Claims for Patent: 8,257,744

Summary for Patent: 8,257,744

Title:	Pharmaceutical forms for the release of active compounds
Abstract:	Pharmaceutical form containing at least an active compound and a polymeric matrix, wherein said polymeric matrix comprises at least one polymer of cationic nature and at least one biodegradable polymer, process for the preparation thereof, pharmaceutical formulations comprising said pharmaceutical form, and their uses. The pharmaceutical form provides enhanced absorption of active compounds across the mucosa.
Inventor(s):	Lopez-Belmonte Encina; Ivan (Madrid, ES), Gutierro Aduriz; Ibon (Granada, ES), Maincent; Philippe (Nancy, FR)
Assignee:	Laboratorios Farmaceuticos Rovi, S.A. (Madrid, ES)
Application Number:	12/779,556
Patent Claims:	1. A pharmaceutical form, which is a granule or pellet, having an average particle diameter in the range of 0.1 to 1.2 mm and comprising at least one active compound and a polymeric matrix, wherein: a) the active compound is selected from the group consisting of: antibiotics, anti-inflammatory agents, anti-infectious agents, antiparasitic agents, hormones, substances with immunological activity, vaccines, immunomodulators, immunosuppressants, cytostatic agents, diuretics, agents with activity in the digestive system, agents with activity in the circulatory system, agents with activity in the respiratory system, human growth hormone, recombinant growth hormone, bovine growth hormone, growth-hormone releasing hormone, interferons, analgesics, agents with activity in the central nervous system, erythropoietin, somatostatin, gonadotropin-releasing hormone, follicle-stimulating hormone, oxytocin, vasopressin, parathyroid hormone, adrenocorticotropin, gonadotropin-releasing hormone, thrombopoietin, calcitonin, interferons, interleukins, insulins, unfractionated heparin, low molecular weight heparin, ultra-low molecular weight heparins, heparinoids, dermatan, glucosamines, chondroitins, auricular natriuretic factor, monoclonal antibodies, protease inhibitors, filgrastim, prostaglandins (PGE2 and PGI2), cyclosporin, cromolyn sodium, cromoglycate and its salts, vasopressin, vancomycin, neomycin, desferrioxamine, antimicrobial agents, antifungals, cytostatics, immunomodulators, vitamins, antivirals, antigens, ribonucleic acid, deoxyribonucleic acid, oligonucleotides, CPG sequences, plasmids, active compounds of protein nature, active compounds of polysaccharide nature, glucocerebrosidase, and derivatives and combinations thereof; b) the polymeric matrix comprises: i) at least one cationic polymer selected from the group consisting of cationic polymers and copolymers derived from acrylic and methacrylic acids with trimethylammonioethyl methacrylate, cholestyramine, chitosan and polylysine; and ii) at least one biodegradable polymer selected from the group consisting of polyesters, lactic acid polymers, copolymers of lactic acid and of glycolic acid, poly-c-caprolactone, polyanhydrides, poly(amides), poly(urethanes), poly(carbonates), poly(acetals), poly(ortho-esters), polymers and copolymers derived from acrylic acid, polyethylene oxides, polypropylene oxides, polyethylene and polypropylene oxide copolymers, polycyanacrylates, polydioxanones, poly (.alpha.-hydroxy acids), poly (.beta.-hydroxy acids), and polyphosphazenes; c) less than 20% wt, of the active compound is distributed on the surface of the pharmaceutical form; d) at least 80% wt, of the active compound is embedded within or surrounded by the polymeric matrix of the pharmaceutical form; e) the pharmaceutical form provides a release of at least 50% of active compound that is available for immediate release within 2 hours or less after the pharmaceutical form is exposed to an aqueous environment; f) the biodegradable polymer and the polycationic polymer are present in equivalent amounts; and g) the biodegradable polymer and the polycationic polymer are non-enteric. 2. The pharmaceutical form of claim 1, wherein the at least one biodegradable polymer comprises at least one neutral polymer or at least one anionic polymer. 3. The pharmaceutical form of claim 1, wherein it releases at least 60% of its charge of active compound available for immediate release in less than or about 3 hours. 4. The pharmaceutical form of claim 2, wherein the polymeric matrix comprises 10-90% by weight of anionic or neutral polymer and 10-90% of cationic polymer. 5. The pharmaceutical form of claim 4, wherein the cationic polymer is a polymer derived from methacrylic acid with quaternary ammonium groups, and the biodegradable polymer is a polyethylene and polypropylene oxide copolymer, PLGA, or polycaprolactone. 6. The pharmaceutical form of claim 1, wherein the pharmaceutical form is adapted for oral, peroral, sublingual, intraduodenal, intrajejunal, intraileal, intracolonic, rectal, intravaginal, nasal, intrapulmonary, ocular and/or otic administration. 7. The pharmaceutical form of claim 1, wherein the active compound is selected from the group consisting of enoxaparin, tinzaparin, bemiparin, fondaparinux and insulin. 8. The pharmaceutical form of claim 1, wherein the active compound is present in an amount of at least about 5% by weight of the pharmaceutical form. 9. The pharmaceutical form of claim 1, wherein at least 20% of the active compound that is available for immediate release from the pharmaceutical form is absorbed via the mucosa of the subject following administration of the pharmaceutical and formed to the subject. 10. The pharmaceutical form of claim 1, wherein less than 95% of the active compound present in the pharmaceutical form is degraded in the gastric region following oral administration of the pharmaceutical form to a subject. 11. A pharmaceutical formulation comprising a pharmaceutical form according to claim 1. 12. The pharmaceutical form according to claim 2, wherein at least one polymer of anionic or neutral nature and at least one polymer of cationic nature are present in a proportion of at least 10% each in relation to the weight of the polymeric matrix. 13. The pharmaceutical form according to claim 2, wherein the polymeric matrix comprises poly-.epsilon.-caprolactone as a polymer of anionic or neutral nature and a polymer derived from methacrylic acid with quaternary ammonium groups as a polymer of cationic nature, and the polymer derived from methacrylic acid with quaternary ammonium groups is a trimethylammonioethyl methacrylate chloride copolymer. 14. The pharmaceutical form according to claim 1, wherein the granule comprises a core and the polymeric matrix, wherein said core comprises the at least one active compound. 15. The pharmaceutical form according to claim 14, wherein the polymeric matrix forms part of the core. 16. The pharmaceutical form according to claim 14, wherein the polymeric matrix forms a coating layer on or over the core. 17. The pharmaceutical form according to claim 1 characterized in that it is a pellet manufactured by a granulation process which comprises the step of subjecting a composition comprising at least one active compound to a granulation process to produce a core. 18. The pharmaceutical form according to claim 17, wherein the manufacture process further comprises the step of coating the core with a composition comprising the at least one cationic polymer. 19. The pharmaceutical formulation according to claim 11, characterized in that it is an oral formulation. 20. The pharmaceutical formulation according to claim 11, wherein said formulation is a non-extended release formulation. 21. The pharmaceutical formulation according to claim 20, characterized in that it is an oral formulation.

Details for Patent 8,257,744

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2020-07-07
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2020-07-07
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2020-07-07