FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
TITLE OF THE INVENTION
"FORMULTION CONTAINING ANTIARRHYTHMIC DRUG
We, BA RESEARCH INDIA LIMITED, of BA Research House, Opposite "Pushparaj Towers", Nr. Judges Bungalows, Bodakdev, Ahmedabad - 380054, Gujarat, India;
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

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FIELD OF INVENTION
Novel pharmaceutical dosage forms providing for therapeutic amount of a pharmaceutically acceptable salt of Amiodarone are provided. The Amiodarone tablet is provided in a pharmaceutically acceptable polymer matrix comprising at least one continuous polydextrose phase and at least one continuous phase of a polymer other than polydextrose The dosage forms are in the form of tablets and such dosage forms have the benefit of overcoming the problem with delivery of Amiodarone which is normally formulated as a parenteral formulation.
BACKGROUND OF THE INVENTION
Antiarrhythmic agents are employed to treat patients suffering from, inter alia,
cardiac contractions that are too rapid, too slow or asynchronous. Generally, antiarrhythmic
agents are classified according to the Vaughan Williams' classification. For example, beta
adrenoreceptor-blocking agents are classified as "Class II" antiarrhythmic agents and
potassium channel blocking agents are classified as "Class III" antiarrhythmic agents.
Amiodarone [(2-butyl-3-benzofuranyl){4-[2-(diethylamino)ethoxy]-3,5-
diiodophenyl}methanone] salts fall within a class of antiarhythmatic drugs with predominantly class III oral administration. It is used for the treatment of arrhythmias including wide range of cardiac tachyarrhythmias including both ventricular and supraventricular arrhythmias. Amiodarone HC1 is provided commercially in tablet form as 'Cordaronel'. Very little work have been carried out in developing alternate solid formulations of Amiodarone though it has been in the market from the sixties. We herein describe a novel formulation of Amiodarone which releases the drug in pulses allowing for greater amount time when the drug is available and also release the drug in a controlled manner.
EMBODIMENTS OF THE PRESENT INVENTION:
It is an important object of the present invention to provide a solid pharmaceutical
dosage form for Amiodarone salts in the form of tablets wherein the drug is present in a pharmaceutically acceptable polymer matrix comprising at least one continuous polydextrose phase and at least one continuous phase of a polymer other than polydextrose.
The subject of the present invention is thus a solid pharmaceutical composition comprising a solid dispersion containing Amiodarone and a pharmaceutically acceptable polymer matrix, characterized in that said pharmaceutically acceptable polymer matrix comprises a blend of (i) polydextrose, in the form of a continuous polydextrose phase, and (ii) at least one polymer other than polydextrose, in the form of a continuous phase of this polymer, the proportion of said polydextrose being at least 10% by weight and the proportion


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of said at least one polymer other than polydextrose being at least 20% by weight, relative to the total weight of said pharmaceutically acceptable polymer matrix.
In particular, the pharmaceutical composition according to the invention is characterized in that it can be obtained by means of a process comprising at least one step consisting in producing a compound containing Amiodarone, said polydextrose and said at least one polymer other than polydextrose, in a mixer and at a mixing temperature of between approximately 50 °C. and approximately 250 °C.
In a further embodiment is provided suitable dosage form of Amiodarone salts for the treatment of cardiac arrhythmias.
DETAILED DESCRIPTION OF THE INVENTION
The subject of the present invention is thus a solid pharmaceutical composition comprising a solid dispersion containing Amiodarone and a pharmaceutically acceptable polymer matrix, characterized in that said pharmaceutically acceptable polymer matrix comprises a blend of (i) polydextrose, in the form of a continuous polydextrose phase, in order to promote the disintegration of the composition in an aqueous medium, and (ii) at least one polymer other than polydextrose, in the form of a continuous phase of this polymer, the proportion of said polydextrose being at least 10% by weight and the proportion of said at least one polymer other than polydextrose being at least 20% by weight, relative to the total weight of said pharmaceutically acceptable polymer matrix.
This pharmaceutical composition can be obtained by means of a process comprising at least one step consisting in producing a compound containing Amiodarine, said polydextrose and said at least one polymer other than polydextrose, in a suitable mixer and at a mixing temperature of between approximately 50 °C. and approximately 250 °C,
The pharmaceutical composition according to the invention is most particularly suitable for oral administration.
According to the invention, the term "solid dispersion" is intended to mean a dispersion containing Amiodarone in a pharmaceutically acceptable polymer matrix, in the form of a solid solution (Amiodarone dispersed in an amorphous state) or in an intermediate form (Amiodarone partly dispersed in the amorphous state and partly in the crystalline state). According to the invention, the term "continuous phase" of a given polymer (polydextrose or other) is intended to mean that said polymer constitutes a fraction of the polymer matrix and is not in the dispersed state, i.e. is spread without discontinuity throughout the three dimensions of the solid dispersion.
The pharmaceutically acceptable polymer matrix of the composition according to the invention thus comprises a blend of at least two continuous polymer phases, i.e. a blend of


