Compositions for transdermal delivery of active agents

Abstract

Disclosed herein are compositions that are useful in effecting the transdermal delivery of therapeutic agents. More particularly, the disclosed transdermal compositions may include a fatty alcohol (for example, octanol), a terpene (for example, limonene), and an active agent comprising an amine moiety.

1 . A pharmaceutically acceptable transdermal composition comprising a fatty alcohol, a terpene, and an active agent. 
     
     
         2 . The pharmaceutically acceptable transdermal composition of  claim 1 , wherein the active agent has at least one primary, secondary or tertiary amine moiety. 
     
     
         3 . The pharmaceutically acceptable transdermal composition of  claim 1 , wherein the active agent has a negatively charged carbonyl moiety. 
     
     
         4 . (canceled) 
     
     
         5 . The pharmaceutically acceptable transdermal composition of  claim 4 , wherein the active agent is selected from the group consisting of carbidopa, levodopa, and a pharmaceutically acceptable salt thereof. 
     
     
         6 . The pharmaceutically acceptable transdermal composition of  claim 1 , wherein the active agent is selected from the group consisting of opipramol, physostigmine, chlorpheniramine, lidocaine, metoprolol, nicotine, salbutmol, timolol, diltiazem, quinidine, imipramine, quetiapine, venlafaxine, and a pharmaceutically acceptable salt thereof. 
     
     
         7 . The pharmaceutically acceptable transdermal composition of  claim 1 , wherein (i) the composition has about 1 to about 10 weight percent active agent; and/or (ii) the composition has about 1 to about 5 weight percent fatty alcohol; and/or (iii) the fatty alcohol is octanol, preferably 1-octanol. 
     
     
         8 . The pharmaceutically acceptable transdermal composition of  claim 1 , wherein the composition is about 0.25 to about 5 weight percent terpene. 
     
     
         9 . The pharmaceutically acceptable transdermal composition of  claim 1 , wherein the terpene is d-limonene. 
     
     
         10 . The pharmaceutically acceptable transdermal composition of  claim 1 , further comprising a fatty acid ester. 
     
     
         11 . The pharmaceutically acceptable transdermal composition of  claim 10 , wherein the fatty acid ester is lauroglycol. 
     
     
         12 . The pharmaceutically acceptable transdermal composition of  claim 11 , wherein the weight ratio of fatty alcohol to lauroglycol is about 3:1 to about 1.5:1. 
     
     
         13 . The pharmaceutically acceptable transdermal composition of  claim 10 , wherein the composition is about 0.1 to about 5.0 weight percent fatty acid ester. 
     
     
         14 . The pharmaceutically acceptable transdermal composition of  claim 1 , further comprising hydroxypropyl methyl cellulose. 
     
     
         15 . The pharmaceutically acceptable transdermal composition of  claim 1 , further comprising an organic acid, wherein the organic acid is selected from the group consisting of ascorbic acid, tartaric acid, malic acid, succinic acid, fumaric acid, citric acid, lactic acid, glutamic acid, or aspartic acid, more preferably glutamic acid, aspartic acid, and tartaric acid. 
     
     
         16 . The pharmaceutically acceptable transdermal composition of  claim 1 , further comprising a basic amino acid, wherein the basic amino acid is selected from the group consisting of arginine, lysine and histidine. 
     
     
         17 . The pharmaceutically acceptable transdermal composition of  claim 1 , further comprising propylene glycol. 
     
     
         18 . A pharmaceutically acceptable transdermal composition comprising octanol, limonene, organic acid, and an active agent comprising an amine moiety. 
     
     
         19 . The pharmaceutically acceptable transdermal composition of  claim 18 , wherein the active agent is selected from the group consisting of opipramol and a pharmaceutically acceptable salt thereof. 
     
     
         20 - 24 . (canceled) 
     
     
         25 . The pharmaceutically acceptable transdermal composition of  claim 18 , wherein (i) the composition has about 0.5 to about 7.5 weight percent octanol; and/or (ii) the composition has about 0.25 to about 5 weight percent limonene. 
     
     
         26 . The pharmaceutically acceptable transdermal composition of  claim 18 , further comprising lauroglycol. 
     
     
         27 . The pharmaceutically acceptable transdermal composition of  claim 26 , wherein the weight ratio of octanol to lauroglycol is about 3:1 to about 1.5:1. 
     
     
         28 . The pharmaceutically acceptable transdermal composition of  claim 18 , further comprising arginine. 
     
     
         29 . The pharmaceutically acceptable transdermal composition of  claim 18 , wherein the transdermal composition, when transdermally administered to a patient, delivers more than twice the amount of active agent to said patient over 20 hours as compared to (i) a formulation that does not include octanol; (ii) a formulation that does not include limonene; or (iii) a formulation that does not include an organic acid. 
     
     
         30 - 32 . (canceled) 
     
     
         33 . The pharmaceutically acceptable composition of  claim 1 , wherein the active agent is selected from the group consisting of atorvastatin, amoxicillin, fexofenadine, pravastatin, cefalexin, furosemide, ibuprofen, naproxen, gemfibrozil, mupirocin, cefprozil, methotrexate, tretinoin, cefuroxime, etodalac, penicillin, folic acid, fosinopril, ursodiol, indometacin, falsartan, lisinopril, diclofenac (Na salt), fluvoxamine, memantine, amlodipine, cefdinir, lamotrigine, amphetamine, triamterene, minocycline, phentermine, famciclovir, trimethoprim, aciclovir, hydralazine, doxazosin, dextro-amphetamine, famotidine, desipramine, atomoxetine, azathioprine, bromocriptine, burpropione, clonidine, dexmethyl-phenidate, duloxetine, enalapril, Formoterol, Hydrochloro-thiazide, Lornoxicam, Metoprolol, Sertraline Paroxetine, Fluoxetine, Ramipril, Salbutamol, Bupropion, Carvedilol, Atenolol, Nifedipine, Felodipine, Enalapril, Quinapril, Tizanidine, Clonidine, Benzonatate, Propranolol HCl, Benazepril, Paroxetine, Allopurinol, Labetalol HCl, Sotalol, Torasemide, Bisoprolol, Pindolol, and Pseudo-ephedrine, Miconazole, Econazole, Clotrimazole, Ketoconazole, Quinidine, Pargiline, Alprazolam, Apomorphine, Bromazepam, Burenorphine, Chlorpheniramine, Diltiazem, Dipyridamole, Domperidone, Galantamine (HBr), Haloperidol, Hydromorphone, Levomepromazine, Methadone, Methazolamide, Metformin HCl, Azithromycin, Omeprazol, Fentanyl, Oxycodone, Risperidone, Tramadol, Citalopram, Ondansetro, Morphine, Dextropropoxyphene, Cyclobenzaprine HCl, Ciprofloxacin, Ranitidine, Verapamil, Baclofen, Oxybutynin, Venlafaxine HCl, Opipramol, Lidocaine, Oxcarbazepine, Carisoprodol, Meloxicam, glibenclamide (glyburide), phenytoin, glimepiride, barbital, metho-carbamol, modafinil, methysergide, lisinopril, levosalbutamol, formotoerol, arformoterol, ipratorium bromide, voriconazole, ciclopirox, and entacapone.