| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | August 1, 2000 |
| PATENT TITLE |
Bioerodible porous compositions |
| PATENT ABSTRACT | A composition for the sequestration and sustained delivery of an active ingredient in the form of porous particles, the composition comprising the product of the controlled dehydration of particles formed by the reaction of a polymeric anionic material with a polyvalent cation. The composition may be loaded with an active ingredient by soaking the particles in a solution of the active ingredient; and may then be dehydrated. They may then be soaked in a solution of a polymeric cationic material, to form particles providing the controlled release of the active ingredient |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | February 24, 1997 |
| PATENT REFERENCES CITED |
M. Daly et al., "Chitosan-Alginate Complex Coacervate Capsules: . . . ", Biotech. Progress, 4(2), 76-81 (1988). T. Hayashi, "Polymer Microspheres as Carriers of the Immobilized Enzymes", Makromol. Chem., Macromol. Symp., 70/71, 137-145 (1993). Y. Kikuchi et al., "Permeability Control of Polyelectrolyte Complex Membrane . . . ", Bull. Chem. Soc. Jpn., 61, 2943-2947 (1988). E. Kokofuta et al., "Use of Polyelectrolyte Complex-Stabilized Calcium Alginate Gel . . . ", Biotech. Bioeng., 32, 756-759 (1988). S. Kyotani et al., "A Study of Embolizing Materials for Chemo-embolization Therapy . . . ", Chem. Pharm. Bull., 40(10), 2814-2816 (1992). Y.P. Li et al., "Preparation of Chitosan Microspheres Containing Fluorouracil . . . ", S.T.P. Pharma Sci., 1(6), 363-368 (1991). Y. Nishioka et al., "Preparation and Release Characteristics of Cisplatin Albumin Microspheres . . . ", Chem. Pharm. Bull., 37(11), 3074-1077 (1989). Y. Nishioka et al., "A Study of Embolizing Materials for Chemo-Embolization Therapy . . . ", Chem. Pharm. Bull., 40(1), 267-268 (1992). Y. Ohya et al., "Thermo-sensitive Release Behavior of 5-Fluorouracil from Chitosan-Gel . . . ", J. Bioact. Comp. Polymers, 7, 242-256 (1992). T. Ouchi et al., "Release Behavior of 5-Fluorouracil from Chitosan-Gel Microspheres . . . ", [Journal, vol., and date unknown], 360-361. T. Sakiyama et al., "Preparation of a Polyelectrolyte Complex Gel from Chitosan . . . ", J. Appl. Poly. Sci., 50, 2021-2025 (1993). L. Szosland et al., "Production of Biocide-Containing Polymer Microspheres . . . ", Int. Poly. Sci. Tech., 20(6), T/87-T/93 (1993). B.C. Thanoo et al., "Cross-linked Chitosan Microspheres . . . ", J. Pharm. Pharmacol., 44, 283-286 (1992). H. Tomida et al., "A Novel Method for the Preparation of Controlled-Release Theophylline . . . ", Chem. Pharm. Bull., 42(4), 979-981 (1994). T. Sato et al., "Porous-Biodegradable Microspheres for Controlled Drug Delivery . . . ", Pharm. Res., 5, 21-30 (1988). A. Supersaxo et al., "Preformed Porous Microspheres for Controlled and Pulsed Release . . . ", J. Control. Rel., 23, 157-164 (1993). C. Yan et al., "Dependence of Ricin Toxoid Vaccine Efficacy . . . ", Vaccine, 13, 645-651 (1995). T.L. Bowersock et al., "Oral Vaccination with Alginate Microsphere Systems", J. Control. Rel., 39, 209-220 (1996). E.C. Downs et al., "Calcium Alginate Beads as a Slow-Release System . . . ", J. Cell. Physiology, 152, 422-429 (1992). M.A. Wheatley et al., "Coated Alginate Microspheres: . . . ", J. Appl. Poly. Sci., 43, 2123-2125 (1991). L.-S. Liu et al., "Controlled Release of Interleukin-2 . . . ", J. Control. Rel., 43, 65-74 (1997). J. Heller et al., "Alginate/Chitosan Microporous Microspheres for the Controlled Release of Proteins and Antigens", Pro. Intern. Symp. Control. Rel. Bioact. Mater., 23 (#351) 269-270 (1996). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A time-release delivery vehicle in the form of porous micropheres for the sequestration and sustained delivery of an active ingredient, the vehicle comprising the product of the controlled dehydration of microsperes formed by the reaction of a polymeric anionic material with a polyvalent cation. 2. The vehicle of claim 1 where the polymeric anionic material is selected from the group consisting of alginate, polyvinyl alcohol, galactan sulfate, polyacrylic acid, gum arabic, and polyphosphagine. 3. The vehicle of claim 1 where the polyvalent cation is calcium ion. 4. The vehicle of claim 1 where the micropheres have a diameter from about 1 micron to about 1000 microns. 5. A method of preparing a time-release delivery vehicle for the sequestration sustained delivery of an active ingredient, the method comprising: (a) forming a plurality of micropheres by the dispersion of droplets of a solution of a polymeric anionic material into a solution of a polycation; and (b) dehydrating the micropheres by controlled dehydration. 