Details for Patent: 6,428,814

Title:	Bioadhesive nanoparticulate compositions having cationic surface stabilizers
Abstract:	Bioadhesive nanoparticulate compositions, comprising active agent particles and one or more cationic surface stabilizers, are described. The cationic surface stabilizers prevent aggregation of the nanoparticles and increase bioadhesion of the nanoparticles to biological substrates, such as an insect, teeth, bone, nails, chitin, feathers, scales, mucous, skin, hair, plant tissue, etc. The particles may consist of pharmacologically active compounds (e.g., drug compounds for human or veterinary use), agricultural chemicals (pesticides, herbicides, fertilizers, and the like), cosmetic agents, consumer products (coloring agents, flavors, or fragrances), or other materials which function by interacting with biological substrates. In addition, the invention relates to methods of preparing and using such bioadhesive nanoparticulate compositions.
Inventor(s):	Bosch; H. William (King of Prussia, PA), Cooper; Eugene R. (King of Prussia, PA), McGurk; Simon L. (King of Prussia, PA)
Assignee:	Elan Pharma International Ltd. (Shannon County Clare, IL)
Filing Date:	Oct 08, 1999
Application Number:	09/414,159
Claims:	1. A stable bioadhesive nanoparticulate composition comprising: (a) active agent particles in a semi-crystalline state, an amorphous state, a mixture of crystalline and semi-crystalline, a mixture of crystalline and amorphous, or a mixture of crystalline, semi-crystalline, and amorphous; and (b) adsorbed to the surface thereof at least one cationic surface stabilizer, wherein the active agent particles have an effective average particle size of less than about 4000 nm, wherein the nanoparticulate composition adsorbs to a biological surface, and wherein the nanoparticulate composition does not contain solvent residues resulting from solvent extraction or solvent precipitation. 2. The composition of claim 1, wherein the active agent is selected from the group consisting of a poorly water-soluble active agent and a water-soluble active agent. 3. The composition of claim 1, wherein the active agent is selected from the group consisting of a drug, vitamin, herb, cosmetic agent, coloring agent, flavor agent, fragrance agent, sunscreen, moisturizer, deodorant, food product, hair conditioner agent, hair dye, hair spray agent, hair cosmetic agent, hair cleanser agent, depilatory agent, insecticide, fertilizer, pesticide, herbicide, germicide, and plant growth regulating agent. 4. The composition of claim 3, wherein the drug is selected from the group consisting of proteins, peptides, nutriceuticals, anti-obesity agents, corticosteroids, elastase inhibitors, analgesics, anti-fungals, oncology therapies, anti-emetics, analgesics, cardiovascular agents, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agents, antiepileptics, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives, astringents, beta-adrenoceptor blocking agents, blood products and substitutes, cardiac inotropic agents, contrast media, cough suppressants, diagnostic agents, diagnostic imaging agents, diuretics, dopaminergics, haemostatics, immunological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin and biphosphonates, prostaglandins, radio-pharmaceuticals, sex hormones, anti-allergic agents, stimulants and anoretics, sympathomimetics, thyroid agents, vasodilators, xanthines, acne medication, alpha-hydroxy formulations, cystic-fibrosis therapies, asthma therapies, emphysema therapies, respiratory distress syndrome therapies, chronic bronchitis therapies, chronic obstructive pulmonary disease therapies, organ-transplant rejection therapies, therapies for tuberculosis and other infections of the lung, and respiratory illness therapies associated with acquired immune deficiency syndrome. 5. The composition of claim 1, wherein the composition is formulated for administration selected from the group consisting of vaginal, ocular, nasal, buccal, oral, colonic, topical, and subcutaneous administration. 6. The composition of claim 1, wherein the at least one cationic surface stabilizer is selected from the group consisting of a polymer, a biopolymer, a polysaccharide, a cellulosic, an alginate, a nonpolymeric compound, and a phospholipid. 7. The composition of claim 1, wherein the surface stabilizer is selected from the group consisting of benzalkonium chloride, polymethylmethacrylate trimethylammonium bromide, polyvinylpyrrolidone-2-dimethylaminoethyl methacrylate dimethyl sulfate, and hexadecyltrimethyl ammonium bromide. 8. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 3500 nm. 9. The composition of claim 1, wherein the composition further comprises one or more pharmaceutically acceptable excipients. 10. A stable bioadhesive nanoparticulate composition comprising: (a) active agent particles in a semi-crystalline state, an amorphous state, a mixture of crystalline and semi-crystalline, a mixture of crystalline and amorphous, or a mixture of crystalline, semi-crystalline, and amorphous, wherein the active agent particles are present in an amount of about 99.99 to 0.01(w/w) based on the total weight of the composition; and (b) adsorbed to the surface thereof at least one cationic surface stabilizer, wherein the active agent particles have an effective average particle size of less than about 4000 nm, and wherein the nanoparticulate composition adsorbs to a biological surface. 11. A stable bioadhesive nanoparticulate composition comprising: (a) active agent particles in a semi-crystalline state, an amorphous state, a mixture of crystalline and semi-crystalline, a mixture of crystalline and amorphous, or a mixture of crystalline, semi-crystalline, and amorphous; and (b) adsorbed to the surface thereof at least one cationic surface stabilizer, wherein the surface stabilizer is present in an amount of about 0.001 to about 99.999% (w/w) based on the total weight of the composition, wherein the active agent particles have an effective average particle size of less than about 4000 nm, and wherein the nanoparticulate composition adsorbs to a biological surface. 12. The composition of claim 1, wherein the composition adsorbs to a biological surface selected from the group consisting of an insect, teeth, bone, nails, chitin, feathers, scales, mucous, skin, hair, and plant tissue. 13. The composition of claim 1 in a dry powder form. 14. The composition of claim 1, wherein the effective average particle size of the agent particles less than about 3000 nm. 15. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 2500 nm. 16. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 2000 nm. 17. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 1500 nm. 18. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 1000 nm. 19. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 800 nm. 20. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 700 nm. 21. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 600 nm. 22. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 400 nm. 23. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 300 nm. 24. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 250 nm. 25. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 200 nm. 26. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 100 nm. 27. The composition of claim 1, wherein the effective average particle size of the agent particles is less than about 50 nm.