlorinated solvents, however, is accompanied by high costs, disposal problems, and most importantly, environmental concerns. Attempts have been made to use other solvents including isopropyl alcohol, methyl isobutyl ketone, toluene, hexane, heptane, acetone, and acetone/water mixtures, but the resulting yields are insufficient and/or the separation is poor. Furthermore, some of these chemicals are relatively expensive and present similar environmental, disposal, and safety concerns as the chlorinated solvents. None of them have been found to separate oils and actives with a high degree of efficiency.

U.S. Patent No. 5,288,408, issued to Schmidt et al, discloses a method of recycling gelatin-based encapsulation waste material, and more specifically, to a process for the recovery and purification of gelatin and softening agents therefrom. In the preferred embodiment, deionized water is added to the waste material thereby forming an aqueous solution of gelatin and glycerin dispersed within the remaining oil and residual active-ingredient components of the waste material. Extraction methods WO 00/29097 PCT/US99/27095 are employed under specific conditions to effect separation of the lower aqueous phase from the upper oil phase. The lower phase is hot filtered to remove any remaining traces of oil or other contaminants and the filtrate is then charged to a concentration vessel adapted for vacuum distillation. The water solvent is thus removed under specific thermal and atmospheric conditions until the desired concentration of gelatin and glycerin is achieved. A pure, concentrated aqueous gelatin-glycerin solution results which may be stored or further prepared for immediate reuse. Although this process lends itself to the removal of dyes and active ingredients with additional chemical reactions and processing, such dyes, active ingredients, and glycerin are not removed in situ.

Clear gelatin contains no dye, colorants or the like. It is used to make clear gelatin capsules in the pharmaceutical, neutraceutical, and nutrient industries and other industries as well. Because dyes are not present, there is a need to provide a cost efficient and effective manner for recycling the gelatin and glycerin for reuse. Gelatin may have suspended particles such as titanium dioxide which impart a color to the gelatin. Such particles can be more easily removed from the waste gelatin than dyes and colorants which are water soluble.

It would, therefore, be desirable to provide a method for recycling gelatin-based encapsulation waste material that recycles gelatin and glycerin in situ without the need for any-additional processing. It would be a further advance in the art of recycling waste gelatin of an in situ process could be developed especially effective in recycling gelatin and gelatin containing suspended particles without thermal degradation in a cost efficient and effective manner. It would be a still further advance in the art to provide a cost efficient and effective method of recycling gelatin whether clear or colored and whether or not the gelatin contains suspended particles a colorant).

It would be a still further advance in the art to provide a method of recovering valuable components from a waste gelatin recovery process.

Summary of the Invention The present invention is generally directed to the recovery of waste gelatin alone or in combination with other components of a waste gelatin product through the separation and treatment of a waste gelatin stream into an aqueous and non-aqueous substream.

In a first aspect, the present invention provides a method of treating a waste material containing gelatin comprising: a) combining the waste material and a solvent for the gelatin under sufficient conditions to form a first liquid containing gelatin, said waste material o• containing at least one first component which can not effectively be separated from the first liquid into a non-solvent based layer; b) separating the liquid into a solvent based layer containing the gelatin and said at least one component and a non-solvent based layer; and c) treating the solvent based layer with a process which removes the first component from the solvent based layer to form a second liquid containing gelatin S having a higher purity than the first liquid being at least substantially devoid of the first I Z- -6- In a second aspect, the present invention provides an apparatus for treating a waste material containing gelatin comprising: a) means for combining the waste material and a solvent for the gelatin under conditions sufficient to form a first liquid containing gelatin, said waste material containing at least one first component which can not effectively be separated from the first liquid into a non-solvent based layer; b) separation means for separating the first liquid into a solvent based layer containing the gelatin and said at least one first component and a non-solvent based layer; and c) treatment means for treating the solvent based layer to remove the first component from the solvent based layer to form a second liquid containing gelatin having a higher purity that the first liquid and being at least substantially devoid of the first component.

In a third aspect, the present invention provides a waste material containing gelatin treated by a method according to the first aspect.

If desired, the second liquid may be concentrated by removing at least some of the solvent, solvent soluble active ingredients, softening agents, dyes and other solvent soluble impurities to provide at least a substantially purified second liquid.

Unless the context clearly requires otherwise, throughout the description and the claims, the words 'comprise', 'comprising', and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to".

