# US 2019/0167612 A1 · Pharmaceutical formulation for oral administration with controlled dissolution rate comprising sustained-release pellets containing tamsulosin hydrochloride

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- Number: US 2019/0167612 A1
- Document ID: US20190167612A1
- Status: Published application
- Kind: A1
- Application number: 16/324,648
- Filed: 2017-08-11
- Published: 2019-06-06
- Earliest claimed: 2016-08-12
- Assignees: HANMl PHARM. CO., LTD.
- Applicants: HANMl PHARM. CO., LTD.
- Inventors: Jae Ho KIM; Benjamin Joon LEE; Jin Cheul KIM; Yong II KIM; Jae Hyun PARK; Jong Soo WOO
- Web page: https://patentgrep.com/patent/US20190167612A1

## CPC

- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- A61K 9/1605: {Excipients; Inactive ingredients}
- A61K 9/1611: {Inorganic compounds}
- A61K 9/1635: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/1682: {Processes}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 9/50: Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)}
- A61K 9/5021: {Organic macromolecular compounds}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/4725: containing further heterocyclic rings
- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048})
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 13/08: of the prostate
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

A pharmaceutical formulation for oral administration with a controlled dissolution rate is provided. The formulation contains Tamsulosin hydrochloride-containing sustained-release pellets. The sustained-release pellets include (i) a Tamsulosin hydrochloride, (ii) hydroxypropyl methylcellulose (HPMC), (iii) an acid-resistant acryl polymer, and (iv) two or more kinds of insoluble diluents. A preparation method of the formulation is provided.

## Claims

### Claim 1

A pharmaceutical formulation for oral administration comprising tamsulosin hydrochloride-containing sustained-release pellets, each pellet comprising (i) tamsulosin hydrochloride, (ii) hydroxypropyl methylcellulose (HPMC), (iii) an acid-resistant acrylic polymer, and (iv) two or more kinds of insoluble diluent.

### Claim 2 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the sustained-release pellets each comprise (i) 0.07% by weight to 0.50% by weight of tamsulosin hydrochloride, (ii) 1.0% by weight to 7.0% by weight of hydroxypropyl methylcellulose (HPMC), (iii) 3.0% by weight to 20.0% by weight of an acid-resistant acrylic polymer, and (iv) 70.0% by weight to 95.9% by weight of two or more kinds of insoluble diluent, based on a dry pellet.

### Claim 3 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the hydroxypropyl methylcellulose (HPMC) has a viscosity of 10,000 cPs to 100,000 cPs.

### Claim 4 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the acid-resistant acrylic polymer is selected from the group consisting of Eudragit L30 D-55, Eudragit L100 D-5, Eudragit L12,5, and any combination thereof.

### Claim 5 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the two or more kinds of insoluble diluent are selected from the group consisting of microcrystalline cellulose, talc, titanium dioxide, and any combination thereof.

### Claim 6 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the sustained-release pellets are further coated with an enteric coating agent.

### Claim 7 (depends on 6)

The pharmaceutical formulation for oral administration of claim 6, wherein the sustained-release pellets each comprise (i) 0.07% by weight to 0.50% by weight of tamsulosin hydrochloride, (ii) 1.0% by weight to 7.0% by weight of hydroxypropyl methylcellulose (HPMC), (iii) 3.0% by weight to 20.0% by weight of an acid-resistant acrylic polymer, (iv) 70.0% by weight to 93.0% by weight of two or more kinds of insoluble diluent, and (v) 1.5% by weight to 15% by weight of an enteric coating agent, based on a dry pellet.

### Claim 8 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the sustained-release pellets are composed of 65% or more of a pellet of 0.8 μm to 1.4 μm, 15% or more of a pellet of 0.4 μm to 0.8 μm, and less than 5% of a pellet of 0.4 μm or less, based on a diameter of spheronization.

### Claim 9 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the tamsulosin hydrochloride-comprising sustained-release pellets show a dissolution rate of 25% to 55% in 1 hour, as tested according to a paddle method which is dissolution test II in the U.S. Pharmacopoeia (USP) under conditions of 50 rpm, 900 mL of a pH 6.8 solution, and 37° C.

### Claim 10 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the pharmaceutical formulation is a capsule formulation comprising the sustained-release pellets.

### Claim 11 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, comprising 0.2 mg or 0.4 mg of tamsulosin hydrochloride per unit formulation.

### Claim 12 (depends on 1)

The pharmaceutical formulation for oral administration of claim 1, wherein the pharmaceutical formulation is used for the treatment or prevention of benign prostatic hyperplasia.

### Claim 13 (depends on 1)

A method of preparing the pharmaceutical formulation for oral administration of claim 1, the method comprising:
(a) mixing and extruding a mixture comprising (i) tamsulosin hydrochloride, (ii) hydroxypropyl methylcellulose (HPMC), (iii) an acid-resistant acrylic polymer, and (iv) two or more kinds of insoluble diluent to mold the mixture in the form of granules; and
(b) spheronizing the extruded granules using a spheronizer at a rotation speed of about 600 rpm to about 800 rpm for about 10 minutes to about 45 minutes to prepare pellets.

### Claim 14

A hard capsule composite formulation containing tamsulosin hydrochloride comprising:
(A) tamsulosin hydrochloride-containing sustained-release pellets, each pellet comprising (i) tamsulosin hydrochloride, (ii) hydroxypropyl methylcellulose (HPMC), (iii) an acid-resistant acrylic polymer, and (iv) two or more kinds of insoluble diluent; and
(B) a pharmaceutical composition physically separated from the tamsulosin hydrochloride-containing sustained-release pellets, the pharmaceutical composition comprising one or more different pharmaceutically active ingredients and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 14)

The tamsulosin hydrochloride-containing hard capsule composite formulation of claim 14, wherein the one or more pharmaceutically active ingredients are selected from the group consisting of dutasteride, tadalafil, finasteride, solifenacin, a pharmaceutically acceptable salt thereof, and any combination thereof.

### Claim 16 (depends on 1)

A method for preventing or treating benign prostatic hyperplasia, comprising administering orally the pharmaceutical formulation of claim 1 to a subject in need thereof.

### Claim 17 (depends on 2)

A method for preventing or treating benign prostatic hyperplasia, comprising administering orally the pharmaceutical formulation of claim 2 to a subject in need thereof.