# US 8,784,879 B2 · Transdermal administration of tamsulosin

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- Number: US 8,784,879 B2
- Document ID: US8784879B2
- Status: Granted
- Kind: B2
- Application number: 12/687,586
- Filed: 2010-01-14
- Published: 2010-11-18
- Granted: 2014-07-22
- Earliest claimed: 2009-01-14
- Assignees: Corium International, Inc.
- Applicants: Parminder Singh; Eun Soo Lee; Amit K. Jain
- Inventors: Parminder Singh; Eun Soo Lee; Amit K. Jain
- Web page: https://patentgrep.com/patent/US8784879B2

## CPC

- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- 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)}
- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- A61K 9/7023: {Transdermal patches and similar drug-containing composite devices, e.g. cataplasms (galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006)}
- A61K 9/7053: {obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 47/02: Inorganic compounds
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61P 13/08: of the prostate
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

In an aspect of the invention, a composition for making a patch for the transdermal delivery of tamsulosin is provided. The composition comprises (a) at least about 1 wt % tamsulosin or a pharmaceutically acceptable salt of tamsulosin, (b) at least about 40 wt % polyisobutylene adhesive or hydrophobic synthetic rubber adhesive, (c) about 1-20 wt % of an aprotic solvent in which tamsulosin dissolves readily, (d) about 1-20 wt % of an unsaturated fatty acid or an alpha-hydroxy acid or a mixture of unsaturated fatty acids or alpha-hydroxy acids or of both unsaturated fatty acids and alpha-hydroxy acids, (e) a lipophilic permeation enhancer, and (f) a matrix modifier.

## Claims

### Claim 1

A composition for making a patch for the transdermal delivery of tamsulosin, the composition comprising (a) at least 1 wt % tamsulosin or a pharmaceutically acceptable salt of tamsulosin, (b) at least 40 wt % polyisobutylene adhesive or hydrophobic synthetic rubber adhesive, (c) about 1-20 wt % of an aprotic solvent in which tamsulosin dissolves, (d) about 1-20 wt % of an unsaturated fatty acid or an alpha-hydroxy acid or a mixture of unsaturated fatty acids or alpha-hydroxy acids or of both unsaturated fatty acids and alpha-hydroxy acids, (e) a lipophilic permeation enhancer, and (f) a matrix modifier.

### Claim 2 (depends on 1)

The composition of claim 1, wherein at least a portion of the tamsulosin is present in the form of tamsulosin HCl.

### Claim 3 (depends on 2)

The composition of claim 2, further comprising a neutralizing agent.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the neutralizing agent has a pKa equivalent to or higher than that of tamsulosin.

### Claim 5 (depends on 3)

The composition of claim 3, wherein the neutralizing agent comprises an alkali hydroxide, an alkali salt, or an amine.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the neutralizing agent comprises sodium hydroxide or potassium hydroxide.

### Claim 7 (depends on 5)

The composition of claim 5, wherein the neutralizing agent comprises an alkali salt selected from the group consisting of sodium carbonate, potassium carbonate, sodium silicate, and potassium silicate.

### Claim 8 (depends on 4)

The composition of claim 4, wherein the neutralizing agent comprises substituted or non-substituted alkyl amines.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the neutralizing agent comprises ethanolamine and diethanolamine.

### Claim 10 (depends on 3)

The composition of claim 3, wherein the neutralizing agent comprises sodium hydroxide.

### Claim 11 (depends on 1)

The composition of claim 1, comprising at least 50 wt % polyisobutylene adhesive.

### Claim 12 (depends on 1)

The composition of claim 1, comprising at least 50 wt % hydrophobic synthetic rubber adhesive.

### Claim 13 (depends on 1)

The composition of claim 1, wherein the aprotic solvent is selected from the group consisting of dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide and combinations thereof.

### Claim 14 (depends on 1)

The composition of claim 1, wherein the unsaturated fatty acid is a fatty acid with 11 to 21 carbons or a mixture of such fatty acids.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the unsaturated fatty acid comprises oleic acid, linoleic acid, or linolenic acid.

### Claim 16 (depends on 1)

The composition of claim 1, wherein the alpha-hydroxy acid comprises an acid with 1 to 8 carbons with an alpha-hydroxyl group.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the alpha-hydroxy acid is selected from the group consisting of lactic acid, glycolic acid, malic, citric, alpha-hydroxy caprylic acid, alpha-hydroxybutyric acid and combinations thereof.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the lipophilic permeation enhancer is present at about 1-20 wt %.

### Claim 19 (depends on 1)

The composition of claim 1, wherein the lipophilic permeation enhancer is selected from the group consisting of methyl laurate, propylene glycol monolaurate, glycerol monolaurate, glycerol monooleate, lauryl lactate, myristyl lactate and combinations thereof.

