Transdermal administration of short or intermediate half-life benzodiazepines

• US 5,225,198 A
• Filed: 08/27/1991
• Issued: 07/06/1993
• Est. Priority Date: 08/27/1991
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Cygnus Therapeutic Systems
• Inventors: Sharma, Kuldeepak, Dunbar, Darth M.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HORNE, LEON
• Application Number:
  US07/750,571
• Time in Patent Office: 679 Days
• Field of Search: 424/449, 424/448, 424/447, 424/443
• US Class Current: 424/443
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• 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 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• 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 9/7061 Polyacrylates

Abstract

Method and laminated composite for administering short or intermediate half-life benzodiazepines such as alprazolamine or triazolam transdermally to treat conditions such as anxiety in the case of alprazolam and insomnia in the case of triazolam. The composite comprises an impermeable backing layer and a reservoir layer containing the benzodiazepine and a permeation enhancer combined with a solvent-based acrylic polymer adhesive with the amounts of benzodiazepine and enhancer being sufficient to cause the benzodiazepine to pass through the skin at a rate in excess of about one μg/cm² /hr.

Claims

1. A method for providing short or intermediate half-life benzodiazepine therapy to a human patient in need of such therapy comprising administering a therapeutically effective amount of the benzodiazepine to the patient transdermally through a predetermined area of intact skin over a sustained time period at a controlled rate in combination with a sufficient amount of a permeation enhancer to enable the benzodiazepine to permeate the area of intact skin at a rate in excess of about one μ

g/cm² /hr said benzodiazepine being selected from the group consisting of alprazalam, bromazepam, iorazepam, oxazepam, temazapam and triazolam, and wherein said permeation enhancer is selected from the group consisting of propylyene glycol monolaurate, glyceryl monooleate, lauryl alcohol, mixed vegetable oil or combinations thereof.

2. The method of claim 1 wherein the benzodiazepine is alprazolam and the alprazolam is administered at a rate of about 0.75 to 6 mg/day.

3. The method of claim 1 wherein the benzodiazepine is triazolam and the triazolam is administered at a rate of 0.1 to 1.0 mg/day.

4. The method of claim 1 wherein the benzodiazepine is alprazolam or triazolam and the enhancer is propylene glycol monolaurate, glyceryl monooleate, lauryl alcohol, mixed vegetable oil, or combinations thereof.

5. The method of claim 1 wherein the area of skin is 20 to 60 cm², the benzodiazepine is alprazolam and the alprazolam is administered at a rate of at least about 100 μ

g/hr.

9. The method of claim 2 wherein the permeation enhancer is a fatty acid ester, a fatty acid, or mixtures thereof.

10. The method of claim 5 wherein the permeation enhancer is a fatty acid ester, a fatty acid, or mixtures thereof.

6. A laminated composite for administering a short or intermediate half-life benzodiazepine to an individual transdermally through a predetermined area of intact skin comprising:

a) a backing layer that is substantially impermeable to the benzodiazepine; and

b) a reservoir layer comprising a solvent-based acrylate adhesive polymer, the benzodiazepine dissolved in said polymer, and a permeation enhancer that increases the permeability of the intact skin to the benzodiazepine dissolved in said polymer, the basal surface of said reservoir being adapted to be adhered to said area of intact skin and wherein the amounts of the benzodiazepine and enhancer in said reservoir layer are sufficient to enable a therapeutically effective amount of the benzodiazepine to be administered at a rate in excess of about one μ

g/cm² /hr to the individual through said predetermined area of intact skin over a sustained time period.

7. The laminated composite of claim 6 wherein the benzodiazepine is alprazolam or triazolam and the permeation enhancer is propylene glycol monolaurate, glyceryl monooleate, lauryl alcohol, mixed vegetable oil, or combinations thereof.

8. The laminated composite of claim 6 wherein the benzodiazepine constitutes 1 to 10% by weight of the reservoir lamina and the permeation enhancer constitutes 2 to 20% by weight of the reservoir lamina.