Transdermal delivery system

Abstract

A transdermal delivery system comprising a composition comprising a physiologically active agent and a penetration enhancer wherein the penetration enhancer comprises a combination of (i) an ester of salicylic acid, preferably selected from the C 6 to C 30 aliphatic ester of salicylic acid and (ii) polyethylene glycol (PEG) of average molecular weight no more than 300.

1 - 22 . (canceled) 
     
     
         23 . A transdermal delivery system comprising a composition comprising a physiologically active agent and a penetration enhancer wherein the penetration enhancer comprises a combination of (i) an ester of salicylic acid, and (ii) polyethylene glycol (PEG) of average molecular weight no more than 300. 
     
     
         24 . A transdermal delivery system according to  claim 23  wherein the ester of salicylic acid is a C 6  to C 12  alkyl ester. 
     
     
         25 . A transdermal delivery system according to  claim 23  wherein the ester of salicylic acid is ethylhexylester. 
     
     
         26 . A transdermal delivery system according to  claim 23  wherein the ester of salicylic acid is present in an amount of from 0.1 to 10% by weight of the total transdermal composition. 
     
     
         27 . A transdermal delivery system according to  claim 23  wherein the PEG of average molecular weight of no more than 300 is present in an amount in the range of from 0.1 to 40% by weight of the total composition. 
     
     
         28 . A transdermal delivery system according to  claim 23  wherein the weight ratio of ester of salicylic acid to polyethylene glycol of average molecular weight no more than 300 is in the range of from to 1:10 to 10:1. 
     
     
         29 . A transdermal delivery system according to  claim 23  wherein the composition comprises a solvent selected from C 2  to C 4  alkanol. 
     
     
         30 . A transdermal delivery system according to  claim 29  wherein the volatile solvent is preferably present in the composition in an amount in the range of from 70% to 95% by weight of the total composition. 
     
     
         31 . A transdermal delivery system according to  claim 23  wherein the composition consists essentially of:
 (i) the physiolocically active agent component which may include one or more physiologically active agents;   (ii) the penetration enhancer component consisting of a C 6  to C 12  alkyl ester of salicylic acid and a polyethylene glycol of average molecular weight no more than 300;   (iii) a volatile solvent consisting of one or more of ethanol and isopropanol; and   (iv) optionally a propellant.   
     
     
         32 . A transdermal delivery system according to  claim 23  wherein the total water content of the composition is less than 10% by weight of the total composition. 
     
     
         33 . A transdermal delivery system according to  claim 23  which is non-occlusive. 
     
     
         34 . A transdermal delivery system according to  claim 23  wherein the weight ratio of penetration enhancer to active is in the range of from 500:1 to 1:10. 
     
     
         35 . A transdermal delivery system according to  claim 23  wherein the physiologically active agent comprises one or more selected from the group consisting of antidepressants; women's health actives and hormones. 
     
     
         36 . A transdermal delivery system according to  claim 23  wherein the physiologically active agent comprises one or more of mirtazapine, metabolites, salts, enantiomers (including esmirtazapine), solvents, non-covalent complexes, chelates, hydrates, crystalline or amorphous forms thereof. 
     
     
         37 . A transdermal delivery system according to  claim 23  wherein the physiologically active agent comprises one or more hormones selected from the group consisting of: androgens, estrogens, selective estrogen receptor modulators, aromatase inhibitors, gonadotropins, progesterone, progestins, selective progesterone receptor modulators, antiprogestogen, antigonadotropins, GnRH:(receptor) agonists, antidiarrhoeals, cardiovascular system agents, antihypertensives, calcium channel blockers, proton pump inhibitors, antiarrhyrthmics, antiangina, beta-adrenergic blocking agents, cardiotonic glycosides, adrenergic stimulants, vasodilators, antimigraine preparations, anticoagulants, haemostatic agents, analgesics, antipyretics, hypnotics, antianxiety, neuroleptic and antipsychotic drugs, antidepressants, CNS stimulants such as caffeine, anti-alzheimer's agents, antiparkinson agents, lipid regulating drugs, anticonvulsants, antiemetics, antinauseants, non-steroidal antiinflammatory agents, antirheumatoid, muscle relaxants, agents used in gout and hyperuricaemia, diuretics, antidiuretics, obstetric drugs, prostaglandins, antimicrobials, antituberculosis drugs, antimalarials, antiviral agents, anthelmintics, cytotoxic agents, anorectics, agents used in hypercalcaemia, antitussives, expectorants, decongestants, bronchospasm relaxants, antihistamines, local anaesthetics, stratum corneum lipids, H2-receptor antagonists, neuromuscular blocking agents, smoking cessation agents, insecticides and other pesticides, dermatological agents, allergens, nutraceutically active compounds, keratolytics, psychicenergisers, anti-acne agents, anti-psoriasis agents, anti-itch agents, anticholinergic agents, and mixtures thereof. 
     
     
         38 . A transdermal delivery system according to  claim 36  comprising a plurality of hormones from one or more of these groups preferably a contraceptive active agent comprising one or more estrogens and one or more progestins. 
     
     
         39 . A transdermal delivery system according to  claim 37  wherein the drug delivery system comprises on a weight basis from about 0.1 to about 10% of the hormone, from about 0.1 to 12% of the penetration enhancer and from about 70 to 99.8% ethanol, isopropanol or mixture thereof. 
     
     
         40 . A method of transdermal administration of an active agent to an animal subject comprising application to dermal surface of the animal a transdermal system according to  claim 23 . 
     
     
         41 . A method of transdermal administration according to  claim 40  wherein the animal subject is in need of male hormone replacement in testosterone deficient hypogonadal men, female hormone replacement therapy for postmenopausal women, androgen replacement therapy for females lacking libido using an androgen such as testosterone, male contraception and female contraception. 
     
     
         42 . A transdermal delivery system according to  claim 23  further comprising a spray apparatus comprising a container containing the transdermal composition a spray nozzle and an actuator for delivering a metered dose of spray from the container via the nozzle.