6. A method of preparing a time-releasing delivery composition containing an active ingredient for the sustained delivery of that active ingredient, the method comprising: (a) forming a plurality of micropheres by the dispersion of droplets of a solution of a polymeric anionic material into a solution of a polyvalent cation; (b) dehydrating the micropheres by controlled dehydration; (c) loading the micropheres with the active ingredient by soaking the micropheres in a solution cintaining the active ingredient; (d) drying the resulting loaded micropheres; (e) soaking the loaded micropheres in a solution of a polymeric cationic material; and (f) drying the resulting micropheres. 7. The method of claim 6 where the polymeric anionic material is selected from the group consisting of alginate, polyvinyl alcohol, galactan sulfate, polyacrylic acid, gum arabic, and polyphosphagine. 8. The method of claim 6 where the polyvalent cation is calcium ion. 9. The method of claim 6 where the polymeric cationic material is selected from the group consisting of chitosan, polylysine, and polyarginine. 10. The method of claim 6 where the active ingredient is a protein or peptide. 11. The method of claim 6 where the micropheres have a diameter from about 1 micron to about 1000 microns. 12. The method of claim 6 where the polymeric anionic material is alginate and the polymeric cationic material is chitosan. 13. The method of claim 5 where the polymeric anionic material is selected from the group consisting of alginate, polyvinyl alcohol, galactan sulfate, polyacrylic acid, gum arabic, and polyphosphagine. 14. The method of claim 5 where the polyvalent cation is calcium ion. 15. The method of claim 5 where the micropheres have a diameter from about 1 micron to about 1000 microns. 16. A time-release delivery composition containing an active ingredient for the sustained delivery of that active ingredient, the composition comprising the product of the method of claim 7. 17. The method of claim 16 where the micropheres have a diameter from about 1 micron to about 1000 microns. 18. The composition of claim 16 where the active ingredient is a protein or a peptide. 19. A time-release delivery vehicle in the form of porous micropheres for the sequestration and sustained delivery of an active ingredient, the vehicle comprising the product of the lyophilization of microspheres formed by the reaction of a polymeric anionic material with a polyvalent cation. 20. The vehicle of claim 19 where the polymeric anionic material is selected from the group consisting of alginate, polyvinyl alcohol, galactan sulfate, polyacrylic acid, gum arabic, and polyphosphagine. 21. The vehicle of claim 19 where the polyvalent cation is calcium ion. 22. The vehicle of claim 19 where the microspheres have a diameter from about 1 micron to about 1000 microns. 23. A method of preparing a time-release delivery vehicle for the sequestration and sustained delivery of an active ingredient, the method comprising: (a) forming a plurality of microspheres by the dispersion of droplets of a solution of a polymeric anionic material into a solution of a polycation; and (b) lyophilizing the microspheres. 24. The method of claim 23 where the polymeric anionic material is selected from the group consisting of alginate, polyvinyl alcohol, galactan sulfate, polyacrylic acid, gum arabic, and polyphosphagine. 25. The method of claim 23 where the polyvalent cation is calcium ion. 26. The method of claim 23 where the microspheres have a diameter from about 1 micron to about 1000 microns. 27. A method of preparing a time-release delivery composition containing an active ingredient for the sustained delivery of that active ingredient, the method comprising: (a) forming a plurality of microspheres by the dispersion of droplets of a solution of a polymeric anionic material into a solution of a polyvalent cation; (b) lyophilizing the microspheres; (c) loading the microspheres with the active ingredient by soaking the microspheres in a solution containing the active ingredient; (d) drying the resulting loaded microspheres; (e) soaking the loaded microspheres in a solution of a polymeric cationic material; and (f) drying the resulting microspheres. 28. The method of claim 27 where the polymeric anionic material is selected from the group consisting of alginate, polyvinyl alcohol, galactan sulfate, polyacrylic acid, gum arabic, and polyphosphagine. 29. The method of claim 27 where the polyvalent cation is calcium ion. 30. The method of claim 27 where the polymeric cationic material is selected from the group consisting of chitosan, polylysine, and polyarginine. 31. The method of claim 27 where the active ingredient is a protein or peptide. 32. The method of claim 27 where the microspheres have a diameter from about 1 micron to 1000 microns. 33. The method of claim 27 where the polymeric anionic material is alginate and the polymeric cationic material is chitosan. 34. A time-release delivery composition containing an active ingredient for the sustained delivery of that active ingredient, the composition comprising the product of the method of claim 29. 