TRANSDERMAL DELIVERY SYSTEM

• US 20130317122A1
• Filed: 05/06/2013
• Published: 11/28/2013
• Est. Priority Date: 11/02/2007
• Status: Active Grant

• Current Assignee: Acrux DDS Pty Ltd (Acrux Limited)
• Original Assignee: Acrux DDS Pty Ltd (Acrux Limited)
• Inventors: Setiawan, Kerrie, Watkinson, Adam
• Granted Patent: US 9,078,810 B2
• Time in Patent Office: Days
• US Class Current: 514/785
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61M 35/003 Portable hand-held applicators having means for dispensing or spreading integral media hand-held massage devices with liquid delivery A61H7/003
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/26 : Androgens
• CPC Class Codes: A61P 5/30 : Oestrogens
• CPC Class Codes: A61P 5/44 : Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids

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 C₆ to C₃₀ aliphatic ester of salicylic acid and (ii) polyethylene glycol (PEG) of average molecular weight no more than 300.

Claims

1-22. -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) a C6 to C30 aliphatic 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 C6 to C12 alkyl ester.

25. A transdermal delivery system according to claim 23, wherein the ester of salicylic acid is the ethylhexyl ester.

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 volatile solvent selected from C2 to C4 alkanol.

30. A transdermal delivery system according to claim 23, wherein the volatile solvent is 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 physiologically active agent component which may include one or more physiologically active agents;

(ii) the penetration enhancer component consisting of an 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 will be 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 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 35, 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 23 wherein the drug delivery system comprises on a weight basis from about 0.1 to about 10% of a 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 transdermal delivery system according to claim 23 for transdermal administration of an active agent to an animal subject.

44. 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 spray nozzle.

41. A use of (i) a C6 to C30 aliphatic ester of salicylic acid and (ii) polyethylene glycol (PEG) of average molecular weight no more than 300 in manufacture of a medicament with a physiologically active agent for transdermal administration of the physiologically active agent to an animal by application of the medicament to an area of the dermal surface of the animal.

42. A use according to claim 41, 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, or female contraception.

43. A method of preparing a transdermal delivery system for administration to an area of dermal surface of an animal, the method comprising combining the physiologically active agent and a first penetration enhancer component of a C6 to C30 aliphatic ester of salicylic acid and a second penetration enhancer component of polyethylene glycol of average molecular weight no more than 300.