FORM 2
THE PATENTS ACT.1970
(39 of 1970)
&
The Patent Rules, 2003
COMPLETE SPECIFICATION
[Section 10. and Rule 13]
Title "EXTENDED RELEASE FORMULATION OF PRAMIPEXOLE"
Applicant
Name: Torrent Pharmaceuticals Limited
Nationality: Indian
Address: Torrent House, Off Ashram Road. Near Dinesh
Hali, Ahmedabad 380 009, Gujarat, India
The following specification particularly describes the nature of the invention and the manner in which it is to be performed:

EXTENDED RELEASE FORMULATION OF PRAMIPEXOLE FIELD OF INVENTION:
The present invention relates to stable extended release formulation comprising Pramipexol or a pharmaceutical])' acceptable salt thereof in a matrix comprising at least one neutral polymer with Dicalcium phosphate and further excipients, wherein the resulting extended release formulation provides pH-dependent release characteristics in vitro/in vivo, characterized in that the said formulation docs not contain water swelling anionic polymer.
BACKGROUND OF THE INVENTION
Pramipexole is a known dopamine D2 receptor agonist. It is also pharmacologically unique in that it is a full agonist and has receptor selectivity for the dopamine D2 family of dopamine receptors.
The salt form commonly used is pramipexole dihydrochloride monohydrate (molecular formula C101121Cl2N3OS; relative molecular mass 302.27).
Pramipexole is chemically designated as (S)-2-Amino-4, 5, 6. 7-tetrahydro-6-(propylamino) benzothiazole and has the molecular formula C10H17N3S and a relative molecular mass of 211.33. The chemical formula is as follows:


Pramipexole dihydrochloride monohydrate is a white to off-white, tasteless. crystalline powder. Melting occurs in the range of 296°C to 301°C. with decomposition. The substance is more than 20% soluble in water, about 8% in methanol, about 0.5% in ethanol. and practically insoluble in dichloromethane. Pramipexole is a chiral compound with one chiral centre.
Pramipexole dihydrochloride monohydrate is a highly soluble compound. Water solubility is more than 20 mg/ml and solubility in buffer media is generally above 10 mg/ml between pH 2 and pH 7.4. Pramipexole dihydrochloride monohydrate is not hygroscopic, and of highly crystalline nature. Under milling the crystal modification (monohydrate) does not change. Pramipexole is very stable in the solid state, yet in solution it is light sensitive,
Pramipexole is the active ingredient in a product marketed as extended release tablets under the brand name M1RAPEX' ER, indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease and containing the excipients hypromellose, corn starch, carbomer homopolymer. colloidal silicon dioxide, and magnesium stearate.
In Europe, pramipexole is marketed in prolonged release tablets, using the brand name MIRAPEX® ER. It can be used alone or in combination with levodopa. The tablets are taken once a day. with or without food MIRAPEX'® ER has displayed pH dependent release profile in vitro/ in vivo.
However, it has proved difficult to formulate a dosage form having a suitable combination of modified, extended or sustained- release and handling properties. where the drug is one having relatively high solubility, as in the case of pramipexole dihydrochloride. It is further difficult to formulate sustained release composition having pH dependent release profile for vary highly soluble drugs.

There are a number of approaches described in prior art to provide controlled release pharmaceutical compositions of pramipexole.
EP1531814 concerns dispersing an orally deliverable sustained-release tablet composition comprising a water-soluble salt of pramipexole in a matrix. It further comprises a hydrophilic polymer and a starch having a tensile strength of at least about 0.15 kNcm-2
EP1536792 concerns an oral formulation of pramipexole. which, on average, and in a single dose per day in vitro release profile, does not dissolve more than 20% within 2 hours, and of which the in vivo absorption is more than 20% within 2 hours and/or more than 40% within 4 hours.
US patent Publication No. US20070l29329 discloses a stabilized pharmaceutical composition of Pramipexol comprising one or more dextrin.
WO2009109990 discloses a pharmaceutical composition comprising a mixture of pramipexole or its pharmaceutically acceptable salts or its hydrates or solvates thereof, sugar alcohol (s) and a pharmaceutically acceptable carrier medium substantially free of polyvinyl pyrrolidone.
WO2012002644 describes sustained-release pharmaceutical composition of pramipexole comprising a sustained-release agent and a pharmaceutically acceptable excipient including a stabilizer.
WO 2011148243 discloses extended release formulation comprising pramipexole or pharmaceutically acceptable salts; derivatives; solvates; and isomers thereof, a weak acid and an extended release polymer.
EP1781260 discloses an extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt providing a pH-dependent in