35. The composition of claim 34 where the microspheres have a diameter from about 1 micron to about 100 microns. 36. The composition of claim 34 where the active ingredient is a protein or a peptide. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION This invention relates to bioerodible porous compositions for the sequestration and sustained delivery of active agents, particularly pharmaceutical active agents. Successful treatment of a variety of conditions is limited by the fact that agents known to effectively treat these conditions may have severe side effects, requiring low dosages to minimize these side effects. In other instances, the therapeutic agents may be very labile, or have very short half-lives requiring repeated administration. In still other instances, the long term administration of a pharmaceutical agent may be desired. In all these cases, the ability to deliver a controlled dosage in a sustained fashion over a period of time may provide a solution. One method of doing so that has received a fair amount of attention is the sequestration and subsequent controlled release of active agents into and from porous compositions. A number of publications describe the use of nondegradable porous microbeads. For example, U.S. Pat. No. 4,690,825 to Won describes delivery vehicles comprised of a polymeric bead, preferably made of polystyrene, or poly(methyl methacrylate) having a rigid, substantially non-collapsible network of pores with an active ingredient held within the network, for use in a method to provide controlled release of the active ingredient. The delivery vehicles can be polymerized by a process in which the active ingredient also comprises the porogen during formation of the network of pores. The beads may be dried to obtain a powder-like substance comprised of beads which retain the porogen within the network of pores. U.S. Pat. No. 5,145,675 to Won describes the use of a porogen in the preparation of polymer beads preferably made of polystyrene, or poly(methyl methacrylate) having a rigid, substantially non-collapsible network of pores. Active agents are then diffused into the porous beads from an external solution. However, both of these compositions are nondegradable and are thus only useful in topical applications where removal is not necessary. Clearly, for systemic applications where porous microparticles are implanted in an appropriate body site it is essential that the polymer microspheres be biodegradable. Heretofore, major activity in the development of biodegradable microspheres has been concentrated on porous microspheres constructed from lactide/glycolide copolymers as described by Sato et al.(1988), Pharm. Res. 5: 21-30, or by Supersaxo et al. (1993), J. Controlled Release 23, 157-164. However, the preparation of these hollow microspheres requires the use of organic solvents such as methylene chloride which must be subsequently removed so that only a few parts per million remain, a very difficult task. Also, the bioerosion of lactide/glycolide copolymers is relatively slow. Further, even though lactide/glycolide copolymers have obtained FDA approval for certain uses, they are not GRAS ("generally regarded as safe") materials and for this reason, extensive toxicological studies are necessary before new uses are approved. Thus, there exists a need to develop bioerodible, porous compositions that can be prepared in an aqueous environment, into which sensitive therapeutic agents can be easily and reproducibly incorporated and from which they can be released in an active state. It is further desirable that the materials used to make the compositions be GRAS ("generally regarded as safe") materials. Although there has been no reported work dealing with preparation of porous microspheres that can be prepared in an aqueous environment, there has been a great deal of work on solid porous particles that can be prepared in an aqueous environment. That work can be generally divided into work dealing with the incorporation of living cells, and work dealing with the incorporation of antigens and proteins. U.S. Pat. No. 5,116,747 to Moo-Young et al. describes the immobilization of cells and other biologically active materials within a semipermeable membrane or microcapsule composed of an anionic polymer such as alginate induced to gel in the presence of calcium and/or a polymeric polycation such as chitosan. U.S. Pat. No. 4,663,286 to Tsang et al. describes the encapsulation of solid core materials such as cells within a semipermeable membrane, by suspending the core material in a solution of a water-soluble polyanionic polymer, preferably alginate salts, forming droplets, and gelling the polyanion with a polyvalent polycation such as a polypeptide, a protein or a polyaminated polysaccharide, preferably polylysine, polyarginine, or polyornithine. This patent further teaches controlling the porosity and permeability of the disclosed compositions to molecules ranging from about 60,000 