Absorption of therapeutic agents across mucosal membranes or the skin

Abstract

Absorption of a therapeutic agent across a mucosal membrane or the skin can be enhanced using an absorption enhancer comprising a hydroxy fatty acid ester of polyethylene glycol.

1 . A method of administering a therapeutic agent via a mucosal membrane comprising:
 applying to a mucosal membrane a pharmaceutical composition comprising a therapeutic agent and an absorption enhancer comprising polyethylene glycol 660 hydroxy fatty acid, wherein the therapeutic agent has a log P value less than about 1 and:   
       (a) is a peptide, protein, nucleic acid, antigen or vaccine; or 
       (b) is not a substrate for P-glycoprotein (P-Gp). 
     
     
         2 . The method according to  claim 1 , wherein the pharmaceutical composition is in the form of a spray, aerosol, dry powder, oral tablet or capsule, buccal or sublingual tablet, pastille or lozenge, pessary, suppository, enema, drops, or a thin film. 
     
     
         3 . The method according to  claim 1 , wherein the mucosal membrane is the nasal, buccal, pulmonary, vaginal or rectal mucosa. 
     
     
         4 . The method according to  claim 3 , wherein the pharmaceutical composition is in a form suitable for administration to the mucosal membranes of the nasal cavity and/or respiratory tract. 
     
     
         5 . The method according to  claim 3 , wherein the pharmaceutical composition is in the form of a solution, gel, powder or nasal insert. 
     
     
         6 . The method according to  claim 3 , wherein the pharmaceutical composition is in the form of an aqueous solution or a dry powder. 
     
     
         7 . The method according to  claim 1 , wherein the pharmaceutical composition is in the form of spray-dried or freeze-dried particles, microspheres or nanoparticles. 
     
     
         8 . The method according to  claim 1 , wherein the pharmaceutical composition further comprises a bioadhesive agent, gelling agent and/or thickening agent. 
     
     
         9 . The method according to  claim 1 , wherein the pharmaceutical composition further comprises one or more additional absorption enhancers. 
     
     
         10 . The method according to  claim 9 , wherein the additional absorption enhancer is selected from the group consisting of cyclodextrin, bile salts, poly-L-arginine, chitosan, phospholipids, lysophospholipids, polyacrylic acid, hyaluronic acids, sodium caprate and aminated gelatin. 
     
     
         11 . The method according to  claim 1 , wherein an amount of absorption enhancer present in the composition is at least 0.1% by weight of the total composition. 
     
     
         12 . The method according to  claim 11 , wherein an amount of absorption enhancer present in the composition is at most 40% by weight of the total composition. 
     
     
         13 . The method according to  claim 12 , wherein an amount of absorption enhancer present in the composition is 5 to 40% by weight of the total composition. 
     
     
         14 . The method according to  claim 1 , wherein the therapeutic agent is selected from the group consisting of insulin, glucagons, leuprolide, growth hormone, Parathyroid hormone, calcitonin, vascular endothelium growth factor, Erythropoietin, heparin, oxytocin, tyrosine, enkephalin, tyrotropin releasing hormone, follicle stimulating hormone, leuteinising hormone, vasopressin, and vasopressin analogs, catalase, superoxide dismutase, interleukin-II, interferons, colony stimulating factor, tumour necrosis factor, melanocyte stimulating hormone, glucagon-like peptide-1 and derivatives thereof, glucagon-like peptide-2 and derivatives thereof, katacalcin, cholecystekinin-12, cholecystekinin-8, exendin, gonadoliberin-related peptide, insulin-like protein, leucine-enkephalin, methionine-enkephalin, leumorphin, neurophysin, copeptin, neuropeptide Y, neuropeptide AF, PACAP-related peptide, pancreatic hormone, peptide YY, urotensin, intestinal peptide, adrenocorticotropic peptide, epidermal growth factor, prolactin, luteinising hormone releasing hormone (LHRH), LHRH agonists, growth hormone releasing factor, somatostatin, gastrin, tetragastrin, pentagastrin, endorphins and angiotensins, thyrotropin releasing hormone, tumour necrosis factor, granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor, macrophage-colony stimulating factor, heparinase, vascular endothelial growth factor, enzymes and glycoproteins. 
     
     
         15 . A method of administering a therapeutic agent via a mucosal membrane comprising:
 applying to a mucosal membrane of the nasal cavity and/or respiratory tract a pharmaceutical composition comprising a therapeutic agent and an absorption enhancer comprising polyethylene glycol 660 hydroxy fatty acid, wherein the therapeutic agent is growth hormone or parathyroid hormone, and the pharmaceutical composition is in the form of an aqueous solution or a dry powder.   
     
     
         16 . The method according to  claim 15 , wherein the pharmaceutical composition is in the form of an aqueous solution. 
     
     
         17 . The method according to  claim 15 , the pharmaceutical composition is in the form of a dry powder. 
     
     
         18 . The method according to  claim 17 , wherein the dry powder comprises spray-dried or freeze-dried particles, microspheres or nanoparticles. 
     
     
         19 . The method according to  claim 15 , wherein the pharmaceutical composition further comprises a bioadhesive agent, gelling agent and/or thickening agent. 
     
     
         20 . The method according to  claim 15 , wherein the pharmaceutical composition further comprises one or more additional absorption enhancers. 
     
     
         21 . The method according to  claim 20 , wherein the additional absorption enhancer is selected from the group consisting of cyclodextrin, bile salts, poly-L-arginine, chitosan, phospholipids, lysophospholipids, polyacrylic acid, hyaluronic acids, sodium caprate and aminated gelatin. 
     
     
         22 . The method according to  claim 15 , wherein an amount of absorption enhancer present in the composition is at least 0.1% by weight of the total composition. 
     
     
         23 . The method according to  claim 22 , wherein an amount of absorption enhancer present in the composition is at most 40% by weight of the total composition. 
     
     
         24 . The method according to  claim 23 , wherein an amount of absorption enhancer present in the composition is 5 to 40% by weight of the total composition. 
     
     
         25 . The method according to  claim 15 , wherein the aqueous solution or dry powder is essentially free of liposomes, vesicles, micelles, or microemulsions.