MXPA95002526A - Porous particles aggregate and method for the same - Google Patents

Abstract

A porous aggregate is described that has an intra-aggregated reticular elevated volume for the free contention of functional substances. The porous aggregates comprise discrete particles, preferably of starch granules, jointly linked at least in their contact points in the aggregates. The surfaces of the discrete particles cooperate to define the intra-aggregated reticular volume. The porous aggregated composition of this invention finds use as high capacity carrier of functional substances for a wide variety of applications, where the functional substance is released of the aggregated composition under the influence of disintegration/mechanical compression by degrading or dissolving of the agglutinant components and/or particles or by diffusion from the porous surface.

Description

ADDED POROUS PARTICLES AND METHOD FOR THE SAME INVENTOR: ROY L. WHISTLER, citizen of the States United, residing at 320 Laurel Drive, West Lafayette, Indiana 47906, United States.

APPLICANT: FUISZ TECHNOLOGIES, LTD., A company of the United States, with address at 3810 Concorde Parkway, Suite 100, Chantilly, Virginia 22021, United States.

BACKGROUND AND SUMMARY OF THE INVENTION This invention relates to particulate carriers for functional substances. More particularly, this invention is directed to aggregates of particles having a high porosity and a large intra-aggregate crosslinked volume for containment of functional substances. The present aggregate compositions are manufactured economically to have predetermined release characteristics and other desired physical properties. There have been considerable research and development efforts aimed at the definition and manufacture of carriers for functional substances for a wide variety of commercial applications. The ideal carrier compositions are those that inherently exhibit a high capacity to carry / contain functional substances, those that function to increase or prolong the functionality of the substance contained or carried, and those that can be manufactured economically to meet the specifications unique ones required for each objective application. Such are the characteristics of the composition of the present invention. According to this invention, a porous, versatile, low cost composition is provided, which has a large volume of voids and therefore a high capacity for containing functional substances. The composition comprises free-flowing aggregates of discrete particles, most preferably starch granules, bonded together with a binder at their points of contact in the aggregate. The use of starch granules as the particle component of the present carrier composition provides surprisingly uniform spherical aggregates, ranging in diameter from about 15 to about 150 microns, depending on the size distribution of the component starch granules. The surfaces of the aggregated particles cooperate to define an intra-aggregate reticular volume for releasable containment of functional substances. Advantageously, the physical / chemical characteristics of the composition can be easily adjusted to meet the functional requirement of each target application by selection of the particle and agglutinating components. The aggregated compositions of particles according to this invention are prepared by forming a suspension of the particulate component in a solution of a binder and spray drying the resulting suspension using equipment and spray-drying technology recognized in the art. The particulate components can be pre-treated to promote their compatibility with the objective functional substance and to impart other properties such as hardness and solubility characteristics appropriate for the contemplated application of the carrier. In addition, the binder, typically a polymeric material that exhibits affinity for the particle component, can be selected according to its chemical and physical characteristics to optimize the functionality of the particulate aggregate as a carrier in an objective application. In this way, the binder component can be selected with a view to its solubility, its chemical reactivity, for example, its bioerodibility or biodegradability, as appropriate, to optimize the functionality of the particle aggregates of the invention. Finally, the present aggregated compositions can be coated to provide additional functionality. Functional substances can easily be introduced into the reticular volume of the porous aggregates herein.