to about 900,000 daltons by changing the degree of hydration of the polymer. Incubation in saline or chelating agents increases hydration and expands the gels, whereas incubation in calcium chloride contracts the gel mass. Increases in charge density of the polycationic membrane generally produces smaller pores. Increases in the molecular weight of the polycationic polymer generally produce a thicker, less permeable membrane. U.S. Pat. No. 4,803,168 to Jarvis describes the encapsulation of core materials such as cells, enzymes, antibodies, hormones, etc. within a semipermeable membrane or microcapsule composed of an aminated polymeric inner layer such as chitosan ionically bound to an anionic polymeric outer layer such as polyglutamic or polyaspartic acid, and having a porosity of about 80,000 daltons. A number of publications describe the incorporation of antigens and proteins into calcium alginate microparticles. For example, Bowersock et. al. (1996), J. Controlled Release 39: 209-220, describe development of oral vaccines using an alginate microsphere system and Downs et. al. (1992), J. Cell. Physiol. 152: 422-429 describe the release of growth factors from calcium alginate beads. However, entrapment efficiency was very low and typically, more than 90% of the active agent is not incorporated. Because many of these agents are very expensive, and in some cases high concentration of the active agent in the microsphere is desired, improved methods for preparing drug-loaded microspheres are needed. A publication by Wheatley et. al. (1991), J. Appl. Polymer Sci., 43: 2123-2135, describes a method for improving entrapment efficiency in alginate/polycation nicrospheres. In this method a diffusion-filling technique is used where blank calcium alginate beads are coated twice with small amounts of a polycation and protein then loaded into these capsules by stepwise diffusion from solutions of increasing drug concentration. This is then followed by a final coating with a polycation. This is a laborious and time-consuming process that requires a number of steps, i.e. empty alginate bead formation, precoating with a polycation, multistep diffusion of drug into the bead and final coating with a polycation. Even using this complex procedure, a maximal loading of only 30 wt % could be achieved. The disclosures of these and other publications referred to throughout this application are incorporated herein by reference. BRIEF SUMMARY OF THE INVENTION We have now discovered that if we prepare porous particles of a composition (such as calcium alginate microspheres) by dispersing a solution of a polymeric anionic material (such as sodium alginate or other polysaccharides bearing carboxyl functionalities) into a solution of a polycation (such as calcium chloride solution) and then dehydrate the particles by controlled dehydration (e.g. lyophilization), a highly porous bioerodible particle forms into which therapeutic agents can be diffused from an external solution. Once the diffusion process has been completed, the particles may again be dehydrated by controlled dehydration, and then coated with a polycatio. We have further discovered, that the amount of polycation used to coat the particles can control the release of an incorporated active ingredient within unexpectedly wide limits. In this way, crosslinked, polycation coated particles having a drug loading in excess of 50 wt % and that can release drugs in a controlled manner have been achieved. It is an objective of this invention to provide porous bioerodible compositions for the sequestration and sustained delivery of active ingredients, which compositions are well tolerated by mammals and enable the sequestration and delivery of a greater amount of the active ingredient than prior art compositions. Accordingly, the invention provides macroporous compositions of ionically cross-linked polyanions and polycations into which more than 50 wt % of a water-soluble active agent can be incorporated and from which it can be released in a controlled manner. Active agents can be introduced subsequently by diffusing the active agent into the porous compositions from an external aqueous solution. Because the active agent is never exposed to harsh experimental conditions or to organic solvents, biological activity is retained. A preferred embodiment comprises macroporous bioerodible particles prepared from alginate and chitosan, which have been ionically crosslinked and thus have not undergone any changes that would alter their GRAS status. Although a number of experimental procedures can be utilized to prepare the compositions of the invention, a particularly advantageous method uses calcium alginate particles having a preselected size and size distribution which have been created by spraying sodium alginate into a calcium chloride solution and then lyophilizing to create a porous structure, stirring in a drug solution and then incubating in a chitosan solution. