Transdermal and/or topical delivery system comprising clobazam

• US 10,449,201 B2
• Filed: 07/28/2016
• Issued: 10/22/2019
• Est. Priority Date: 08/17/2015
• Status: Active Grant

• Current Assignee: Alpha To Omega Pharmaceutical Consultants, Inc.
• Original Assignee: Alpha To Omega Pharmaceutical Consultants, Inc.
• Inventors: Plakogiannis, Fotios M., McAfee, Donald, Modi, Nisarg
• Primary Examiner(s): Arnold, Ernst V
• Assistant Examiner(s): Chang, Kyung S
• Application Number:
  US15/221,673
• Publication Number:
  US 20170049714A1
• Time in Patent Office: 1,181 Days
• Field of Search: None
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/22 Anxiolytics

Abstract

A Transdermal Drug Delivery System (TDDS) of the reservoir or plaster type for administrating clobazam for the treatment of various types of anxiety and epilepsy, for 1 day, 2 day, 3 day, 4 day, 5 day, 6 day and/or 7-day continuous application.

Claims

1. A Transdermal drug delivery system (TDDS) for administration of clobazam to a patient comprising:

an active substance area or reservoir comprising a pharmaceutical composition comprising

about 4% to about 6% Clobazam;

about 20% to about 25% diethylene glycol monoethyl ether;

about 10% to about 12% triacetin;

about 10% to about 25% of a surfactant selected from the group consisting of caprylocaproyl polyoxyl-8 glycerides, polyethylene glycol sorbitan monolaurate, propylene glycol monolaurate, and mixtures thereof;

about 5% to about 6% Lactic Acid;

about 10% to about 15% glycol;

about 20% to about 35% mixture of dimethylsulfoxide and dimethylisosorbide;

about 0.1% to about 5% gelling agent;

about pH 5.0 to about 6.0, wherein the percentage of components are weight to weight of the composition,

further wherein the TDDS comprises an impermeable backing layer and a releasing membrane, which is covered by a detachable protective layer,

and further wherein the application period of the TDDS is 7 days.

2. The TDDS according to claim 1, wherein the active substance area or reservoir is configured as a polymer matrix system, a liquid system, a gel system, or a pressure sensitive adhesive system.

3. The TDDS according claim 1, wherein the active substance reservoir is constructed in a pouch-shaped system.

4. The TDDS of claim 1, wherein the active substance reservoir is a preparation selected from the group consisting of flowable, viscous, semi-solid, gel-like, liquid preparation, solution, suspension, and emulsion.

5. The TDDS of claim 1 wherein the active substance reservoir is confined on the skin facing side by an active substance permeable membrane and on the opposite side from the skin by an active substance impermeable layer.

6. The TDDS of claim 1, further comprising an active substance permeable membrane which modifies or controls the rate of active substance release.

7. The TDDS of claim 1, characterized in that the clobazam containing area is a single-, double-, or multilayered active substance matrix.

8. The TDDS of claim 1 further comprising an adhesive so that it may be applied as a plaster or bandage.

9. The TDDS of claim 1 wherein the active substance is a matrix selected from the group consisting of a plastic or synthetic resin matrix, a pressure-sensitive adhesive matrix, wherein the basic polymer(s) of this matrix are selected from the group consisting of polymers based on acrylic acid and its esters, isobutylenes, ethylene-vinyl acetate copolymers, natural rubbers, synthetic rubbers, styrene-diene copolymers, styrene-butadiene block copolymers, isoprene block copolymers, acrylonitrile-butadiene rubber, butyl rubber and neoprene rubber, pressure sensitive adhesives based on silicone, hot-melt adhesive, mixtures of esters of hydrogenated colophony with cellulose derivatives, and combinations thereof.

10. The TDDS of claim 1, wherein the active substance reservoir contains a fiber material, a woven fabric or a nonwoven, to which the active substance is adsorbed.

11. The TDDS of claim 1, wherein the TDDS delivers 1-40 mg/day clobazam through the skin to the blood in a subject, wherein the TDDS produces up to 2000 ng/ml plasma concentration.

12. The TDDS of claim 1, wherein clobazam is present in the active substance reservoir either in dissolved or suspended state.

13. The TDDS of claim 4, wherein the composition weight is about 100 mg/cm² to about 500 mg/cm² of active surface area.

14. The gel formulation of claim 1 wherein the glycol is hexylene glycol.

15. The gel formulation of claim 1 wherein the gelling agent is hydroxypropyl cellulose.