Transmucosal administration system for a pharmaceutical drug

Patent metadata

Field	Value
Publication number	US-10716762-B2
Application number	US-201314372878-A
Country	US
Kind code	B2
Filing date	Jan 17, 2013
Priority date	Jan 20, 2012
Publication date	Jul 21, 2020
Grant date	Jul 21, 2020

Abstract

The present invention relates to a transmucosal administration system to administer quinones, benzoquinones, and especially 1,4-benzoquinones, via the oromucosal route.

First claim

That which is claimed:

1. A transmucosal administration system comprising a polymer-based film for attachment to oral mucosa with subsequent release of a pharmaceutical active ingredient molecularly dispersed therein to the mucosa wherein the system contains 0.01 to 80% by weight of idebenone as active ingredient
and a carrier material comprising polyalcohol and/or a cellulose derivative,
wherein the system is a mucoadhesive wafer which dissolves in the mouth,
the system exhibits an AUC 0-360 /mg of the active ingredient concentration in the blood that is greater than that exhibited through administering the active ingredient through the oral route on a dose normalized basis,
and optionally an excipient, with said excipient consisting of one or more of flavorings, colorants, sweeteners, fillers, plasticizers, surface-active substances, solubilizers, disintegrants, solubility enhancers and absorption enhancers.

2. The administration system as claimed in claim 1 , wherein the carrier material comprises cellulose, cellulose derivatives, polyvinyl-alcohol, poly-N-vinylpyrrolidones, vinylpyrrolidone-vinyl acetate copolymers, starch, starch derivatives, gelatine, gelatine derivatives, and combinations thereof.

3. The administration system as claimed in claim 1 , wherein the cellulose derivative is methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose or combinations thereof.

4. The administration system as claimed in claim 1 , wherein said system consists of
50% by weight of active ingredient and 40% by weight polyvinyl alcohol and 10% by weight of sodium carboxymethyl-cellulose as carrier material, or
said system comprises 10% by weight of active ingredient and 90% by weight of hydroxypropylmethylcellulose as carrier material.

5. The administration system as claimed in claim 1 , wherein the film dissolves completely in a period of less than 30 minutes in the mouth.

6. The administration system as claimed in claim 1 , wherein the film dissolves completely in a period of less than 15 minutes in the mouth.

7. The administration system as claimed in claim 1 , wherein a maximum concentration of the active ingredient in the blood is reached in a period of less than 240 minutes after application.

8. The administration system as claimed in claim 1 , wherein a maximum concentration of the active ingredient in the blood is reached in a period of less than 60 minutes after application.

9. The administration system as claimed in claim 1 , wherein a maximum concentration of the active ingredient in the blood is reached at a period of between 5 and 30 min after application.

10. The administration system as claimed in claim 1 , wherein the system contains a suspension comprising 40-50% by weight of the active ingredient and 50-60% by weight of a polyalcohol and/or a cellulose derivative as carrier material.

11. The administration system as claimed in claim 1 , wherein the active ingredient is micronized and the system does not include plasticizer.

12. The administration system as claimed in claim 1 , wherein the system consists of an amorphous presentation consisting of 3-20% by weight of the active ingredient and 80-97% by weight of a water soluble polymer as carrier material.

13. The administration system as claimed in claim 1 , wherein the system consists of an amorphous presentation consisting of 5-10% by weight of the active ingredient and 90-95% by weight of a water soluble polymer as carrier material, and the carrier material is a substituted carbohydrate.

14. The administration system as claimed in claim 1 , wherein the system has a monolayer or double-layer construction.

15. The administration system as claimed in claim 1 , wherein the idebenone is either (i) a suspension in polymer comprising 30-60% by weight of active ingredient or (ii) a solid solution comprising 3-20% by weight of active ingredient and wafers incorporating from 15 to 30 mg of pharmaceutical active ingredient that do comprise absorption enhancer exhibit an AUC 0-360 /mg of the active ingredient in the blood that is 26 to 121 times higher than the AUC 0-360 /mg of a microemulsion containing 300 mg of pharmaceutical active ingredient after dose normalization per mg.

16. A transmucosal administration system as claimed in claim 1 , wherein said idebenone is not within an emulsion, a micro-emulsion or nano-emulsion.

17. A transmucosal administration system wherein the system comprises 3-20% by weight of idebenone as an active ingredient,
80 to 97% by weight of a carrier material comprising polyalcohol and/or a cellulose derivative and wherein the system is a mucoadhesive wafer which dissolves in the mouth,
and, optionally, an excipient,
wherein the active ingredient is present dissolved in the carrier material thereby forming a molecularly dispersed solid solution, and said mucoadhesive wafer containing 15 mg of said molecularly dispersed active ingredient exhibits an AUC 0-360 /mg of the active ingredient in the blood that is 4.75 times higher than the AUC 0-360 /mg of said mucoadhesive wafer containing 30 mg of suspended micronized pharmaceutical active ingredient after dose normalization per mg,
and said optional excipient consists of one or more of flavorings, colorants, sweeteners, fillers, plasticizers, surface-active substances, solubilizers, disintegrants, solubility enhancers and absorption enhancers.

18. The administration system as claimed in claim 17 , wherein the system additionally comprises optional excipient consisting of at least one of flavorings, colorants, sweeteners, fillers, plasticizers, surface-active substances, solubilizers, liquid excipient, disintegrants, solubility enhancers and absorption enhancers.

19. A transmucosal administration system as claimed in claim 17 , wherein said system does not include permeation enhancers.

20. The administration system as claimed in claim 17 , wherein the idebenone is a molecularly dispersed solid solution comprising 3-20% by weight of active ingredient in hydroxypropylmethyl cellulose and wafers that do not comprise absorption enhancer incorporating 15 mg of pharmaceutical active ingredient exhibit an AUC 0-360 /mg of the active ingredient in the blood that is higher than the AUC 0-360 /mg of a microemulsion containing 300 mg of pharmaceutical active ingredient after dose normalization per mg.

21. A method of treat ent for a disease comprising administering an administration system as claimed in claim 1 to a patient, wherein said disease is a mitochondrial disease, a neurodegenerative disease, a neuromuscular disease, a psychiatric disorder, a metabolic disorder, cancer; multiple sclerosis or immune dysfunction.

22. The method of treatment as claimed in claim 21 , wherein
said mitochondrial disease is selected from the group consisting of Leber's hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (DOA), macular degeneration, glaucoma, retinopathy, cataract, optic disc drusen (ODD), mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like symptoms (MELAS), myoclonic epilepsy with ragged red fibers (MERRF), myoneurogenic gastrointestinal encephalomyopathy (MNGIE), Kearns-Sayre syndrome, CoQ10 deficiency, and mitochondrial complex deficiencies (1-5, CPEO);
said neurodegenerative disease is selected from the group consisting of Friedreich's ataxia (FRDA), amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, Huntington's disease,

Assignees

• Lts Lohmann Therapie Systeme Ag
• Santhera Pharmaceuticals Schweitz Ag

Inventors

• Krumme Markus
• Jensen Keith
• Dubach-Powell Judith
• Hausmann Rudolf

Classifications

• A61K47/38

  Cellulose; Derivatives thereof · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K31/717

  Celluloses · CPC title

• A61K31/122

  having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin · CPC title

• A61K9/70

  Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)} · CPC title