6a- Brief Description of the Drawings The following drawings in which like reference characters indicate parts are illustrative of embodiments of the invention and are not intended to limit the invention as encompassed by the claims forming part of the Application.

Figure 1 is schematic view of an embodiment of the method of gelatin recovery and purification in accordance with the present invention; and Figure 2 is a schematic view of a further embodiment of the invention similar to Figure 1 in which a separate, external degassing operation is provided to remove dissolved gases air) from the recovered gelatin.

WO 00/29097 PCT/US99/27095 Detailed Description Of The Preferred Embodiments Gelatin is a protein derivative of collagen obtained, in general, by the boiling of skin, white connective tissues, and bones of animals, and by the partial hydrolysis of collagen, in particular. As a colloid it has unique physical properties. Of particular significance to the present invention is its tendency to stay ip solution and its ability to form dispersions in oils. Gelatin remains a solid at standard atmospheric pressure and temperature absent the presence of a sufficient quantity of solvent.

Softening agents are sometimes added to plasticize the gelatin when soft, gelatin shells are desired. Agents such as glycerin, sorbitol, or other similar polyols are commonly employed as softening agents. Glycerin is a preferred softening agent.

The soft elastic capsule-forming material may be used to enclose active components in the form of powders, liquids, or combinations thereof. Oils, such as vitamin A, vitamin E, and beta-carotene, for example, are frequently encapsulated by such soft gel materials in the pharmaceutical, cosmetic, and nutritional industries.

Additionally, other oils like mineral oil or medium chain triglycerides (MCT's) may be used to coat the outer surface of the gel-capsule during processing. Thus, it can be seen that the waste product of the encapsulation process may have, in addition to gelatin and a softening agent such as glycerin, many components oily components) which must be removed before the gelatin waste is available for reuse as -7- WO 00/29097 PCT/US99/27095 a relatively pure product. In some instances, coloring agents and preservatives may also be incorporated into the gelatin mass. Commonly used preservatives include methylparaben, propylparaben, and sorbic acid.

Present methods of encapsulating active components employ a ribbon or sheet of gelatin which is then die punched to form capsules. As much as 50% or more of the gelatin starting material gelatin ribbon) is either discarded as a waste by-product or recycled. The latter option requires the removal of all of the above-mentioned components. The present invention provides a novel and efficient method of purifying and recycling the waste material without experiencing the shortcomings of the prior art.

It will be understood that other proteins with i hysical and chemical properties similar to gelatin exist and may also be recycled by the present process. Similarly, glycerin is only one example of a softening agent which may be recovered; thus, neither gelatin nor glycerin are intended to be limiting.

Reference is now made to Figure 1 wherein an embodiment of the present invention for the purification and recovery of gelatin and/or glycerin is illustrated. A suitable solvent such as deionized water is added through a conduit 2 in an amount sufficient to dissolve the waste gelatin material, typically in an amount of up to about five volumes, based on the quantity of waste gelatin, preferably from about to 5.0 volumes is added to a dissolution/separation vessel 4 which may be provided with a heating jacket known in the art. The solvent is preheated to a temperature of WO 00/29097 PCT/US99/27095 from about 30 to 70°C to make the waste gelatin in a convenient flowable condition. The waste gelatin material is then charged either batchwise or continuously to the dissolution/separation vessel 4 via a conduit 5 which may be made of stainless steel or glass-lined construction and sized according to a desired batch size. The dissolution/separation vessel 4 may also be provided with a conventional agitation device such as a stirrer (not shown). The waste material to be recovered is diluted with the solvent deionized water) typically at atmospheric pressure under heating at a temperature from about 30 to 70'C to a preferred concentration of from about 8% to gelatin by weight. Agitation is simultaneously performed to effect dissolution of the gelatin and the softening agent glycerin).

A solution of gelatin and glycerin solvent based layer aqueous layer)] is thus formed within the remaining oily component and residual active-ingredient components non-solvent based layer non-aqueous layer)]. As used herein the term "solvent based layer" shall mean a layer or phase in which the components contained therein are dissolved in the solvent. The term "non-solvent based layer" shall mean a layer or phase in which the components therein do not dissolve in the solvent and therefore may be separated from the solvent based layer. Since water is the preferred solvent, reference will be made hereinafter to the aqueous layer and nonaqueous layer.