vitro release characteristic with a faster release characteristic in the range of pH < 4.5, and a slower and further on pH- independent release characteristic in the range from pH 4.5 to 7.5. This characteristic release profile was achieved by using combination of anionic and non ionic polymers.
In accordance with the invention it has been surprisingly found that extended release formulation comprising Pramipexol or a phamiaceutically acceptable salt thereof, provides a pH-dependent release characteristic without using anionic polymer.
SUMMARY OF THE INVENTION:
The first embodiment of the present invention is to provide stable extended release formulation comprising Pramipexol or a phamiaceutically acceptable salt thereof, suitable for once daily oral administration.
Another embodiment of the present invention is to provide stable extended release formulation comprising Pramipexol or a pharmaceutically acceptable salt thereof in a matrix comprising at least one neutral polymer with Dicalcium phosphate and further excipients, wherein the resulting extended release formulation provides pH-dependent release characteristic in vitro/in vivo, characterized in that the said formulation does not contain water swelling anionic polymer.
Also preferred is an extended release formulation provides a pH dependent release in the range of pH<4.5. and a pH-independent release rate in the range from pH 4,5 to 7.5 characterized in that the said formulation does not contain water swelling anionic polymer.
In one of the preferred embodiment neutral polymer is water swelling and/or non swelling in nature.

In one of the embodiment of the present invention, water swelling neutral polymer is hydroxypropyl methylcellulose.
In one of the embodiment of the present invention, non swelling neutral polymer is Ethyl cellulosc.
One of the preferred embodiments of the present invention is to provide the stable extended release formulation comprising Pramipexol or a pharmaceutically acceptable salt thereof in a matrix comprising
(a) Pramipexole or a salt thereof 0.05 to 5%
(b) Water swelling and/or non swelling neutral polymer 10.0 to 75%
(c) DiCalcium phosphate 15 to 50%
(d) Further excipients ad 100%
In yet another embodiment of the present invention is to provide the stable extended release tablet formulation comprising Pramipexol or a pharmaceutical]}' acceptable salt thereof, can be prepared by roller compaction or direct compression or wet granulation or any other technique known to a skilled person.
In yet another embodiment of the present invention is to provide the use of the stable extended release tablet formulation comprising Pramipexol or a pharmaceutical]}' acceptable salt thereof, for preparing a medical composition for the treatment of Parkinson's disease and complications or disorders associated therewith.

BRIEF DESCRIPTION OF THE DRAWING:
Figure 01 depicts the in vitro dissolution profile of pramipexole dihydrochloride monohydrate tablets of example 01 in pH 1.2. pH 4.5 phosphate buffers and pH 6.8 phosphate buffers.
DETAIL DESCRIPTION OF THE INVENTION:
The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.
Throughout this specification and the appended claims it is to be understood that the words "comprise" and "include" and variations such as "comprises", "comprising", "includes", "including" are to be interpreted inclusively, unless the context requires otherwise. That is, the use of these words may imply the inclusion of an element or elements not specifically recited.
The present invention relates to an extended release formulation comprising Pramipexol or a pharmaceutically acceptable salt thereof, which is suitable for once-daily oral administration, wherein the resulting extended release formulation provides pH-dependent release characteristic in vitro/in vivo. characterized in that the said formulation does not contain water swelling anionic polymer.
As used herein, the term "pramipexole" is understood as covering all forms of pramipexole, the free base as well as pharmaceutically acceptable salts; derivatives; solvates; and isomers thereof. The most preferred form is pramipexole dihydrochloride monohydrate.