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said polydextrose, in the form of a first continuous phase, and of said at least one polymer other than polydextrose, in the form of at least one other continuous phase, these distinct continuous polymer phases not being discretely dispersed in one another.
It has been noted that this characteristic structure of the composition according to the invention results, firstly, from the respective polymer content and, secondly, from the step consisting of the process for producing a compound of the components for said solid dispersion using a suitable mixer such as screw mixer and at a mixing temperature of between 50 °C and approximately 250 °C.
According to the present invention, it is to be noted that the polydextrose, in the form of a continuous polydextrose phase of a polymer matrix also comprises a polymer other than polydextrose, also in the form of a continuous phase, in a pharmaceutical composition comprising a solid dispersion of Amiodarone in such a polymer matrix, which is in particular bicontinuous, as the function of promoting the disintegration of the pharmaceutical composition in an aqueous medium.
According to the present invention the expression "promoting the disintegration of the pharmaceutical composition" is intended to mean the acceleration of the disintegration of the solid dispersion in an aqueous medium. The disintegration capacity is determined according to the disintegration assay described in the European Pharmacopeia.
Without however, wishing to be bound by any theory, the improved disintegration in the stomach, as provided by the presence of the continuous polydextrose phase in the pharmaceutical composition according to the invention, should make it possible to advantageously reduce the risks of local concentrations and therefore, of precipitation of Amiodarone in particular in the gastrointestinal tract.
Polydextrose is a water-soluble amorphous polymer comprising glucose units linked randomly via glucoside bonds of all types (predominantly 1, 6) and also minor contents in particular of glucose and sorbitol units. A polydextrose preparation has been described in particular in patents U.S. Pat. No. 3,766,165 and U.S. Pat. No. 3,876,794 from the company Pfizer Inc., both of which are incorporated herein by reference in their entirety. Polydextrose can, in general, be obtained by means of a process comprising a step consisting of a catalytic condensation reaction using a mixture comprising D-glucose, of sorbitol and an acid catalyst, in particular citric acid or phosphoric acid.
The use of polydextrose was first developed in the food industry, in particular dietetics, given its partial metabolism and therefore its low calorie content. Polydextrose is, for example, mentioned in the "Food Chemicals Codex" (FCC, 4th edition, 1996).


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While the invention has been described by way of examples and in terms of the preferred embodiments, it is to be understood that the invention is not limited to the disclosed embodiments. On the contrary, it is intended to cover various modifications as would be apparent to those skilled in the art. Therefore, the scope of the appended claims should be accorded the broadest interpretation so as to encompass all such modifications.
According to the present invention, the term "polydextrose" is thus intended to mean, of course, a pharmaceutically acceptable polydextrose. In particular, a pharmaceutically acceptable polydextrose preferably has a purity of at least 90% by weight of polydextrose, the remaining components predominantly comprising free glucose, sorbitol, and levoglucosan (1,6-anhydro-D-glucose) units and water, it being possible for the purity to be determined by UV spectrophotometry on a dried substance.
The polydextrose that can be used in the composition according to the invention preferably has a molecular weight of at most 22 000 g/rnol, as measured in a known manner by gel permeation chromatography (or "exclusion chromatography") with a refractometric detector.
In particular, the polydextrose that can be used in the composition according to the invention has an average molecular weight of between 150 and 5000, in particular between 1000 and 2000.
The polymer "other than polydextrose" included in the polymer matrix of the composition according to the invention may be any polymer that can be used in the solid dispersions of the prior art, and of course a polymer other than polydextrose as defined above.
In particular, said at least one polymer other than polydextrose is selected from the
group comprising: cellulose-based polymers, such as alkylcelluloses, in particular
methylcellulose, such as hydroxyalkylcelluloses, in particular hydroxymethylcellulose,
hydroxyethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose and weakly
substituted hydroxypropylcellulose, such as hydroxyalkylalkylcelluloses, in particular
hydroxyethylmethylcellulose and hydroxypropylmethylcellulose, such as
carboxyalkylcelluloses, in particular carboxymethylcellulose, such as carboxyalkylcellulose salts, in particular sodium carboxymethylcellulose, such as carboxyalkylalkylcelluloses, in particular carboxymethylethylcellulose, and such as esters of cellulose derivatives, in particular hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate and cellulose acetate phthalate; vinyl homo- and copolymers, such as N-vinylpyrrolidone polymers, in particular povidone, copovidone and polyvinyl alcohol; acrylic and methacrylic polymers, such as those sold under the name Eudragit(R); chemically