WO 00/29097 PCT/US99/27095 The above recited concentration level of gelatin (from about 8% to 45%) is a preferred concentration for achieving rapid and thorough separation of the upper nonsolvent based layer non-aqueous layer) from a lower solvent based layer (e.g.

aqueous layer). The upper non-aqueous layer is either discarded or sent via a conduit 6 to a recycling system 8 which is known in the art. If recycled, the non-aqueous layer may be separated into oily components including, but not limited to, vitamins (for vitamin containing products vitamin mineral oil, garlic oil, fish oil, beta carotene, and vitamin E, which emerge through conduit Once the gelatin is completely dissolved within the vessel 4, agitation is terminated and the mass is allowed to either 1) stand to effect separation of the solvent based layer aqueous layer) from the non-aqueous layer then further processed to remove residual oils and/or particulates or, 2) alternatively, the entire mass may be sent directly to an appropriate apparatus for separation of the aqueous and non-aqueous layers.

If the mass is allowed to stand to effect separation of the oils, it has been observed that for a batch size of about 150 Kg, for example, approximately I to 3 hours were required for separation. Separation of the lower aqueous layer from the upper non-aqueous layer within the vessel 4 can be facilitated by a sight glass incorporated into the recycling system 8. Accordingly, differences between the two layers are visually determined to effect accurate separation. Alternatively, an oil skimmer may be WO 00/29097 PCT/US99/27095 employed to remove the non-aqueous layer, as previously indicated, which is discarded or further processed in the recycle system, while the lower aqueous layer is further processed as discussed below.

The separation and recovery of the individual oily components within the nonaqueous layer of the recycling system can be accomplished by a variety of processes including, but not limited to, fractional distillation, short path distillation, and reverse osmosis.

In general, distillation is a process in which a liquid is vaporized, recondensed, and collected in a receiver. The liquid which has vaporized is collected in a receiver.

The resultant liquid condensed vapor) is referred to as the condensate or distillate.

Distillation is a process for purifying liquids by separating the liquid into its components. It is based on the difference in the volatility of the liquids. Volatility is a general term used to describe the relative ease with which molecules (liquid or solid) may escape from the surface to form a vapor. The vapor pressure of a liquid is related to the ease with which the liquid volatilizes a relatively volatile substance exerts a relatively high vapor pressure at room temperature). The more volatile a substance, the higher its vapor pressure and the lower its boiling point.

-11- WO 00/29097 PCT/US99/27095 Fractional distillation is the separation and purification, by distillation, of two or more liquids into various fractions. It is a systematic redistillation of progressively purer distillates or fractions. A fractionating column is used to essentially perform a large number of successive distillations without the necessity of actually collecting and redistilling the various fractions. A fractionating column may be packed with glass beads, glass helices, metal screens or ceramic saddles to effect fractionation.

A series of distillations involving partial vaporization and condensation concentrates the more volatile component in the first fraction of distillate and the less volatile component in the last fraction or in the residual liquid. The vapor leaves the surface of the liquid and passes up the packing of the column. The vapor condenses on the cooler surfaces and redistills, typically many times before entering the condenser. By means of long and efficient distillation columns, two liquids may be completely separated.

Short path distillation is especially suitable for substances that cannot be distilled by any of the ordinary distillation methods because the substance is viscous, and any condensed vapors tend to plug the distilling column or condenser; and/or the vapors of the substance are extremely susceptible to condensation.

Short path distillation differs from other distillations because a condensed vapor flows to the distillate receiver or collector; very low pressure (high vacuum) -12- WO 00/29097 PCT/US99/27095 in the system favors vaporized molecules reaching the condensing surface without collision with other molecules to condense prematurely; there is a very short distance between the surface of the evaporatingliquid and the condenser surface; and the substance has a residence time in the presence of heat which is very short so that thermal degradation is prevented.

A short path distillation apparatus typically includes a rotating still. Materials are fed into the rotating still and distributed evenly and thinly over a heated evaporating surface. The substance distills in a short time and the vapors condense and run into a collector. The degree of vacuum is controlled to collect the distillate effectively at the condenser. The pressure can be as low as 1 pm Hg.