The extended release formulation would release drug at substantially constant rate over an extended period of time or a substantially constant amount of drug will be released incrementally over an extended period of time.
The term "excipients" as used herein includes any physiologically inert. pharmacologically inactive material known to one skilled in the art, which is compatible with the physical and chemical characteristics of the particular pramipexole active ingredient selected for use.
The extended release formulation includes tablets, coated tablets, layered tablets. particles, granules, pellets, powders, microparticles, capsules which may be hard gelatin or soft gelatin, caplets, sachets, pellets, spheroids, mini-tablets, beads, microcapsules, lozenges and pills.
The term "pH-independent" indicates that the release characteristic is virtually the same in different pH media.
The term "pH-dependent" refers to a release to the active substance in a manner that is substantially dependent upon the pH of the surrounding medium within the pH ranges normally found in the human gastrointestinal tract.
The first embodiment of the present invention is to provide a stable extended release formulation comprising Pramipexol or a pharmaceutically acceptable salt thereof in a matrix comprising at least one neutral polymer with Dicalcium phosphate and further excipients. wherein the resulting extended release formulation provides a pH-dependent release characteristics in vivo/in vitro. characterized in that the said formulation does not contain water swelling anionic polymer
Also preferred is an extended release formulation provides a pH dependent release in the range of pH<4.5. and a pH-independent release rate in the range

from pH 4.5 to 7.5, characterized in that the said formulation does not contain water swelling anionic polymer
Depending on the particular embodiment the formulation is faster in simulated gastric juice having a pH<4.5, but it is independent from the pH value in the range from pH 4.5 to 7.5.
In one of the preferred embodiment neutral polymer is water swelling and/or non swelling in nature.
The water swelling neutral polymer preferably selected form the group of alky] celluloses, such as methyl cellulose, hydroxyalkylcelluloses. such as hydroxymethyl cellulose, hydroxypropyl cellulose; hydroxyalkyl alkyl celluloses. such as hydroxyethyl methylcellulose and hydroxypropyl methylcellulose: carboxyalkylcelluiose esters; other natural, semi-synthetic, or synthetic di-. oligo-and polysaccharides such as galactomannas, tragacanth, agar, guargum. methacrylate copolymers; polyvinylalcohol: polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate; combinations of polyvinylalcohol and polyvinylpyrrolidone; polyalkylene oxides such as polyethylene oxide and polypropylene oxide and mixture thereof.
Also preferred is an extended release formulation, wherein the water swelling neutral polymer is hydroxypropyl methylcellulose and wherein the content of hydroxypropyl methylcellulose in the matrix is from about 10% to 75% by total weight of the formulation.
The non swelling neutral polymers selected from the group of ethyl cellulose, polyvinyl acetate, polyvinyl chloride, polyethylene, and the like.

Also preferred is an extended release formulation, wherein the non swelling neutral polymer is ethyl cellulose and wherein the content of ethyl cellulose in the matrix is from about 10% to 75% by total weight of the formulation.
As preferred in the present invention Dicalcium phosphate (herein or hereafter referred as DCP) act as a Diluent. DCP is soluble in acidic solution and insoluble in neutral to alkaline pH. The DCP from the said formulation dissolved out when placed in acidic medium leaving space for the drug to diffuse out. However when said formulation is placed in media with pH > 4.5. the DCP in said formulation remains in insoluble form and restrict the movement of API. This results in lower release at higher pH. DCP is preferably included in the range of 15% to 50% by total weight of the formulation.
Besides pramipexole or a salt thereof, and neutral polymer, the formulation of the present invention may also comprises further excipients, i.e. pharmaceutically acceptable formulating agents, in order to promote the manufacture. compressibility, appearance and taste of the preparation. These formulating agents comprises for example, diluents or fillers, glidant, surfactants, binding agent, antioxidant, granulating agents, anti-caking agents, lubricants, flavors, dyes and preservatives. Other conventional excipients known in the art can also be included.
Glidants may include but not limited to colloidal silicon dioxide, magnesium trisilicate. powder cellulose, talc, tribasic calcium phosphate and the like. Colloidal silicon dioxide is preferably included as a glidant in amount up to 2%, by total weight of the formulation.
Lubricants may include but not limited to magnesium stearate, calcium stearate. hydrogenated vegetable oil. magnesium oxide, mineral oil. poloxamer, polyethyleneglycol. polyvinyl alcohol, stearic acid, talc, zinc stearate and the like.