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A is a scanning electron micrograph (SEM) of the surfaces of alginate/chitosan microspheres (particles according to this invention); FIG. 1B is a SEM of the interiors. FIG. 2 illustrates the size ditribution of alginate/chitosan microspheres. FIG. 3 illustrates the release of bovine serum albumin (BSA) sequestered within alginate/chitosan microspheres. FIG. 4 illustrates the release of IL-2 sequestered within alginate/chitosan microspheres. FIG. 5 illustrates the sustained release of ricin toxoid vaccine sequestered within alginate/chitosan microspheres. FIG. 6 illustrates the immunogenicity of ricin toxoid vaccine sequestered within alginate/chitosan microspheres. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In the instant invention, a porous delivery vehicle comprised of a polymeric composition having an active ingredient held within the pores is utilized to provide a controlled time release of the active ingredient. In accordance with the present invention, the active ingredient is released from the porous delivery vehicle in a sustained fashion. One property of the compositions provided herein that distinguish them from all prior art is their greatly enhanced ability to absorb drugs and the prolonged release possible. The prior art neither teaches nor suggests macroporous polyelectrolyte compositions of the type disclosed herein prepared by controlled dehydration, nor discloses prolonged release or readily controllable kinetics. DEFINITIONS "Porous matrix" denotes the physical structure of the composition formed as a result of the electrostatic ionic interaction between a first polymeric ion with a multifunctional cation and a third multivalent or polymeric ion having an opposite charge. When such a first and second and third polymeric or polyvalent ions having opposite charges are contacted in a solution, they often form spherical polyelectrolyte particles, termed microspheres or beads, which may range in size from less than 1 to about 1000 .mu.m. However, other shapes, such as irregularly shaped particles, or larger compositions readily visible to the naked eye, are also contemplated. "Bioerodible" signifies that the porous matrix may be disassembled or digested into its component molecules by the action of the environment or particularly by the action by living organisms, and optionally metabolized or digested into simpler constituents without poisoning or distressing the environment or the organism. Bioerodible compositions according to the invention are preferably made of GRAS materials. Preferred polyelectrolyte combinations are alginate/chitosan, alginate/polylysine, alginate/polyarginine, gum arabic/albumen, galactan sulfate/chitosan, alginate/polyvalent cations (e.g., calcium), polyphosphagine/polyvalent cations, but other materials and combinations are possible that are within the knowledge of persons of ordinary skill. The concentration of the polymeric anionic molecule and the polymeric cationic molecule used to formulate the composition independently ranges from about 0.1 to about 15% w/v. Preferably, the concentration of the polymeric anionic molecule and the polymeric cationic molecule used to formulate the composition independently ranges from about 0.5 to about 5% w/v. Most preferably, the concentration of the polymeric anionic molecule and the polymeric cationic molecule used to formulate the composition independently ranges from about 0.5 to about 3% w/v. Different proportions of polycations and polyanions may be used, depending on the nature of the active ingredient, the desired pore size, the desired capacity to uptake water and/or the desired rate of releasing the active ingredient. "Alginate" or "algin" denotes the sodium salt of alginic acid (polymannuronic acid). Alginate is a gelling polysaccharide, typically extracted from kelp; and is the sodium salt of a linear polymer of .beta.-(1.fwdarw.4)-D-mannosyluronic acid and .alpha.-(1.fwdarw.4)-D-gulosyluronic acid residues, the proportions of which vary with the source and state of maturation of the plant. "Chitosan" is the deacylated form of chitin, and is a cellulose-like biopolymer consisting predominantly of unbranched chains of .beta.