Patent Application

App. No. 12/757,005

Abstract

Claims (24)

1 . A composition comprising:

a semipermeable coating;

particles of a medicament having an effective average particle size of less than or about 2 μm and a surface stabilizer adsorbed on the surface of the medicament particles; and

a solubilizing agent.

2 . The composition of claim 1 , wherein the semipermeable coating is selected from the group consisting of a controlled-porosity microporous coating, a water swellable coating, and mixtures and combinations thereof.

3 . The composition of claim 1 , wherein the semipermeable coating is a controlled-porosity microporous coating comprising a polymer that is insoluble in an environment of use and a pore forming additive that is soluble in the environment of use.

4 . The composition of claim 3 , wherein the polymer is selected from the group consisting of cellulosic polymers, methacrylates and phthalates, and

wherein the pore forming additive is selected from the group consisting of HPMC, PVP, polyhydric alcohols, and sugars.

5 . The composition of claim 3 , wherein the percent by weight of pore forming additive in the controlled-porosity microporous coating is selected from the group consisting of 0.5%. 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 13%, 15%, 17%, 19%, 21%, 22%, 24%, 26%, 28%,) 30%, 32%, 34%, 36%, 38%, 41%, 43%, 45%, 47%, 49%, and 50%.

6 . The composition of claim 1 , wherein the medicament is selected from a class of medicaments selected from the group consisting of abortifacients, ACE inhibitors, α- and β-adrenergic agonists, α- and β-adrenergic blockers, adrenocortical suppressants, adrenocorticotropic hormones, alcohol deterrents, aldose reductase inhibitors, aldosterone antagonists, anabolics, analgesics (including narcotic and non-narcotic analgesics), androgens, angiotensin II receptor antagonists, anorexics, antacids, anthelminthics, antiacne agents, antiallergics, antialopecia agents, antiamebics, antiandrogens, antianginal agents, antiarrhythmics, antiarteriosclerotics, antiarthritic/antirheumatic agents, antiasthmatics, antibacterials, antibacterial adjuncts, anticholinergics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antidiarrheal agents, antidiuretics, antidotes to poison, antidyskinetics, antieczematics, antiemetics, antiestrogens, antifibrotics, antiflatulents, antifungals, antiglaucoma agents, ant igonadotropins, antigout agents, antihistaminics, antihyperactives, antihyperlipoproteinemics, antihyperphosphatemics, antihypertensives, antihyperthyroid agents, antihypotensives, antihypothyroid agents, anti-inflammatories, antimalarials, antimanics, antimethemoglobinemics, antimigraine agents, antimuscarinics, antimycobacterials, antineoplastic agents and adjuncts, antineutropenics, antiosteoporotics, antipagetics, antiparkinsonian agents, antipheochromocytoma agents, antipneumocystis agents, antiprostatic hypertrophy agents, antiprotozoals, antipruritics, antipsoriatics, antipsychotics, antipyretics, antirickettsials, antiseborrheics, antiseptics/disinfectants, antispasmodics, antisyphylitics, antithrombocythemics, antithrombotics, antitussives, antiulceratives, antiurolithics, antivenins, antiviral agents, anxiolytics, aromatase inhibitors, astringents, benzodiazepine antagonists, bone resorption inhibitors, bradycardic agents, bradykinin antagonists, bronchodilators, calcium channel blockers, calcium regulators, carbonic anhydrase inhibitors, cardiotonics, CCK antagonists, chelating agents, cholelitholytic agents, choleretics, cholinergics, cholinesterase inhibitors, cholinesterase reactivators, CNS stimulants, contraceptives, COX-I and COX II inhibitors, debriding agents, decongestants, depigmentors, dermatitis herpetiformis suppressants, digestive aids, diuretics, dopamine receptor agonists, dopamine receptor antagonists, ectoparasiticides, emetics, enkephalinase inhibitors, enzymes, enzyme cofactors, estrogens, expectorants, fibrinogen receptor antagonists, fluoride supplements, gastric and pancreatic secretion stimulants, gastric cytoprotectants, gastric proton pump inhibitors, gastric secretion inhibitors, gastroprokinetics, glucocorticoids, α-glucosidase inhibitors, gonad-stimulating principles, growth hormone inhibitors, growth hormone releasing factors, growth stimulants, hematinics, hematopoietics, hemolytics, hemostatics, heparin antagonists, hepatic enzyme inducers, hepatoprotectants, histamine H2 receptor antagonists, HIV protease inhibitors, HMG CoA reductase inhibitors, immunomodulators, immunosuppressants, insulin sensitizers, ion exchange resins, keratolytics, lactation stimulating hormones, laxatives/cathartics, leukotriene antagonists, LH-RH agonists, lipotropics, 5-lipoxygenase inhibitors, lupus erythematosus suppressants, matrix metalloproteinase inhibitors, mineralocorticoids, miotics, monoamine oxidase inhibitors, mucolytics, muscle relaxants, mydriatics, narcotic antagonists, neuroprotectives, nootropics, NSAIDS, ovarian hormones, oxytocics, pepsin inhibitors, pigmentation agents, plasma volume expanders, potassium channel activators/openers, progestogens, prolactin inhibitors, prostaglandins, protease inhibitors, radio-pharmaceuticals, 5α-reductase inhibitors, respiratory stimulants, reverse transcriptase inhibitors, sedatives/hypnotics, serenics, serotonin noradrenaline reuptake inhibitors, serotonin receptor agonists, serotonin receptor antagonists, serotonin uptake inhibitors, somatostatin analogs, thrombolytics, thromboxane A 2 receptor antagonists, thyroid hormones, thyrotropic hormones, tocolytics, topoisomerase I and II inhibitors, uricosurics, vasomodulators including vasodilators and vasoconstrictors, vasoprotectants, xanthine oxidase inhibitors.