Magnesium stearate is preferably included as a lubricant in amount up to 2%. by-total weight of the formulation.
Surfactant can be used to modulate the drug release rate by changing the hydrophilicity of the dosage form. Surfactant may include but not limited to sodium docusate, sodium lauryl sulfate, polyethylene glycol, lecithin, poloxamer, the polysorbates. the polyoxethylene ethers and the sorbitan esters and the like. Sodium lauryl sulphate is preferably included as a surfactant in amount up to 5%, by total weight of the formulation.
In one of the embodiment of the present invention water swelling and/or non swelling neutral polymer is used having low content of oxidative impurity i.e. HPMC used in the present invention has formaldehyde less than 50 ppm.
Further pramipexol or a pharmaceutically acceptable salt thereof, are sensitive to aldehyde contamination, which is present in water swelling and/or non swelling polymer. It was surprisingly found or observed that use of said polymers with low content of aldehyde reduces the level of degradation impurity.
Also preferred in the present invention, the degradation impurity can further be reduced by using antioxidant, which is selected but not limited to butylated hydroxytoluene. butylated hydroxyanisole. DL-a!pha-tocopherol. propyl gal late. octyl gallate, and the like and mixtures thereof, preferably butylated hydroxy toluene.
As active ingredient, pramipexole or a pharmaceutically acceptable salt thereof may be present in any amount suitable for the desired treatment of a patient. A preferred salt of pramipexole is the dihydrochloride salt, most preferably in the form of monohydrate. Usual amounts are from about 0.1 to about 5 mg pramipexole salt. According to a particularly preferred embodiment e.g. 0.375 mg pramipexole dihydrochloride monohydrate, corresponding to 0.26 mg

anhydrous base, is used extended release tablet formulation according to the present invention. An amount of pramipexole salt, expressed as pramipexole dihydrochloride monohydrate equivalent of about 0.05% to about 5% by weight of total composition.
One of the preferred embodiments of the present invention is to provide the extended release formulation comprising Pramipcxol or a pharmaceutically acceptable salt thereof in a matrix comprising
(a) Pramipexole or a salt thereof 0.05 to 5%
(b) Water swelling and/or non swelling neutral polymer 10.0 to 75%
(c) Dicalcium phosphate 15 to 50%
(d) Further excipients ad 100%
Particularly preferred an extended release formulation comprises pramipexole dihydrochloride monohydrate, dicalcium phosphate, sodium lauryl sulfate, HPMC, Ethyl cellulose, colloidal silicon dioxide and magnesium stearate.
It is preferred that no coating is present on the tablet formulation according to the present invention. However, the extended release tablet of the invention may comprise a non functional coating. The term ''nonfunctional" in the present context means having no substantial effect on release properties of the tablets.
One of the embodiments of present invention is to provide an extended release formulation comprising Pramipexol or a pharmaceutically acceptable salt thereof, can be prepared by direct compression, dry compression (roller compaction), or by wet granulation. Tablets can be prepared by a direct compression technique. using powder blends. Granules can be formed by any processes, using operations such as one or more of dry granulation, wet granulation, extrusion-

spheronization. and the like. Granulation of active ingredients, optionally together with one or more pharmaceutically acceptable excipients such as diluents or fillers, can be carried out in equipment such as planetary mixers, rapid mixer granulators (RMG). fluid bed processors, and the like. Alternatively. powder blends can be compacted using a roller compactor and then milled to produce granules that are suitable for compression. The granules or pellets obtained may further be compressed into tablets or filled into capsules. Tablets and mini-tablets can be filled into capsules, using techniques that are known in the art.
One of the preferred embodiments of present invention is to provide an extended release formulation comprising Pramipexol or a pharmaceutical!}' acceptable salt thereof, can be prepared by the roller compaction, which comprises the following steps:
1. Either a portion and/or full of the excipient(s) were sifted & mixed in RMG.
2. Binder solution was prepared by dissolving Pramipexol dihydrochloride monohydrate with the portion and/or full of the excipient(s) in granulating liquid, preferably purified water.
3. Granulated the mixture obtained in step-1 with binder solution to form wet mass, dried it & get free flowing powder.
4. Powder obtained in step-3 blended with either a portion or full of the neutral polymer(s) & compacted in roller compactor.
5. Compacted mass obtained in step-4 was optionally milled to get granules of desired size.
6. Granules obtained in step-5 again blended with remaining polymer(s) and excipient(s) followed by lubricated with magnesium stearate.
7. Compress the lubricated blend to tablets using suitable punches & compression machine