The high intra-aggregate reticular volume and the high internal surface area of the aggregated compositions herein allow high loading of functional substances. The porous, charged aggregate compositions of this invention are free flowing powders that facilitate handling and mixing of the functional substance in product formulations and further provide a matrix for sustained or prolonged release of the functional substance carried. Additionally, it is contemplated that the aggregates of particles according to this invention exhibit functionality independent of their use as a carrier for functional substances. In this way, they can be used in prepared foods that require an earthy, diminutive character, either in mouthfeel or in appearance. The aggregate composition of particles according to this invention has utility in the areas of food / nutrition, the preparation of topical creams and lotions, deodorants / antiperspirants, cosmetics, agricultural products and products for human and veterinary medicine. For example, in a preferred embodiment, the aggregates of the invention can be included in a prepared food, such as a chewing gum. The compositions herein can be designed to enhance and prolong the functional characteristics of the contained functional compositions. Alternatively, the present composition may function to protect the contained functional substance from premature degradation. For example, pharmaceutical compositions administered orally may be formulated with / in the aggregated compositions, preferably the granular starch-based compositions of this invention, to provide an enteric formulation that functions to protect the active substance from the acidic / digestive conditions of the stomach and subsequently release the active substance in the small intestine. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the invention have been chosen for purposes of illustration and description, but are not intended in any way to restrict the scope of the present invention. Preferred embodiments of certain aspects of the invention are shown in the accompanying drawing, wherein: Figure 1 is an electron scanning photomicrograph of porous aggregates of particles prepared according to the invention. Detailed Description of the Invention In accordance with the present invention, a porous aggregate of discrete particles is provided. The particle components of the aggregates of the present typically have an average particle size of about 1 to about 100 microns in their largest dimension. The particles are bonded together with a binder, so that the surfaces of the aggregated particles cooperate to define an intra-aggregate reticular volume into which functional substances can be introduced. The contained substances are capable of being released from the aggregate for a period of time consistent with the diffusion of the functional substance contained in the surrounding environment with or without the co-operation of aggregate disintegration due to the solubilization or bioerosion / biodegradation of the binder components or particulate of the aggregate. The particulate aggregate composition of the present is prepared very easily and economically by suspending the particles in a solution of a suitable binder and subsequently drying the particulate suspension by spray using methodology and spray drying equipment recognized in the art. Optionally, the aggregate of particles can be further processed by applying a polymeric coating to the surface of the particulate aggregate after it is formed, either before or after a functional substance is introduced into the intra-aggregate reticular volume. The coating process can be carried out using spray coating equipment such as that used in a tablet manufacturing or fluidized bed type coating equipment., recognized in the subject. The discrete particles used in the preparation of the porous aggregates herein are preferably selected to have an average particle size of about 1 to about 100 microns, more preferably about 1 to 75 microns, in their largest dimension . Exemplary of such particulate material useful according to this invention are starch granules, particulate cellulosic materials such as micronized wood pulp or grain husks, and particulate polymeric materials such as those sold in the art as softeners for coating compositions, for example Pergopak polymer particles (registered trademark), sold by Martinswerk. Preferred particulate materials for use in accordance with this invention are granular starches, including native granular starches of various plant sources, such as corn, barley, rice and wheat, which are known for their somewhat larger starch granules, as well as vegetables known to produce small starch granules such as amaranth, quinoa, dasheen, neguilla, ash and Chinese taro. Particularly preferred for use in accordance with this invention are small starch granules such as those of amaranth and the fraction of wheat starch classified as small in size. Granular starches, presumably due to their inherent spherical or spheroidal structure, form substantially spherical granular starch aggregates when used as the particulate component of the aggregated compositions of the present invention. Optionally, the granular starch component of the preferred embodiments of the present composition may comprise chemically modified granular starches including granular starches which have been converted into microporous by undergoing partial hydrolysis with acid or enzymes. In addition, granular firmness and surface characteristics can be advantageously adjusted by pretreating the granules