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modified starches, in particular starches derived from starches extracted in particular from maize, from potato, from rice, from wheat or from tapioca; pectins; chitin derivatives such as chitosan; polymers of natural origin, such as gum tragacanth, gelatin, sodium alginate, pullulan, gum arabic, guar gum, agar-agar and xanthan gum; polyalkylene oxides, such as polyethylene oxides, polypropylene oxides and copolymers of ethylene oxide and of propylene oxide; and blends thereof.
More particularly, said at least one polymer other than polydextrose is selected from
the group comprising methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose,
hydroxypropylcellulose, hydroxybutylcellulose, weakly substituted hydroxypropylcellulose,
hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose,
sodium carboxymethylcellulose, carboxymethylethylcellulose, hyd
roxypropylmethylcellulose phthalate, hyd roxypropylmethylcellulose acetate succinate, cellulose acetate phthalate, povidone, copovidone, polyvinyl alcohol, acrylic and methacrylic polymers, such as those sold under the name Eudragit(R), starches derived from starches extracted from maize, from potato, from rice, from wheat or from tapioca, pectins, chitosan, gum tragacanth, gelatin, sodium alginate, pullulan, gum arabic, guar gum, agar-agar, xanthan gum, polyethylene oxides, polypropylene oxides, copolymers of ethylene oxide and of propylene oxide, and blends thereof.
The polymer other than polydextrose can be used in the composition according to the invention is in particular selected from the group comprising hydrophilic polymers other than polydextrose, and blends thereof, and is more particularly selected from the group comprising: hydroxypropylcellulose, hydroxyethylcellulose, cationic copolymers of dimethylaminoethyl methacrylates and of neutral methacrylic esters, anionic copolymers of methacrylic acid and of methacrylic acid esters, hydroxypropylmethylcellulose acetate succinate, polyethylene glycols, preferably those having a molecular weight greater than 1500; copovidone, and blends thereof.
According to a specific embodiment of the present invention, the polymer matrix of the composition according to the invention comprises only two continuous polymer phases, i.e. a first continuous polydextrose phase and a second continuous phase of said at least one polymer other than polydextrose, the pharmaceutical composition according to the invention thus characteristically exhibiting a polymer matrix with a bicontinuous structure essentially consisting of a continuous polydextrose phase and of a continuous phase of said at least one polymer other than polydextrose.
More particularly, the pharmaceutical composition according to the invention is characterized in that said pharmaceutically acceptable polymer matrix has a bicontinuous


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structure essentially consisting of a continuous phase of said polydextrose and of a continuous phase of said at least one polymer other than polydextrose selected from the group comprising hydrophilic polymers and blends thereof, as described above, i.e. more particularly the group comprising hydroxypropylcellulose, hydroxyethylcellulose, cationic copolymers of dimethylaminoethyl methacrylates and of neutral methacrylic esters, anionic copolymers of methacrylic acid and of methacrylic acid esters, hydroxypropylmethylcellulose acetate succinate, polyethylene glycols, copovidone, and blends thereof.
In particular, the pharmaceutical composition according to the invention is characterized in that the proportion of said polydextrose is between approximately 10% and approximately 80% by weight, and in that the proportion of said at least one polymer other than polydextrose is between approximately 20% and approximately 80% by weight, relative to the total weight of the pharmaceutically acceptable polymer matrix.
According to a specific embodiment, the weight ratio of said polydextrose to said at least one polymer other than polydextrose, in the polymer matrix of the pharmaceutical composition according to the invention, is between approximately 20:80 and approximately 50:50.
The proportion of said pharmaceutically acceptable polymer matrix, in the pharmaceutical composition according to the invention, may in particular be between approximately 50% and approximately 99.9% by weight, relative to the total weight of the composition.
The pharmaceutical composition according to the invention can also comprise any component known to those skilled in the art for a pharmaceutical composition, in particular those for a pharmaceutical composition comprising a solid dispersion. In particular, the pharmaceutical composition according to the invention is characterized in that said compound produced in a screw mixer can also contain at least one component selected from the group comprising plasticizers, demolding agents or lubricants, fluidifying agents, antioxidants, preserving agents, dyes, flavorings, sweeteners, wetting agents, buffers, adsorbents, absorption promoters, bioadhesive agents, disintegrating agents and mixtures thereof.
As indicated above, it has been noted that the characteristic structure of the composition according to the invention results not only from the respective contents of polymers (at least 10% by weight, relative to the total weight of said pharmaceutically acceptable polymer matrix) but also from the step consisting of the process consisting in producing a compound of the components for said solid dispersion using a screw mixer and at a mixing temperature of between approximately 50 °C. and approximately 250 °C.