One of the preferred embodiments of present invention is to provide an extended release formulation comprising Pramipexol or a pharmaceuticalty acceptable salt thereof, can be prepared by the direct compression, which comprises the following steps:
1. Pramipexole dihydrochloride tnonohydrate with neutral polymer(s) and/or all the excipient(s) were co sifted & mixed until homogenous blend is obtained.
2. Lubricated the blend obtained in step-] with lubricant
3. Compress the lubricated blend to tablets using suitable punches & compression machine.
In yet another embodiment of the present invention is to provide the use of an extended release tablet formulation comprising Pramipexol or a pharmaceutically acceptable salt thereof, for preparing a medical composition for the treatment of Parkinson's disease and complications or disorders associated therewith.
The invention will be further illustrated by the following example, however, without restricting its scope to these embodiments.
Examples:
Example: 1 Extended release formulation of Pramipexol 0.26 mg
The Pramipexol tablet in this example contains 0.375 mg of pramipexole dihydrochloride monohydrate. corresponding to 0.26 mg of pramipexole free. anhydrous base.

Formula:

Ingredients Mg/Tablet
DCP 98.625
Pramipexole 2HC1 H20 0.375
SLS 2.00
HPMC K4M 150.00
HPMCK15M 75.00
Mg stearate 2.00
Colloidal Si02 2.00
Total Weight (mg) 330.000
Procedure:
1. Dicalcium phosphate. Pramipexole dihydrochloride monohydrate. SLS, HPMC K4M, HPMC K15M were co sifted & mixed until homogenous blend is obtained.
2. Lubricated the blend obtained in step-1 with Colloidal Silicon dioxide and Magnesium stearate,
3. Compress the lubricated blend to tablets using suitable punches & compression machine.
Example: 2 Extended release formulation of Pramipexol 0.52 mg
The Pramipexol tablet in the example contains 0.75 mg of pramipexole dihydrochloride monohydrate, corresponding to 0.52 mg of pramipexole free. anhydrous base.

Formula:

Ingredients Mg/Tablet
DCP 98.25
Pramipexole 2HC1 H2O 0.750
SLS 2.00
HPMC K4M 150.00
HPMCK15M 75.00
Mg stearate 2.00
Colloidal SiO2 2.00
Total Weight (mg) 330.000
Procedure:
1. Dicafcium phosphate. Pramipexole d[hydrochloride monohydrate. SLS. HPMC K4M. HPMC K15M were co sifted & mixed until homogenous blend is obtained.
2. Lubricated the blend obtained in step-1 with Colloidal Silicon dioxide and Magnesium stearate.
3. Compress the lubricated blend to tablets using suitable punches & compression machine.
Example: 3 Extended release formulation of Pramipexol 0.26 mg
The Pramipexol tablet in the example contains 0.375 mg of pramipexole dihydrochloride monohydrate. corresponding to 0.26 mg of pramipexole free. anhydrous base.

Formula:

Ingredients Mg/ tablet
Dicalcium phosphate 95.675
Pramipexole dihydrochloridc monohydrate 0.375
Sodium lauryl sulphate 2,00
HPMC 3 cps 3.30
HPMC K4M CR 150.00
HPMCK15MCR 75.00
Mg stearate 1.650
Colloidal Si02 2.00
Total Weight (mg) 330.000
Procedure:
1. Dicalcium phosphate and SLS were sifted & mixed in RMG.
2. Binder solution was prepared by dissolving Pramipexol dihydrochloridc monohydrate with the portion and/or full of the I-1 PMC in purified water.
3. Granulated the mixture obtained in step-1 with binder solution to form wet mass, dried it & get free flowing powder.
4. Powder obtained in step-3 blended with either a portion or full of the HPMC K4M & compacted in roller compactor.
5. Compacted mass obtained in step-4 was optionally milled to get granules of desired size
6. Granules obtained in step-5 again blended with HPMC K15 M and Colloidal silicon dioxide followed by lubricated with magnesium stearate.

7. Compress the lubricated blend to tablets using suitable punches & compression machine.
Example: 4 Extended release formulation of Pramipexol 0.52 mg
The Pramipexol tablet in the example contains 0.75 mg of pramipexole dihydrochloride monohydrate. corresponding to 0.52 mg of pramipexole free. anhydrous base.
Formula:

Ingredients Mg/tablet
Dicalcium phosphate 95.30
Pramipexole dihydrochloride monohydrate 0.750
Sodium lauryl sulphate 2.00
HPMC 3 cps 3.30
HPMCK4M CR 150.00
HPMCK15MCR 75.00
Mg stearale 1.650
Colloidal Si02 2.00
Total Weight (mg) 330.000
Procedure:
1, Dicalcium phosphate and SLS were sifted & mixed in RMG.
2. Binder solution was prepared by dissolving Pramipexol
dihydrochloride monohydrate with the portion and/or full of the
HPMC in purified water.