Short path distillation as described herein is also known as molecular, wiped film, thin film, falling film, and rising film distillation. Short path distillation systems are commercially available from companies such as Pope Scientific in Saukville, Wl and Artisan Industries in Waltham, MA.

Reverse osmosis is a process whereby dissolved solids or a miscible liquid are removed from water by applying a pressure differential across a semi-permeable membrane. The semipermeable membrane allows water to flow therethrough, but does not allow other components from passing through the membrane. Reverse osmosis -13- WO 00/29097 PCT/US99/27095 equipment is commercially available from companies such as Pall Filtron in Northborough, MA and Millipore Corporation in Bedford, MA.

As described above, the dissolved gelatin is separated into a solvent based layer aqueous layer) and a non-solvent based layer non-aqueous layer). The nonaqueous layer is then treated by any of the above described methods to recover the oils contained in the non-aqueous stream.

If the separated aqueous layer contains particulates and/or oily type materials, the aqueous layer may then be treated, to remove residual oils and/or particulates preferably by means of hot filtration processes as more fully described below.

The aqueous layer is sent through a heated transfer conduit 14, to a hot filtration assembly 18. The hot filtration assembly 18 is particularly desirable if the aqueous layer contains particulate matter or residual oil matter.

The method of hot filtration employed for the removal of oils and/or particulates may include, but is not limited to, techniques such as liquid:liquid centrifugation, submicro/micro-filtration, liquid:liquid coalescers, absorbents and filter aids such as, but not limited to, diamataceous earth, activated carbon, clay or activated clay, colloidal silica, porous acrylic resins and the use of oil soluble salts to break any emulsion that may exist.

-14- WO 00129097 PCT/US99/27095 Liquid:liquid centrifugation is based on the principal that the rate of separation of two immiscible liquids is increased significantly by the application of centrifugal force which can be thousands of times that of gravity. The force exerted on the liquids is directly proportional to the speed of rotation, the radius of rotation, and the mass of the liquids.

The force exerted on rotating immiscible liquids, i.e, aqueous and non-aqueous liquids, is described in terms of relative centrifugal force or number of g's which is expressed as multiples of the force of gravity. Centrifuges are rated by their relative centrifugal force which can typically range from 10 to hundreds of thousands. Relative centrifugal force can be controlled by varying the speed or the centrifuge head or rotor.

As a method of hot filtration in the subject invention, the aqueous layer to be hot filtered is maintained at a temperature sufficient to allow flow into the centrifuge; higher temperatures and/or higher dilutions may also enhance an efficient separation by reducing the viscosity of the liquids to be separated. A temperature of from about to 70°C and a dilution volume of up to 5 volumes, preferably from about 0.5 to volumes of a suitable solvent, such as water, is preferred.

The efficiency of separation may be enhanced by employing a relatively higher centrifugal force in the range of from about 5,000 to 25,000. The resulting, clarified aqueous layer containing gelatin and glycerin is collected for reuse and the residual oils WO 00/29097 PCT/US99/27095 and/or particulates are either discarded or collected for potential recovery as discussed hereinafter.

Liquid:liquid:solid centrifugation can also be utilized to achieve separation of the gelatin and softening agent glycerin) from the particulates and/or residual oils.

This procedure is preferred when the waste gelatin stream contains particulates which are at least a part of the coloring system titanium dioxide).

Commercial liquid:liquid and/or liquid:liquid:solid centrifugation equipment is available from companies such as Westfalia Separator U.S. in Northvale, NJ and Alfa Laval in Warminster, PA.

Micro or sub-micro filtration refers to a method of removing small particles from a liquid. Particulates as used herein include, but are not limited to, solid particulates which do not have sufficient mass to settle out of solution and/or emulsions and microemulsions which do not readily separate from a liquid. Micro or sub-micro filtration can be achieved through the use of micron or sub-micron pore sized filters including, but not limited to cartridge type filters, also known as "depth" or "dead end" filters and tangential flow type filters. Tangential flow type filters are the preferred filters for this purpose. The pore size of the preferred filters is typically in the range of from about 0.1 and 2.0 microns.

-16- WO 00/29097 PCT/US99/27095 Temperature and dilution are important considerations in improving the efficiency of the filtration process by varying the viscosity of the liquid. A temperature of from about 300C to 700C and a dilution volume of up to 5 volumes preferably from about to 5 volumes of a suitable solvent, such as water, is preferred.

