Transdermal and/or topical delivery system comprising clobazam

• US 10,624,901 B2
• Filed: 09/18/2019
• Issued: 04/21/2020
• 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): Chang, Kyung S
• Application Number:
  US16/574,684
• Publication Number:
  US 20200009154A1
• Time in Patent Office: 216 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 method of treating epilepsy comprising the following steps:

selecting a patient in need of such treatment;

applying to the skin of the patient a transdermal drug delivery system (TDDS) 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,

thereby treating epilepsy in the patient.

2. The method of claim 1, wherein the epilepsy is the Lennox-Gastaut Syndrome (LGS).

3. The method 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.

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

5. The method 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.

6. The method 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.

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

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

10. The method of claim 1 wherein the active substance area is in a matrix selected from the group consisting of a plastic or synthetic resin matrix, a pressure-sensitive adhesive matrix, wherein 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, acrylic, polyisobutylene, hot-melt adhesive, mixtures of esters of hydrogenated colophony with cellulose derivatives, and combinations thereof.

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

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

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

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

15. The method of claim 1 wherein the TDDS is a gel formulation wherein the glycol is hexylene glycol.

16. The method of claim 1 wherein the TDDS is a gel formulation wherein the gelling agent is hydroxypropyl cellulose.

8. The active substance area containing the clobazam is a single, double-, or multilayered active substance matrix.