intended for use in the aggregate particulate compositions herein. In this way, for example, a greater degree of structural integrity and firmness can be introduced by pre-treating granular starch with an effective amount of a cross-linking chemical agent reactive with bifunctional starch. Any of the cross-linking starch agents recognized in the art may be used, including those recognized as acceptable for food by the Food and Drug Administration of the United States. Suitable crosslinking agents include phosphates such as sodium trimetaphosphate, dicarboxylic acid derivatives, particularly C2-C6 dicarboxylic acids, including maleic and glutaric acids, phosphorous oxychloride, epichlorohydrin, and beta, beta-dichlorodiethyl ether. Granular starches are made more resistant to mechanical damage, swelling and dissolution, with an increased degree of transverse linkage. In addition, the surface characteristics of the granular starches for use in the preparation of the particulate aggregates of the present invention, and thus the surface characteristics and absorption capacity of the resulting aggregates, can be affected by another type of modification. surface of the granular starch component. In this manner, granular starches intended for use in accordance with the present invention can be pre-treated with surface modifying agents to enhance the compatibility of the granules with functional substances contemplated as an objective for use with the porous particulate aggregate. If the substance to be introduced into the reticular volume of the aggregated particulate composition has a predominant lipid character, the starch granules can be treated to make their surface more lipophilic. In this way, the granules can be surface treated with solutions of amphiphilic polymers, or the surfaces of the granules can be chemically derived, for example by reacting the granules with sterile or octyl-succinic acid anhydride. The surfaces of the granules are thereby rendered more lipophilic and more compatible with functional substances having a predominant lipid character. The surface characteristics of the granular starch component of the compositions herein may also be modified for increased lipophilicity, by pre-treatment with stearification agents such as long-chain fatty acids or their derivatives, or by etherification with fatty halides long chain Treatment with acetic anhydride will also provide some lipophilic character to the granules, but a higher level of derivation is required. The particulate porous aggregates according to this invention are prepared by spray drying a slurry of particles in a solution of a binder component. The chemical nature of the binder is not critical, except insofar as the binder must exhibit some threshold affinity for the surface of the discrete particles so that it can operate to agglutinate aggregate particles together at least at its contact points during the process of spray drying. Also, inherently, the binder component must have some threshold solubility in the liquid used to suspend the particle component prior to the spray drying operation. That liquid is typically water; however, other liquids such as ether alcohols and ketones may also be employed, where the objective functionality of the particulate porous aggregate requires the use of a binder that does not have the threshold solubility in water. However, preferably, the particulate porous aggregates according to this invention are prepared by spray drying aqueous suspensions of discrete particles, preferably starch granules, suspended in an aqueous solution of a binder. There is a wide variety of suitable binders that can be used in the formation of the particulate aggregates herein. Almost typically, they are polymeric compositions that exhibit the required degree of liquid carrier solubility for the spray dried particulate suspension to form the porous aggregates. Polymeric materials can be water soluble, water insoluble, biodegradable / bioerodible, non-biodegradable, natural, synthetic or semi-synthetic; the binder to be selected for any particular application depending on the desired functionality, the desired chemical / physical stability, and the desired release characteristics of the objective aggregate according to this invention. Preferred binders for use in accordance with this invention are biodegradable polymers such as polysaccharides, including gums such as guar and locust bean gums, pectins, agar, alginate, gelatin, dextrins, dextran and derived starches and cellulosic materials such as carboxymethyl cellulose , hydroxymethyl cellulose, hydroxypropyl cellulose, and the like, proteins, particularly proteins other than those endogenous to the starch granules used to form the aggregates, and polyesters. Polysaccharides are preferred binders for use in accordance with the present invention. The binder components can also be non-biodegradable, synthetic or semi-synthetic polymers, such as polyvinyl alcohol, poly-N-vinyl-2-pyrrolidone, and polymers or copolymers of acrylic or methacrylic acid and their amide derivatives, including polyacrylamide. According to the embodiment relating to the method of the present invention, porous aggregates of discrete particles are prepared by spray drying a suspension of such particles in a solution of a suitable binder using conventional spray drying equipment and conditions. One limitation of the spray drying process is the stability of the particulate component. Specifically, when granular starch suspensions are spray-dried in aqueous binder solutions, it is much preferred that the temperature