Micro or sub-micro filtration equipment is commercially available from suppliers such as Millipore Corporation in Bedford, MA.

A liquid:liquid coalescer, may be used to remove residual oils from the aqueous layer. The coalescer enhances the collection of the oil droplets (the dispersed phase liquid) into larger droplets which will separate more easily from the aqueous layer (the continuous phase liquid).

Generally, for the subject application, a multiple stage system may be employed.

Such systems remove the designated materials in stages such as by first removing particulates. Once the particulates are removed the remaining liquid may then be treated with a coalescer to remove residual oil from the aqueous gelatin and glycerin.

A temperature of from about 300C to 70°C and a dilution volume of typically up to volumes, preferably from about 0.5 to 5 volumes of a suitable solvent, such as water, is desirable. Commercial coalescers are readily available such as those supplied by Millipore Corporation in Bedford, MA.

-17- WO 00/29097 PCTIUS99/27095 Filter aids containing diatomaceous earth can be employed for removal of particulates and/or residual oils. Diatomaceous earth, more commonly known as Celite or Filter Aid, is a very pure and inert material which forms a porous film or cake on a filter medium such as, but not limited to, filters made from paper, nylon and polypropylene as are typically used in filtration systems using filtration apparatus such as, but not limited to Nutsch filters, Rosenmund filters and/or centrifuges.

Diatomaceous earth can be employed: 1 by forming a slurry with an appropriate solvent, such as water, then filtering the slurry through an appropriate apparatus, such as a Nutsch or Rosenmund type filter, or a plate/coated plate filter such as a sparkler filter, to form a thin film or cake or 2) by adding the diatamaceous earth directly to the product to be filtered to form a slurry which is then filtered forming a porous thin cake or film. A temperature of from about 300C to 700C and a dilution volume of up to volumes, preferably from about 0.5 to 5 volumes of a suitable solvent, such as water, is desirable. Other filter aids besides diatamaceous earth include, but are not limited to silica, acrylic resins, clay and activated carbon.

Absorbents which may be used to treat the solvent based layers include zeolitic materials.

In particular, the lower aqueous phase may be heated, preferably hot filtered in the filtration assembly 18 if particulates and/or residual oils are present at a temperature -18- WO 00/29097 PCT/US99/27095 of approximately the same as above from about 30°C to 70C) preferably through liquid:liquid centrifugation or micro/sub-micro filtration as described above to remove any remaining traces of oily components or other contaminants through a conduit and optionally forwarded to the recycling system 8. Other types of filtration equipment which may be employed include plate filters, or coated plate filters like, for example, a sparkler filter. The preferred material of construction for these type of filters is stainless steel. Alternatively, nutche filters of the Rosenmund type or cartridge filters may be used for the purpose.

The employment of the hot filtration systems mentioned above separates particulates and/or oils from the aqueous layer containing gelatin and the softening agent glycerin).

Depending on the concentration of the gelatin and glycerin in the resulting filtrate, the filtrate may be returned directly to gelatin mass manufacturing or the filtrate may be transported via heated conduit 22 to a concentration assembly 16 which may be in the form of a diafiltration assembly and concentrated by removing some of the solvent water). For solutions having a gelatin concentration greater than about gelatin wt/wt 10% wtlwt to 45% wt/wt), the aqueous solution may be charged to a concentration apparatus adapted for vacuum distillation such as disclosed in Schmidt et al., U.S. Patent No. 5,288,408, or to a diafiltration system such as disclosed in Schmidt U.S. Patent No. 5,945,001 each of which is incorporated herein by -19- WO 00/29097 PCT/US99/27095 reference. Alternatively, the filtrate may be subjected to short path distillation as previously described.

Short path distillation for this aspect of the present invention is carried out under controlled conditions to facilitate the removal of water at a lower temperature to prevent thermal degradation of the recoverable gelatin. Evaporator temperatures typically from about 50°C to 120°C, and typically pressures 20 to 30 in. Hg, preferably 22-28 in. Hg are employed to remove water. Such temperatures and short contact time do not cause decomposition of the protein-based gelatin which affects its bloom strength. The water distillate is passed through a condenser to waste or recycle. The residue contains the gelatin/glycerin mixture for reuse.