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More particularly, said mixing temperature is between approximately 80 °C and approximately 200 °C, and even more particularly between approximately 100 °C and approximately 160 °C.
This mixing temperature is preferably regulated at a temperature that is suitable for Amiodarone. It can, for example, be decreased so as to prevent too great a disintegration of Amiodarone, for a given polymer matrix, according to techniques known to those skilled in the art, in particular by introduction of at least one plasticizer, in order to reduce the glass transition temperature of the polymer matrix, such as triethyl citrate, ethylene glycol, triethylene glycol, polyethylene glycol, polypropylene glycol, copolymers of ethylene glycol and of propylene glycol, a poloxamer or water.
The mixing temperature can be obtained in particular by virtue of heating means integrated into the mixer.
The components of the compound intended to be produced in said mixer preferably a screw mixer, i.e., Amiodarone, said polydextrose and said at least one polymer other than polydextrose, can be introduced into the mixer individually and/or as a mixture of at least some of them. For example, the components can be introduced in the form of a simple homogenous preliminary mixture or "physical mixture", produced at ambient temperature (approximately 25 °C.) in a conventional mixer.
The mixer can thus be in particular selected from the known devices for extrusion or injection molding of plastics. Various geometries may be suitable, in particular according to the composition of the compound.
According to a particularly preferred embodiment of the present invention, said mixer is an extrusion device. More particularly, said step consisting in producing said compound in an extrusion device can be advantageously followed by at least one step consisting in forming the extruded compound, at the temperature of the extruded compound or after cooling of the extruded compound to a suitable forming temperature, selected from the group comprising calendering, spinning and cutting steps, and combinations of these steps.
According to another particularly preferred embodiment of the present invention, said mixer is an injection-molding device.
If necessary, the mixing step in the mixer can be preceded by a step consisting of physical mixing at a suitable temperature, in particular between ambient temperature (approximately 25 °C.) and the temperature of the compound in the mixer, for a period of time sufficient to obtain a homogeneous physical mixture, in particular with a view to facilitating the feeding of said mixer.


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Irrespective of the mixer used, the pharmaceutical composition according to the invention is more particularly characterized in that said process also comprises, after cooling to a suitable temperature for sufficiently solidifying the compound obtained, at least one step selected from the group comprising milling and cuffing steps, and combinations of these steps.
The composition can further comprise a coating, such as those known to those skilled in the art, in particular, for improving the appearance and/or the taste and/or providing an effect of modified release of Amiodarone.
EXAMPLE 1
Molded Tablet with a Polydextrose and Copovidone (50:50) Polymer Matrix and 0.5% of Amiodarone
A physical mixture containing 0.5% by weight of Amiodarone, 49.75% by weight of copovidone (obtained from commercial sources) and 49.75% by weight of polydextrose (obtained from commercial sources) is prepared. The physical mixing is carried out at ambient temperature (approximately 25 °C.) in a mixer for 45 minutes, so as to obtain a homogeneous physical mixture.
An injection-molding machine is fed with this physical mixture. The operating parameters are as follows: nozzle temperature: 160 °C; hot runner temperature: 160 °C.
The mold used is such that it makes it possible to obtain a molded tablet having a size and shape substantially identical to those of a gelatin capsule of size 0. After cooling to ambient temperature, the molded tablets with a polydextrose and copovidone polymer matrix thus obtained (polydextrose : copovidone weight ratio of 50:50) have an average mass of 1053 mg, each molded tablet containing a dose of approximately 5 mg of Amodiarone. COMPARATIVE EXAMPLE 1 Molded Tablet with a Copovidone Polymer Matrix and with 0.5% of Amodiarone
A physical mixture containing 0.5% by weight of Amodiarone and 99.5% by weight of copovidone is prepared. The physical mixing is carried out at ambient temperature (approximately 25 °C.) in a mixer, for 60 minutes, so as to obtain a homogeneous physical mixture.
An injection-molding machine is fed with this physical mixture. The operating parameters are as follows: nozzle temperature: 160 °C; hot runner temperature: 160 °C.