of the spray-drying operation not be so high as to effect gelatinization of the starch granules. The binder component is typically functional at extremely low levels, most preferably from about 0.1 to about 2% by weight of the solution / suspension. The particulate component usually constitutes between about 2 and about 20% by weight of the suspension prepared for spray drying according to this invention to produce the particulate porous aggregates herein. The aggregate, porous, particulate composition according to this invention exhibits physical and chemical characteristics dependent on the discrete particles and constituent binder component. The aggregates vary in size from about 10 to about 250 microns, more typically between about 15 and 150 microns, most typically between about 10 and about 50 microns. The size and shape of the particle aggregates of the present depend significantly on the shape and particle size distribution of the discrete particles. In this way, when the preferred particle component - starch granules - is used to form the porous aggregates of the present, the aggregates assume a remarkably spherical shape, uniform with the individual granules bonded together with the binder components at their contact points. The surfaces of the aggregated starch granules cooperate to define an intra-aggregate reticular volume for releasable containment of a functional substance. The size, shape and particle size distribution of the porous aggregates in particles prepared according to this invention also depend on the conditions selected for the spray drying operation. However, the conventional spray-drying parameters used to form the starch granules-based aggregates preferred according to this invention produce surprisingly uniform porous, spherical aggregates. The porous, particulate aggregate composition of the present invention is advantageously used as a carrier for a wide range of functional substances. The term "functional substances", as used herein to describe the present invention, refers to any compound or composition that inherently possesses biological activity or other functional activity and exhibits such activity to achieve some useful result when applied or used. in a form adapted to take advantage of such activity. Examples of such substances that can be absorbed into the intra-aggregate reticular volume of such aggregates according to such invention are salad oils, flavors, insect repellents, insecticides, herbicides, perfumes, humectants, soaps, anti-perspirants, waxes, creams. and lotions for the body, fertilizers, minerals, vitamins, bacteriostats and therapeutic drug substances. Salad oils such as hydrogenated or partially hydrogenated vegetable oils are useful as functional substances in the present invention and include materials such as corn oil, canola oil, rapeseed oil, cottonseed oil, sesame oil, oil soy bean, grape seed oil, sunflower oil, safflower oil, olive oil, peanut oil and the like. A wide variety of flavors may be included as functional substances in the present invention. The term "flavors" as used herein includes natural and synthetic flavoring materials, as well as sweeteners. An illustrative list of such agents includes volatile oils, synthetic flavor oils, aromatic flavors, oils, liquids, oleoresins or extracts derived from plants, leaves, flowers, fruits, stems and combinations thereof. A representative, non-limiting list of examples include citrus oils such as lemon, orange, grape, lime and grapefruit and fruit essences that include flavors of apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot or other fruit flavors. Other useful flavorings include aldehydes and esters such as benzaldehyde (cherry, almond), citral, ie alpha-citral (lemon, lime), neral, ie beta-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2-6-dimethyloctanal (green fruits) and 2-dodecenal (citrus, mandarin), their mixtures and the like. Useful sweeteners may be selected from the following non-limiting list: glucose (corn syrup), dextrose, invert sugar, fructose and mixtures thereof; saccharin and its various salts, such as sodium salt; dipeptide sweeteners such as aspartame; compounds of dihydrochalcone, glycyrrhizin; Stevia rebaudiana (stevioside); chlorinated derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol and the like. Also contemplated are the hydrogenated starch hydrolysates and the synthetic sweetener 3,6-dihydro-6-methyl-III, 2,3-oxathiacin-4-one-2,2-dioxide, particularly the potassium salt (acesulfama-K). ), and its sodium and calcium salts. Other sweeteners may also be used. The substances of therapeutic drugs that can be used as functional substances in the present invention are varied. A non-limiting list of such substances is as follows: anti-tresses, anti-histamines, decongestants, alkaloids, mineral supplements, laxatives, vitamins, antacids, ion-exchange resins, anti-cholesterol, anti-lipid agents, anti-arrhythmic agents , antipyretics, analgesics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral dilators, anti-infective, psychotropic, anti -manic, stimulants, gastrointestinal agents, sedatives, anti-diarrhea preparations, anti-anginal drugs, vasodilators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, anti-biotic, tranquilizers, anti-psychotic, anti-tumor drugs, anti -coagulants, antithrombotic drugs, hypnotics, anti-emetieos, anti-nausea agents, anti-convulsants, neuromuscular drugs, age hyper and hypoglycemic drugs, thyroid and anti-thyroid preparations, diuretics, anti-spasms, uterine relaxants, mineral and nutritional additives, anti-obesity drugs, anabolic