3. Granulated the mixture obtained in step-1 with binder solution to form wet mass, dried it & get free flowing powder.
4. Powder obtained in step-3 blended with either a portion or full of the HPMC K4M & compacted in roller compactor.
5. Compacted mass obtained in step-4 was optionally milled to get granules of desired size
6. Granules obtained in step-5 again blended with HPMC K.15 M and Colloidal silicon dioxide followed by lubricated with magnesium stearate.
7. Compress the lubricated blend to tablets using suitable punches & compression machine.
Example: 5 Extended release formulation of Pramipexol 0.26 mg Formula:

Ingredients Mg/tablet
Dicalcium phosphate 89.625
Pramipexole dihydrochloride monohydrate 0.375
Sodium lauryl sulphate 6.00
Microcrystalline cellulose 51.00
Ethyl cellulose 53.00
IPA: Water QS
HPMC K15MCR 36.00
Mg stearate 2.00
Colloidal SiO, 2.00
Total Weight (mg) 240.000

Procedure:
1. Dicalcium phosphate, microcrystalline cellulose, ethyl cellulose and sodium lauryl sulphate were sifted & mixed in RMG.
2. Binder solution was prepared by dissolving Pramipexol dihydrochloride monohydrate in IP A: water
3. Granulated the mixture obtained in step-1 with binder solution to form wet mass, dried it & get free flowing powder.
4. Granules obtained in step-3 again blended with HPMC K15 M and Colloidal silicon dioxide followed by lubricated with magnesium stearate.
5. Compress the lubricated blend to tablets using suitable punches & compression machine.
Dissolution Study of the pramipexole dihydrochloride monohydrate tablets of Example 01
The dissolution profile of the pramipexole dihydrochloride monohydrate tablets of Example 01 was carried out in type 1 dissolution apparatus, basket, at lOOrpm. at a temperature of about 37±0.5°C. in 900ml of 0.1 N HCI, pH 4.5 phosphate buffer and pH 6.8 phosphate buffer. The results of the in vitro dissolution profile are set forth in Table: 01 & illustrated in Figure 01

Table: 01

% Drug release
Time (Hrs) pH1.2
(O.l NHCl) pH4.5
(Phosphate
Buffer) pH6.8
(Phosphate
Buffer)
0 0 0 0
2 35 23 24
6 65 46 48
9 77 59 61
16 91 76 79
24 95 85 89

We Claim:
1. An extended release formulation comprising Pramipexole or a
pharmaceutically acceptable salt thereof in a matrix comprising at least one
neutral polymer, dicalcium phosphate and further excipients.
2. The extended release formulation of claim 1. wherein neutral polymer is water swelling and/or non swelling.
3. The extended release formulation of claim 1, wherein said formulation does not contain water swelling anionic polymer.
4. The extended release formulation of claim 2. wherein water swelling neutral polymer is selected from hydroxypropylcellulose and hydroxypropylmethylcellulose.
5. The extended release formulation of claim 2, wherein the water swelling neutral polymer is hydroxypropyl methylcellulose, and wherein the content of hydroxypropyl methylcellulose in the matrix is from about 10 % to 75% by total weight of the formulation.
6. The extended release formulation of claim 2. wherein the non swelling neutral polymer is selected from ethyl cellulose, polyvinyl acetate, polyvinyl chloride and polyethylene.
7. The extended release formulation of claim 2. wherein the matrix comprising:

(a) Pramipexole or a salt thereof 0.05 to 5 %
(b) Water swelling and non swelling neutral polymer 10.0 to 25 %
(c) Dicalcium phosphate 15 to 50 %
(d) Further excipients ad 100 %

8. The extended release formulation according to claim 1. the resulting formulation providing a pH-dependent release in the range of pH < 4.5. and a pH-independenl release in the range from pH 4.5 to 7.5. characterized in that the said formulation does not contain water swelling anionic polymer.
9. The extended release formulation according to any of the previous claims, wherein the contained amount of pramipexole or pharmaceutically acceptable salt thereof is sufficient to provide a daily dose administered at one time,
10. An extended released formulation comprising Pramipexole or a
pharmaceutically acceptable salt thereof as substantially described and
exemplified herein.