As an example, waste gelatin material is diluted with solvent water) at a ratio of 3:1, water:waste gelatin material, the following illustrates the distillate:residue ratios which may be via the chosen distillation process, to achieve a desired level of recycled gelatin and glycerin.

To achieve a 25% recycle level for gelatin and glycerin from the above described 3:1 dilution, the distillation should preferably result in a distillate: residue ratio of 50:50.

To achieve a 40% recycle level for gelatin and glycerin from the above described 3:1 dilution, the distillation should preferably result in a distillate: residue ratio of 62.5:37.5.

In both examples the residue contains the gelatin and glycerin for recycle.

WO 00/29097 PCT/US99/27095 Diafiltration may be employed at the concentration assembly 16 to remove residual water soluble active ingredients, glycerine, water, and other water-soluble components such as preservatives and dyes and to provide gelatin in a form that is of sufficient purity and quality to permit reuse.

Diafiltration is a technique using ultrafiltration membranes to remove or fractionate different size molecules in macromolecular solutions. An ultrafiltration membrane retains macromolecules that are larger than the nominal molecular weight limit (NMWL) of the membrane and freely passes molecular species which are significantly smaller than the NMWL of the membrane. Macromolecules retained by the membrane are concentrated, while the low molecular weight species are removed.

Typically, the macromolecules must be "washed" using multiple wash volumes to remove residual smaller molecules, hence the name diafiltration filtration using ultrafiltration membranes and washing).

For continuous diafiltration, a supply of macromolecules gelatin) is added via the conduit 22 to the diafiltration assembly 16 at the same rate as the filtrate is being removed. This is also referred to as constant volume diafiltration. The concentration of the macromolecules does not change during the diafiltration process.

Discontinuous diafiltration involves first concentrating the macromolecule (e.g.

gelatin) batch to a predetermined volume, and then reconstituting the sample to its -21- WO 00/29097 PCT/US99/27095 original volume with replacement solvent. This is repeated until the smaller molecules are removed.

Referring to Figure 1 diafiltration may be accomplished by first heating the system from about 500C to 65*C by recirculating heated, deionized water typically for about 15 minutes through the conduit 24. The hot, aqueous feed stream is then pumped through he assembly 16 via a conduit 22 and concentrated to the desired gelatin/water concentration as discussed hereinafter. When the desired water/gelatin concentration is achieved, fresh, hot from about 50 to 650C), deionized water is fed into the system at exactly the same rate as the effluent exiting the system; the effluent being water and all water soluble components. Once the water soluble components have been removed, the remaining gelatin/water solution is recycled for gelatin encapsulation.

The filters that can be employed in the concentration/diafitration step are known and available in the art. Such filters include screen filters including open channel filters and the like. The selection of a suitable filter for the purification of gelatin must be capable of separating gelatin (typically having a molecular weight of from about 30,000 to 50,000) from smaller molecules.

The recovered aqueous gelatin solution is concentrated to a final solids (gelatin) concentration of at least between about 20% by weight, preferably from about 30% and WO 00/29097 PCT/US99/27095 The remaining concentrated gelatin is then purified using between about 1 and diafiltration volumes of water, preferably between about 3 and 10 diafiltration volumes to provide recovered gelatin that is sufficiently pure to permit reuse and which leaves the diafiltration assembly 16 via a conduit 26 to a receiver 34. A portion of the purified recycled gelatin may be sent back to the gelatin dissolving step via a conduit 28 to remove additional impurities from the gelatin to thereby obtain an even purer product.

Impurities such as dyes, actives, water, preservatives and glycerine can be removed from the diafiltration assembly via conduit Recovery of the above-mentioned impurities obtained from the diafiltration assembly 16 via the conduit can be performed in a recycling system 32. This system can be based on distillation systems including fractional distillation, short path distillation and reverse osmosis as previously described in connection with the recycle system 8.

Fractional distillation and reverse osmosis are preferred for recovery of the stream with reverse osmosis being the most preferred method.

The process stream 30 in addition to containing the above mentioned impurities may contain from about 1% to 10% by volume of glycerol in water, typically from about 3% to 7% by volume. The process stream 30 is treated at temperature of from about 0°C to 30°C, more typically from about 5°C to 20°C. Typically recovery of glycerol is at WO 00/29097 PCT/US99/27095 least 65% by volume, more typically from about 65% to 95%, most preferably from about 80% to 95% by volume.