medications, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, anti-drugs -uricémicos and their mixtures. Especially preferred active ingredients contemplated for use in the aforementioned enteric formulations of the present invention are the anti-acids, H2 antagonists and analgesics. For example, anti-acid doses can be prepared by using the ingredient calcium carbonate alone or in combination with magnesium hydroxide and / or aluminum hydroxide. Moreover, anti-acids can be used in combination with H2 antagonists. Analgesics include aspirin, acetaminophen, acetaminophen plus caffeine, and ibuprofen. Such functional substances can be absorbed or otherwise introduced into the porous aggregates of the present invention either by spraying solutions of such substances onto the prepared aggregates, adding such substances to the particle slurries prior to the spray drying process, or adding the added to solutions of said substances where the solvent for such substances is selected so as not to dissolve prematurely or otherwise disturb the aggregate binder component. The produced aggregates containing functional substances within the reticular volume defined by the surfaces of the aggregated particles can be isolated in the process using techniques recognized in the art, such as filtration, centrifugation, air classification and drying. The degree of loading of the functional substances in the porous aggregates can be controlled in part by adjusting the concentration of the functional substance in the solutions used to load the aggregate matrices. Higher concentrations of the charged material can be achieved by using more concentrated solutions of the substances and repeating the charging procedure. Preferably, the substances are introduced into the particulate porous aggregates either as a component of the spray dried slurry or slurry, used to form the aggregates, or as a solution in an inert, relatively low boiling solvent., which can be removed by evaporation after loading the aggregate matrix. A hydrophobic liquid, such as a flavor oil, can be loaded into the aggregate, simply by allowing the oil to soak in the porous aggregate. The release characteristics and other physical properties of the particulate aggregates according to this invention may be further modified by coating the aggregates after their preparation with a solution of a coating composition which may be the same as or different from the binder / polymer. The coating operation is preferably carried out after the loading of the aggregates with the desired functional substance. The coating operation can be achieved by simply spraying the porous aggregate, particulate composition with a dilute solution of a coating composition which may be the same as or different from that used as the binder component of the aggregate composition. The coating operation can be conducted in spray-type coating equipment such as that used for conventional tablet coating operations or in conventional fluidized bed type coating equipment. Other conventional operations include tray coating processes, spray coating processes, and drum coating processes. The coating composition used in the optional aggregate coating operation can be selected to optimize the objective functionality of the aggregate carrier composition. Suitable coating compositions include any of the aforementioned as binder components as well as other coating compositions recognized in the art, used in conventional tablet coating applications. Other coating compositions recognized in the art include coating materials such as film-forming materials. Film-forming materials, such as fats, natural resins, natural polymeric materials, and synthetic polymeric materials, are included as coating materials according to the invention. A non-limiting list of suitable types of coating materials includes: melted coating materials such as partially hydrogenated cottonseed oil, partially hydrogenated palm oil, partially hydrogenated soybean oil, partially hydrogenated castor oil, beeswax , carnauba wax, polyethylene glycol, paraffin, esters of long chain alcohols, gelatin / wax materials, and gelatin / grasa materials; polymers in aqueous polymer dispersion, such as L30D (copolymethacrylic acid / ethylacrylate), RS / RL30D (copolyethylacrylate / methyl methacrylate / trimethylammonium ethyl methacrylate chloride), NE30D (copolyethylacrylate / methyl methacrylate / ethyl cellulose), Sureloase (ethylcellulose), EC Aquateric (ethyl cellulose / cellulose acetate phthalate), Coateric (polyvinyl acetate), and Coateria (polyvinyl acetate phthalate / hydroxypropyl methyl cellulose acetate succinate); and solvent coating polymers such as methyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, cellulose acetate, cellulose triacetate, butyrate? of cellulose acetate, cellulose acetate phthalate, cellulose acetate trimethylate, carboxymethyl cellulose, hydroxypropyl methylcellulose phthalate, methacrylic acid polymers and copolymers, and methacrylate polymers and copolymers. Porous particulate aggregates according to this invention can be used, without added functional substances, as a thickening agent or to impart other desirable organoleptic characteristics, such as mouthfeel, in various prepared foods. However, preferably, the compositions herein are used as a carrier and excipient for functional substances to enhance or prolong the functionality of the substance. Thus, for example, the present composition can be used as a carrier for functional liquids, essentially by converting them into free-flowing powders that can be used as