7 . The composition of claim 1 , wherein the medicament is poorly soluble in an environment of use.

8 . The composition of claim 1 , wherein the effective average particle size is selected from the group consisting of less than or about 1900 nm, 1800 nm, 1700 nm, 1600 nm, 1500 nm, 1400 nm, 1300 nm, 1200 nm, 1100 nm, 1000 nm (1 μm), 900 nm, 800 nm, 700 nm, 600 nm, 500 nm, 400 nm, 300 nm, 200 nm, 150 nm, 100 nm, 75 nm, and 50 nm.

9 . The composition of claim 1 , wherein the particles of the medicament have a D 90 selected from the group consisting of less than or about 5000 nm, 4900 nm, 4800 nm, 4700 nm, 4600 nm, 4500 nm, 4400 nm, 4300 nm, 4200 nm, 4100 nm, 3000 nm, 3900 nm, 3800 nm, 3700 nm, 3600 nm, 3500 nm, 3400 nm, 3300 nm, 3200 nm, 3100 nm, 3000 nm 2900 nm, 2800 nm, 2700 nm, 2600 nm, 2500 nm, 2400 nm, 2300 nm, 2200 nm, 2150 nm, 2100 nm, 2075 nm, and 2000 nm.

10 . The composition of claim 1 , wherein the surface stabilizer is selected from the group consisting of hydroxypropyl methylcellulose (HPMC), dioctyl sodium sulfosuccinate (DOSS), sodium lauryl sulfate (SLS), hydroxypropyl cellulose, polyvinylpyrrolidone, sodium deoxycholate, block copolymers based on ethylene oxide and propylene oxide, copolymers of vinylpyrrolidone and vinyl acetate, lecithin, polyoxyethylene sorbitan fatty acid esters, albumin, lysozyme, gelatin, macrogol 15 hydroxystearate, tyloxapol, and polyethoxylated castor oil.

11 . The composition of claim 1 , wherein the solubilizing agent is of a type and present in an amount sufficient to dissolve the medicament particles within the composition prior to delivery of the medicament to an environment of use.

12 . The composition of claim 11 , wherein the solubilizing agent is a surface-active agent or a pH-modulating agent.

13 . The composition of claim 11 , wherein the surface-active agent is selected from the group consisting of anionic, cationic, zwitterionic and nonionic surface-active agents.

14 . The composition of claim 12 , wherein the solubilizing agent is a pH-modulating agent and, when exposed to fluid of the environment of use, modifies the pH environment within the composition to favor an ionized form of the medicament.

15 . The composition of claim 12 , wherein the solubilizing agent is a pH-modulating agent selected from a weak acid or a weak base.

16 . The composition of claim 15 , wherein the weak acid is selected from the group consisting of adipic acid, ascorbic acid, citric acid, fumaric acid, gallic acid, glutaric acid, lactic acid, malic acid, maleic acid, succinic acid, tartaric acid and mixtures and combinations thereof.

17 . The composition of claim 15 , wherein the weak base is selected from the group consisting of arginine, lysine, tromethamine (TRIS), meglumine, diethanolamine, triethanolamine, conjugate bases of pharmaceutically acceptable weak acids, and mixtures and combinations thereof.

18 . The composition of claim 17 , wherein the conjugate bases of pharmaceutically acceptable weak acids are selected from the group consisting of sodium carbonate, sodium phosphate, calcium phosphate, trisodium citrate, and sodium ascorbate and mixtures or combinations thereof.

19 . The composition of claim 1 , wherein the drug delivery composition delivers to an environment of use a solution of medicament at a concentration that is higher than that defined by the native solubility of the medicament in the environment of use.

20 . The composition of claim 19 , wherein the concentration of is 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 210%, 220%, 230%, 240%, 250%, 260%, 270%, 280%, 290%, 300, 310%, 320%, 330%, 340%, 350%, 360%, 370%, 380%, 390%, 400%, 410%, 420%, 430%, 440%, 450%, 460%, 470%, 480%, 490%, 500%, 510%, 520%, 530%, 540%, 550%, 560%, 570%, 580%, 590%, 600%, 700%, 800% or 1000% higher than that defined by the native solubility of the medicament in the environment of use.

Assignments (14)