In some instances, dyes and pigments that are used to color gelatin capsules have an affinity for the gelatin in the waste stream. Recovery of the gelatin alone may, therefore, require that steps be taken to eliminate this affinity so that the dyes can be removed. In general, it is necessary to take these steps following the hot filtration process and prior to the concentration/diafiltration process.

Suitable methods for eliminating the affinity between dyes and/or pigments and the gelatin include use of, for example, activated clay, carbon cartridge filtration; carbon slurry formation followed by filtration to remove the carbon; pH adjustment to eliminate adhesion of the dye to the gelatin, followed by direct diafiltration to remove the dyes, and then adjustment of the pH back to the normal processing pH from about 5 to or, a combination of these methods.

If an affinity exists between the dyes and/or pigments, once the affinity has been eliminated, diafiltration can be performed to obtain recovered gelatin. Alternatively, diafiltration itself will remove these dyes and/or pigments with sufficient diafiltration volumes. It is understood that the recycling system described can be incorporated into a conventional encapsulation apparatus to provide repeated or continual recycling of waste encapsulation materials.

-24- WO 00/29097 PCT/US99/27095 Entrapped air may be a consideration during the process of manufacturing gelatin mass for encapsulation into soft gelatin capsules. General practice in the soft gelatin capsule manufacturing industry is to manufacture the gelatin mass under vacuum, for the express purpose of removing air, on a mezzanine or second floor then feed the molten gelatin mass, by gravity, to the encapsulation machines on the first floor.

In the absence of a building configuration conducive to gravity feed to the encapsulation machines, gelatin mass can be transferred by air pressure or pumps.

The choice of pump must be such that as little air as possible is introduced into the gelatin mass. Examples of appropriate pumps may be, but are not limited to, peristaltic, moyno, and sine type pumps.

The ultrafiltration process of the present invention can generate flow rates in excess of 200 liters per minute. Although proper engineering and design of the diafiltration system will minimize or eliminate introduction of air from external sources, the flow rates generated may nonetheless, introduce some air into the gelatin. The air can be entrapped or dissolved in the viscous gelatin mass. Under these circumstances, it is desirable to degas or remove at least most of the air from the gelatin.

Typical practices in analytical chemistry for degassing dissolved air in water and/or organic solvents used as a mobile phase for High Performance Liquid WO 00/29097 PCT/US99/27095 Chromatography (HPLC) are: 1) pass the water and/or organic solvents through a 0.45 micron membrane filter and/or 2) sparge the water and/or organic solvent with an inert gas such as nitrogen and/or 3) allow the water and/or organic solvent to be exposed to molecular sieves until completely degassed.

It is also known in the art that microfilters are available commercially in the micron range similar to that used to degas mobile phase for HPLC analysis. Such filters may be obtained for example from A/G Technology of Needham, Massachusetts.

Any of the above-mentioned methods of degassing may be employed in the present invention. If, for example, a membrane filter 0.45 micron) were employed to degas the gelatin, the filter could be incorporated into the diafiltration system 16 shown in Figure 1. For example, the aqueous layer passing through the conduit 14 to the diafiltration system 16 is first treated as described above to remove impurities via the conduit 30. The recovered gelatin may then be filtered with a membrane filter to remove air within the diafiltration system 16.

In another embodiment of the present invention, the degassing operation may be established externally of the diafiltration system. Referring to Figure 2, the recovered gelatin is sent via the conduit 26 to a conduit 27 which leads to a degassing system 29 a membrane filter). Once the gas air) is removed from the gelatin, the degassed gelatin is sent via the conduit 31 to be recycled or recovered.

-26- WO 00/29097 PCT/US99/27095 It is understood that the above described recycling system may be incorporated into a conventional encapsulation apparatus to provide repeated or continual recycling of waste encapsulation materials.

Although the present invention has been described with reference to the particular embodiments herein set forth, it is understood that the present disclosure has been made only by way of example and that numerous changes in details of construction may be resorted to without departing from the spirit and scope of the invention. Thus, the scope of the invention should not be limited by the foregoing specifications.