substitutes for such functional substances in compositions to promote and / or to prolong functionality of the substance. The functional substances carried or contained are released from the particulate porous aggregate by simple diffusion, or when mechanical compression or chemical degradation or simple dissolution of the binder and / or particle components occurs. For example, it has thus been found that the granular starch aggregates according to this invention using a guar gum or carboxymethyl cellulose binder can be "loaded" with a flavor oil and used as a chewing gum component. to prolong the flavor release. The following examples are presented to illustrate the present invention and should not be construed in any way as a limitation thereof. Example 1 A slurry of amaranth starch granules is formed in a solution of about 0.5 to about 1% by weight of a high viscosity, commercial guar gum to produce spherical, resistant aggregates. The spherical aggregates range from about 10 to about 30 microns in diameter. Example 2 A slurry of granular amaranth was suspended in a 0.1% guar gum solution and spray dried to produce spherical aggregates having a size range of about 10 to about 30 microns. The aggregates were dispersed in peppermint oil, centrifuged and then washed with ethanol in a glass pipette and dried to provide an added composition loaded with peppermint oil containing about 35% by weight of peppermint oil. The aggregate composition of starch loaded with peppermint oil was then spray coated with a 0.5% solution of guar gum. The coated spheres were essentially odorless, but they released peppermint oil and odor when rubbed on a glass plate with a metal spatula. EXAMPLE 3 A slurry of rice starch in a 1% aqueous solution of locust bean gum is spray-dried to produce porous spherical aggregates having a high intra-aggregate reticular volume. EXAMPLE 4 The small granular fraction of wheat starch obtained by size classification of native wheat starch is formed into a slurry in an aqueous medium containing methylhydroxypropyl cellulose of medium viscosity and spray-dried to produce substantially spherical aggregates of small starch granules. wheat. The aggregates are dispersed in mint oil, centrifuged and then washed with ethanol in a glass pipette and dried to provide an aggregate composition loaded with peppermint oil containing about 48% by weight of peppermint oil. The added composition of starch loaded with peppermint oil is then spray coated with a 0.5% gelatin solution. The coated spheres were essentially odorless, but they released peppermint oil and odor when rubbed on a glass plate with a metal spatula. Example 5 A suspension of 10 g of micronized wood pulp having an average particle size of from about 5 to about 150 microns in 150 ml of ethanol containing 1.5% by weight of poly-N-vinyl pyrrolidone is spray-dried a conventional spray dryer to produce porous aggregates. The aggregate composition is dispersed in an aqueous solution of a pesticide, filtered and dried to provide a particulate, pesticide-laden, particulate composition according to this invention. EXAMPLE 6 A slurry of rice starch is formed in a 0.1% solution of guar gum and spray dried to produce a free-flowing powder comprising spherical aggregates of about 30 microns in diameter. The aggregates are non-hygroscopic and maintain their spherical shape under normal processing. The disintegration of the rice starch aggregates in water occurs during a period of time during which the inter-granular gum dissolves to allow the disintegration of the spheres. Example 7 Commercial corn starch is dispersed in a 0.1% by weight solution of carboxymethyl cellulose and spray dried to result in aggregates of granular corn starch according to this invention. Example 8 Rice starch is suspended for 5 minutes in a 0.2% starch dextrin solution of 20 DE (dextrose equivalent) and spray dried with a spray nozzle reading of 120 ° C to produce well-defined spherical aggregates of rice starch. Example 9 Granules of amaranth starch are suspended in a 0.1% solution of sodium alginate and dried by spray to form a granular aggregate bonded by means of alginate. The product is sprayed or briefly washed with 1% calcium chloride solution to convert the sodium alginate binder into water insoluble calcium alginate. The resulting spheres exhibit increased stability under aqueous conditions up to temperatures close to the gelatinization temperature of the starch component. The spheres are spray-coated with a 1% solution of sodium alginate and then sprayed with calcium chloride solution to increase physical stability and water resistance. Spheres coated with calcium alginate and filled with peppermint oil are stabilized with respect to oil leakage from the aggregate composition.

EXAMPLE 10 Aggregates of amaranth and wheat starch formed with carboxymethyl cellulose binder or locust bean gum are incorporated at a rate of 2% by weight in an ice-cream composition prepared with only 50% of the normal fat content, without compromising the taste and the sensation in the mouth. EXAMPLE 11 The small granular fraction of wheat starch is formed into a slurry in an aqueous solution of 0.1% gelatin and spray dried to produce porous, substantially spherical aggregates. The aggregate composition is formed into a slurry in an alcoholic solution of an orally effective antibiotic, then filtered and dried. The dry aggregates are coated in a fluidized bed coating machine with a 0.5% ethyl cellulose solution of the type used for tablet coating. The coated aggregates are filled into capsules for oral administration.

