Transdermal administration to humans and animals

• US 5,332,577 A
• Filed: 04/30/1992
• Issued: 07/26/1994
• Est. Priority Date: 12/27/1988
• Status: Expired due to Term

• Current Assignee: Transdermal Biotechnology, Inc.
• Original Assignee: DermaMed s.r.o.
• Inventors: Rubinstein, Yosef, Gertner, Avi
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Bawa, Raj
• Application Number:
  US07/876,153
• Time in Patent Office: 817 Days
• Field of Search: 424/449, 424/443, 424/444, 424/447, 424/484, 424/DIG. 14, 514/843, 514/887
• US Class Current: 424/449
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: Y10S 424/14 Topical contraceptives and spermacides

Abstract

A pharmaceutical composition for use in the transdermal administration of a medicament to both humans and animals, which composition comprises at least ingredients (1) and (2) of the following ingredients (1), (2) and (3), namely: (1) an effective amount of a medicament adapted for transdermal administration; (2) a transdermally transporting effective amount of a carrier for the medicament, which carrier is selected from semisolids and liquids at ambient temperatures, and which carrier comprises at least one compound selected from esters of C_8-24 fatty acids, pharmaceutically acceptable aliphatic polyhydroxy compounds and non-volatile paraffins; (3) an optional medicament selected from antiinflammatory agents and antihistamines, effective to mitigate any skin-incompatibility characteristic which may otherwise be present. Administration is preferably by means of a matrix which comprises a porous, absorbent, perforate and flexible laminar solid support, having the composition absorbed thereon. The invention includes a device for use in transdermal administration, which comprises such a matrix, preferably included in a multilayer system providing a desired controlled or sustained release pattern for said medicament; as well as apparatus for applying a medicament non-adhesively to the skin of an animal, which comprises a removable enclosure bearing such a matrix or device, the apparatus being arranged for non-invasive mounting onto an animal ear.

Claims

1. A pharmaceutical composition for use in the transdermal administration of a medicament, whereby said medicament is detectable in the bloodstream within two hours after administration, which composition comprises

a medicament adapted for transdermal administration and a pharmaceutically acceptable carrier for the medicament;

the improvement being that the carrier consists essentially of at least one compound selected from the group consisting of esters of C_8-24 fatty acids with at least one aliphatic hydroxy compound containing 2-12 carbon atoms and 2-3 hydroxy groups and the acid component of the ester is selected from caprylic, capric, lauric palmic, stearic, arachidic, behenic, lignoceric, oleic, claidic, petroselinic, linoleic, alpha-linolenic, (9,12,15-octadecatrienoic acid), gamma-linolenic, linolelaidic, arachidic, 11-eicosenoic, 11,14-eicosadienoic, 11,14,17-eicosatrienoic, 8,11,14-eicosatrienoic, arachidonic, 5,8,11,14,17-eicosapentaenoic, erucic and nervonic acids, provided that when said hydroxy compound is glycerol, the esters thereof are selected from diglycerides and triglycerides of at least one C_8-24 fatty acid.

2. A composition according to claim 1, wherein the medicament comprises at least one member selected from the group consisting of reproduction modulating agents, animal growth promoting agents, anthelmintics, antibiotics, antiparasitics, antiinflammatory agents, bronchodilating agents, cardiovascular agents, antiallergic agents and micronutrients.

3. A composition according to claim 1, wherein said aliphatic polyhydroxy compounds are selected from the group consisting of glycerol and propylene glycol.

4. A composition according to claim 1, wherein the carrier for the medicament consists essentially of at least one member selected from the group consisting of diglycerides, triglycerides, and mixtures thereof, of at least one C_8-24 fatty acid.

5. A composition according to claim 2, wherein the medicament comprises at least one member selected from the following sub-groups:

(ia) reproduction modulating agents;

estradiol, flugestone acetate, progesterone, proligestone, melengestrol acetate, medroxyprogesterone, medroxyprogesterone acetate, megestrol acetate and testosterone;

(ib) animal growth promoting agents;

estradiol, megestrol acetate, progesterone, testosterone, trenbulone and zeranol;

(ii) anthehintics;

levamisole, ivermectin, mebendazole, pyrantel, albendazole, febantel, fenbendazole, fhbendazole, oxybendazole, oxfendazole, thiabendazole, tricalbendazole, and morantel;

(iii) antibiotics;

semisynthetic penicillins, tetracyclines and cephalosporins;

(iv) antiparasitics;

metronidazole, cythioate and fenthion;

(v) antiinflammatory agents;

diclofenac sodium, ibuprofen, indomethacin, betamethazone, fhmethazone and dexamethazone;

(vi) bronchodilating agents;

aminophylline, theophylline, terbutaline and salbutamol;

(vii) cardiovascular agents;

propanolol, metoprolol and clonidine;

(viii) antiallergic agents;

chlorpheniramine and mebhydroline;

(ix) micronutrients;

selenium disulfide and iron dextran.

6. A composition according to claim 5, wherein the acid component of the ester is selected from the group consisting of caprylic, captic, lauric, palmitic, stearic, arachidic, behenic, lignoceric, oleic, elaidic, petroselinic, linoleic, alphalinolenic (9,12,15-octadecatrienoic acid), gamma-linolenic, linolelaidic, arachidic, 11-eicosenoic, 11,14-eicosadienoic, 11,14,17-eicosatrienoic, 8,11,14,-eicosatrienoic, arachidonic, 5,8,11,14,17-eicosapentaenoic, erucic and nervonic acids.

7. A composition according to claim 5, wherein the carrier for the medicament consists essentially of at least one member selected from the group consisting of diglycerides, triglycerides, and mixtures thereof, of at least one C_8-24 fatty acid.

8. A composition according to claim 1, wherein said carrier comprises at least 40% by weight of at least one ester of at least one C_18-24 fatty acid.