-(1.fwdarw.4)-2-amino-2-deoxy-D-glucose (also known as D-glucosamine) residues. "Macroporous" denotes a composition comprised of a network of interconnected pores whose capacity to absorb and retain drugs has been enhanced in comparison with composition lacking a network of interconnected pores. A preferred method for forming such a network of interconnected pores is by controlled dehydratation. "Controlled dehydration" denotes methods for dehydration which avoid collapsing the porous network and/or maintain or enhance the macroporous matrix and fluid uptake. The preferred method of controlled dehydration for the compositions of this invention is lyophilization, also known as freeze drying, but other methods may be used, such as exposure to a graded series of solvents (e.g., alcohols) that extract the water without collapsing the structure of the polyelectrolyte matrix. "Sequestration" denotes that an active ingredient is reversibly confined or held within the porous spaces of the porous matrix. The active ingredient may be a freely diffusible solute in a fluid medium that fills the pore, but the term sequestration also encompasses active ingredients in the solid or gaseous state, or an interaction between the matrix and the active ingredient, such as an electrostatic attraction or a hydrophobic interaction, that reversibly attaches the active ingredient to the matrix. An "active ingredient" is any functional ingredient or ingredient which is released from the porous matrix to perform some function. "Active ingredient" is broadly defined to encompass any functional ingredient so long as it is held within the network of pores of a porous composition according to the present invention. Thus, for example, the active ingredient might comprise anti-infectives (such as antibiotics, fungicides, scabicides, pediculicides or miscellaneous anti-infectives such as iodine), anti-inflammatory agents, antipruritics, astringents, anti-hidrotics, keratolytic agents and caustics, keratoplastic agents, rubefacients, sunscreens, pigmentation agents, emollients, demulcents, protectants and detergents. The active ingredient might be used in a variety of applications such as beauty aids, including cosmetic and toiletry applications, and the active ingredient may be incorporated in a medium such as a gel, a cream, a lotion, an ointment, a liquid or the like. The active ingredient may be a living cell, a vaccine, a growth factor, a protein or peptide drug (.e.g. insulin, erythropoietin), a vitamin (e.g., vitamin B-12). "Administered to a mammal" means that the composition containing an active ingredient is administered orally, parenterally, enterically, gastrically, topically, transdermally, subcutaneously, locally or systemically. The composition may optionally be administered together with a suitable pharmaceutical excipient, which may be a saline solution, ethyl cellulose, acetotephtalates, mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, glucose, sucrose, carbonate, and the like. "Sustained delivery" or "sustained time release" denotes that the active ingredient is released from the delivery vehicle at an ascertainable and manipulatable rate over a period of minutes, hours, days, weeks or months, ranging from about thirty minutes to about two months. The release rate may vary as a function of a multiplicity of factors such as particle size, particle composition, particle hydration, pore size, solvent composition, solubility of the active ingredient and molecular weight and charge density of the active ingredient. Sequestration of an active ingredient within the pores of a porous delivery vehicle may serve one or more purposes. It may limit the toxic effect of a compound, prolong the time of action of a compound in a controlled manner, permit the release of an active ingredient in a precisely defined location in an organism, protect unstable compounds against the action of the environment, convert a liquid or gaseous substance into a pseudosolid material, or mask an unpleasant odor or taste. To utilize a delivery vehicle in accordance with the method of the present invention, the delivery vehicle is mixed with a medium to form a mixture which is applied to a surface or administered to a mammal. The active ingredient is then released from the network of pores by diffusion or volatilization. Alternatively, the active ingredient may be released by a force such as pressure. Pressure release may by gradual and continuous. Pressure release may also be triggered by intermittent pressure which may vary the concentration of active ingredient released from the network of pores. The delivery vehicle may be incorporated in a medium, such as a solution, suspension, tablet, pill, capsule, powder, gel, cream, lotion, ointment, liquid, aerosol or the like, which may then be applied to a surface, injected, is inhaled, or administered to a mammal orally or parenterally. For example, the delivery vehicle containing the active ingredient might be incorporated into cosmetic preparations such as hand creams, acne products, deodorants, antiperspirants, baby powders, foot powders, body powders, lip ices, lip sticks, baby creams and lotions, mouthwashes, dentifrices, medicated facial creams and lotions, shampoos, shaving creams, pre- and after-shave lotions, depilatories and hairgrooming preparations. The active ingredient may then be released by pressure, diffusion or volatilization. Thus, the delivery vehicle is uniquely suited for use in a wide variety of applications in which it is desirable to release an active ingredient by one or more methods. |
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