### Claim 20 (depends on 1)

The composition of claim 1, wherein the matrix modifier is present at about 4-20 wt % of the composition.

### Claim 21 (depends on 1)

The composition of claim 1, wherein the matrix modifier is selected from the group consisting of fumed silica, colloidal silicon dioxide, cross-linked polyvinylpyrrolidone, soluble polyvinylpyrrolidone, a cellulose derivative, polyacrylamide, polyacrylic acid, a polyacrylic acid salt, kaolin, bentonite and combinations thereof.

### Claim 22 (depends on 1)

A patch comprising an adhesive matrix made by a process which comprises drying the composition of claim 1.

### Claim 23 (depends on 22)

The patch of claim 22, wherein the adhesive matrix after said drying comprises at least 15 wt % liquid.

### Claim 24 (depends on 22)

The patch of claim 22, wherein the adhesive matrix after drying has a coat weight between about 10 mg/cm2 and 50 mg/cm2.

### Claim 25 (depends on 22)

The patch of claim 22, wherein the in vitro delivery range of tamsulosin is at least 1.7-12.7 μg/cm2 per hr.

### Claim 26 (depends on 22)

The patch of claim 22, wherein the adhesive matrix further comprises a nonwoven material.

### Claim 27 (depends on 22)

The patch of claim 22, which in use over a 24-hour period of time is non-irritating or no more than mildly irritating.

### Claim 28 (depends on 22)

The patch of claim 22, wherein the patch maintains self-adhesion for at least 7 days when it is worn.

### Claim 29

A method of manufacturing a transdermal drug-in-adhesive patch for delivery of tamsulosin, comprising the steps of (a) dissolving tamsulosin or a pharmaceutically acceptable salt of tamsulosin in an aprotic solvent, (b) combining the tamsulosin solution with a lipophilic permeation enhancer, an optional organic solvent, and an unsaturated fatty acid, (c) adding to the result of (b) a matrix modifier and homogenizing the resulting solution, (d) mixing the result of (c) with a polyisobutylene adhesive or hydrophobic synthetic rubber adhesive in a suitable solvent.

### Claim 30 (depends on 29)

The method of claim 29, further comprising adding a neutralizing agent to the result of steps (a) or (b).

### Claim 31 (depends on 29)

The method of claim 29, further comprising solvent casting the result of step (d).

### Claim 32 (depends on 29)

The method of claim 29, resulting in a weight ratio of tamsulosin to the cast, dried matrix of at least 1 wt %.

### Claim 33 (depends on 29)

The method of claim 29, where the aprotic solvent is selected from the group consisting of dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide and combinations thereof.

### Claim 34 (depends on 29)

The method of claim 29, wherein the pharmaceutically acceptable salt of tamsulosin is tamsulosin hydrochloride.

### Claim 35 (depends on 1)

A method of treating a urological condition, comprising administering to a patient suffering from or in danger of developing such a condition a transdermal patch comprising a tamsulosin-containing composition of claim 1.

### Claim 36

A composition for making a patch for the transdermal delivery of an active agent which has poor solubility in an adhesive matrix, the composition comprising (a) at least 1 wt % the active agent or a pharmaceutically acceptable salt of the active agent, (b) at least 40 wt % polyisobutylene adhesive or hydrophobic synthetic rubber adhesive, (c) about 1-20 wt % of an aprotic solvent in which the active agent dissolves readily, (d) about 1-20 wt % of an unsaturated fatty acid or an alpha-hydroxy acid a mixture of unsaturated fatty acids or alpha-hydroxy acids or of both unsaturated fatty acids and alpha-hydroxy acids, (e) a lipophilic permeation enhancer, and (f) a matrix modifier.

### Claim 37

A transdermal delivery system comprising tamsulosin or a pharmaceutically acceptable salt thereof and an alpha-hydroxy acid, wherein the molar ratio of alpha-hydroxy acid to tamsulosin is at least 0.05:1.

### Claim 38

A transdermal delivery system comprising tamsulosin or a pharmaceutically acceptable salt thereof and DMSO, wherein the ratio of the cumulative delivery of tamsulosin to cumulative delivery of DMSO is
at least 0.05 during the period from 72 to 120 hours, and
at least 0.08 during the period from 120 to 168 hours.

### Claim 39 (depends on 38)

The transdermal delivery system of claim 38, wherein the ratio of the cumulative delivery of tamsulosin to the cumulative delivery of DMSO is
no more than about 0.15 in the first 72 hours,
no more than about 0.38 in the first 120 hours, and
no more than about 0.60 in the 168 hour period.

### Claim 40 (depends on 1)

The composition of claim 1, wherein at least a portion of the tamsulosin is present in the form of tamsulosin free base.