Claims (30)

1. CLAIMS 1. A composition of matter comprising porous, substantially spherical aggregates of starch granules bonded together with a binder at least at their contact points in said aggregates, the surface of said aggregated starch granules cooperating to define an intra-reticular volume. added for releasable containment of a functional substance, said aggregates of starch granules having an average diameter of about 5 to about 250 microns.
2. 2. The aggregate composition of starch granules of claim 1, wherein the binder comprises a water-soluble polymer not endogenous to the starch granules.
3. 3. The aggregate composition of starch granules of claim 1, further comprising a coating composition applied to the surface of the aggregates.
4. 4. The aggregate composition of starch granules of claim 1, wherein the starch granules comprise microporous, partially hydrolyzed starch granules.
5. The aggregate composition of starch granules of claim 1, wherein the binder is a biodegradable or bioerodible polymer selected from the group consisting of polysaccharides and proteins not endogenous to the starch granules and polyesters.
6. 6. The aggregate composition of starch granules of claim 1, further comprising a functional substance in the lattice volume of the porous aggregates.
7. The aggregate composition of starch granules of claim 6, wherein said functional substance comprises a therapeutic drug substance.
8. 8. The aggregate composition of starch granules of claim 6, further comprising a coating composition applied to the surface of the porous aggregates.
9. 9. The aggregate composition of starch granules of claim 1, wherein said composition is a prepared food.
10. 10. The aggregate composition of starch granules of claim 9, wherein said prepared food is a chewing gum.
11. 11. A method for preparing porous aggregates of discrete particles having an average particle size of about 1 to about 100 microns in their largest dimension, said aggregated particles linked together to the discrete particles at least at their contact points in said added, said method comprising the steps of forming a suspension of said particles in a solution of the binder and spray drying said suspension.
12. The method of claim 11, further comprising the step of applying a coating composition to the surface of the porous aggregates.
13. The method of claim 11, wherein the binder is a water soluble polymer.
14. The method of claim 11, further comprising the step of introducing a functional substance into the crosslinked volume of the porous aggregate.
15. 15. The method of claim 14, wherein said functional substance comprises a therapeutic drug substance.
16. 16. The method of claim 14, further comprising the step of applying a polymer solution to coat the surface of the porous aggregate.
17. 17. The method of claim 11, wherein the discrete particles are starch granules.
18. 18. The method of claim 12, wherein the discrete particles are starch granules.
19. 19. The method of claim 4, wherein the discrete particles are starch granules.
20. The method of claim 16, wherein the discrete particles are starch granules.
21. 21. A composition of matter comprising an aggregate of discrete particles, said particles having an average particle size of about 1 to about 100 microns in their largest dimension, said particles linked together with a binder not endogenous to the particles at less at their points of contact in said aggregate, the surfaces of said aggregate particles cooperating to define an intra-aggregate reticular volume adapted for releasable containment of functional substances.
22. 22. The aggregate particle composition of claim 21, where the discrete particles comprise starch granules.
23. 23. The aggregate particle composition of claim 21, wherein the particles comprise micronized cellulose pulp.
24. 24. The aggregate particle composition of claim 21, wherein the particles comprise synthetic polymer particles.
25. 25. The aggregate particle composition of claim 21, further comprising a functional substance in the reticular volume.
26. 26. The aggregate particle composition of claim 25, wherein said functional substance comprises a therapeutic drug substance.
27. 27. The aggregate particle composition of claim 25, further comprising a coating composition applied to the surface of the aggregate.
28. The aggregate particle composition of claim 27, wherein the coating composition is selected from the group consisting of a polysaccharide, a polyvinyl alcohol, a poly-N-vinyl-2-pyrrolidone, a polyacrylamide, and a polymer or copolymer acrylic.
29. 29. The aggregate particle composition of claim 21, wherein the binder is a biodegradable polymer.
30. 30. The aggregate particle composition of claim 29, wherein the polymer is selected from the group consisting of polysaccharides, proteins and polyesters.