Claims (24)

1. A method of treating a waste material containing gelatin comprising: a) combining the waste material and a solvent for the gelatin under sufficient conditions to form a first liquid containing gelatin, said waste material containing at least one first component which can not effectively be separated from the first liquid into a non-solvent based layer; b) separating the liquid into a solvent based layer containing the gelatin and said at least one component and a non-solvent based layer; and c) treating the solvent based layer with a process which removes the first component from the solvent based layer to form a second liquid containing gelatin having a higher purity than the first liquid being at least substantially devoid of the first component.

2. The method of claim 1 wherein the first component is selected from oily type materials, particulates and combinations thereof having an affinity for the solvent. 15

3. The method of claim 1 or claim 2 wherein step comprises treating the :°oooo solvent based layer with a process selected from the group consisting of liquid:liquid centrifugation, sub micro/microfiltration, coalescers, and combinations thereof.

4. The method of claim 3 wherein step comprises treating the solvent based layer with a tangential flow filter.

5. The method of any one of claims 1 to 4 wherein step is carried out at a temperature of from about 30 to

6. The method of claim 5 wherein the solvent based layer is diluted at a S"dilution volume of up to 5 volumes of said solvent. P

7. The method of any one of claims 1 to 6 wherein the waste material contains oily type materials and particulates, step comprising removing the oily type -29- materials and particulates from the solvent based layer to form a filtrate and recycling the filtrate.

8. The method of any one of claims 1 to 6 wherein the waste material contains oily type materials and particulates, step comprising removing the oily type materials and particulates from the solvent based layer to form a filtrate and treating the filtrate to remove at least some of the solvent.

9. The method of claim 8 wherein the step of treating the filtrate comprises subjecting the filtrate to a process selected from the group consisting of vacuum distillation, diafiltration and short path distillation..

10. The method of any one of claims 1 to 9 wherein the waste material contains a softening agent, said softening agent being separated into the second liquid.

11. The method of claim 10 wherein the softening agent is glycerin.

12. The method of claim 10 further comprising subjecting the second liquid to ultrfiltration to remove the softening agent therefrom. 15

13. The method of any one of claims 1 to 12 wherein the solvent is water. oooo

14. Apparatus for treating a waste material containing gelatin comprising: S• a) means for combining the waste material and a solvent for the gelatin under conditions sufficient to form a first liquid containing gelatin, said waste material containing at least one first component which can not effectively be separated from the first liquid into a non-solvent based layer; b) separation means for separating the first liquid into a solvent based layer containing the gelatin and said at least one first component and a non-solvent based layer; and c) treatment means for treating the solvent based layer to remove the first *component from the solvent based layer to form a second liquid containing gelatin having a higher purity that the first liquid and being at least substantially devoid of the first component.

The apparatus of claim 14 wherein the component is selected from oily type material, particulates and combinations thereof having an affinity for the solvent.

16. The apparatus of claim 14 or claim 15, wherein the treatment means is selected from the group consisting of liquid:liquid centrifugation, sub micro/microfiltration, coalescers, and combinations thereof.

17. The apparatus of claim 16 wherein the treatment means include a tangential flow.

18. The apparatus of any one of claims 14 to 17 wherein the waste material contains oily type materials and particulates, said treatment means comprising means for step removing the oily type materials and particulates from the solvent based layer to form a filtrate and recycling means for recycling the filtrate.

19. The apparatus of any one of claims 14 to 17 wherein the waste material 15 contains oily type materials and particulates, said treatment means comprising means for oooo 4: removing oily type materials and particulates from the solvent based layer to form a filtrate and means for treating the filtrate to remove at least some of the solvent.

The apparatus of claim 19 wherein the filtrate treating means is selected from the group consisting of vacuum distillation, diafiltration and short path distillation.

21. The apparatus of any one of claims 14 to 20 further comprising ultrafiltration means for treating the second liquid to remove any softening agent therefrom.

22. A waste material containing gelatin treated by a method according to any *A ST RA one of claims 1 to 13. -31

23. A method of treating a waste material containing gelatin, substantially as herein described with reference to any one of the embodiments of the invention as illustrated in the accompanying drawings and/or examples but excluding comparative examples.

24. Apparatus for treating a waste material containing gelatin, substantially as herein described with reference to any one of the embodiments of the invention as illustrated in the accompanying drawings and/or examples but excluding comparative examples. DATED this 6 th Day of March 2003 BALDWIN SHELSTON WATERS Attorneys for: A.B. TECHNOLOGIES, L.L.C. *9* 9*