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The mold used is such that it makes it possible to obtain a molded tablet having a size
and shape substantially identical to those of a gelatin capsule of size 0.
After cooling to ambient temperature, the molded tablets with a copovidone polymer
matrix thus obtained have an average mass of 939 mg, each molded tablet containing a dose
of 5 mg of Amodiarone
COMPARATIVE EXAMPLE 2
Molded Tablet with a Polydextrose Polymer Matrix and with 0.5% of Amodiarone
A physical mixture containing 0.5% by weight of Amodiarone weight of polydextrose
is prepared. The physical mixing is carried out at ambient temperature in a , for 45 minutes,
so as to obtain a homogeneous physical mixture.
An injection-molding machine is fed with this physical mixture. The operating
parameters are as follows:
nozzle temperature: 160 °C;
hot runner temperature: 160 °C.
The mold used is such that it makes it possible to obtain a molded tablet having a size and shape substantially identical to those of a gelatin capsule of size 0. After cooling to ambient temperature, the molded tablets with a polydextrose polymer matrix thus obtained have an average mass of 1150 mg, each molded tablet containing a dose of approximately 5 mg of Amodiarone
EXAMPLE 2
In Vitro Dissolution Tests
The dissolution of Amodiarone molded tablets prepared in example 1 and in comparative examples 1 and 2 above, is studied.
The dissolution kinetics arc measured in paddle devices, with a simulated gastrointestinal dissolution medium at pH 6.5, composed of a mixture of a quarter of a volume of simulated gastric medium without enzymes according to the Pharmacopeia USP XXI (2 g/liter of sodium chloride, the pH of wluch is adjusted to pH-1.2 with 11.6 M hydrochloric acid) and three quarters of a volume of the simulated intestinal medium without enzymes according to the Pharmacopeia USP XXI (6.8 g/liter of monopotassium phosphate, the pH of which is adjusted to 7.5 with 10 M sodium hydroxide), at 37 °C. and with paddle stirring at 75 rpm. The concentration of Amodiarone dissolved in the dissolution medium is determined by taking a sample of 1 ml at the indicated time, each sample being filtered through a 5 [small mu, Greekjm membrane and then assayed by liquid chromatography.
Three measurements are taken each time, in order to deduce therefrom a mean value of percentage dissolution for a given time. The results (means) are reported in the following


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table 1. They are expressed as percentage of Amodiarone dissolved, at a rate of 2 molded tablets per bowl containing 500 ml of dissolution medium.
Table 1

Dissolution of Amodiarone using the molded tablets with copovidone and/orpolydextrose polymer matrix
% dissolution of Amodiarone
Time(inmin) Molded tablet of comparative Example 1 Molded tablet of comparative Example 2, Molded tablet of comparative Example 3
15 22 48 38
30 41 56 63
120 68 59 85.5
180 85 58 92
240 84 50 90.6
300 84.5 46 91
According to these results, the molded tablets with a copovidone and polydextrose (50:50) polymer matrix according to the invention provide a solubility of Amodiarone, at least from 30 minutes, that is clearly greater than that obtained with each of the molded tablets with a polymer matrix of copovidone alone and the molded tablets with a polymer matrix of polydextrose alone. Similar results were obtained with different batches of similar composition.


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We claim:
1. A pharmaceutical composition comprising a solid dispersion comprising Amodiarone and a pharmaceutically acceptable polymer matrix, wherein said pharmaceutically acceptable polymer matrix comprises a blend of (i) polydextrose, in the form of a continuous polydextrose phase, and (ii) at least one polymer other than polydextrose, in the form of a continuous phase of said at lease one polymer, the proportion of said polydextrose being at least 20% by weight and the proportion of said at least one polymer other than polydextrose being at least 20% by weight, relative to the total weight of said pharmaceutically acceptable polymer matrix.
2. The pharmaceutical composition as claimed in claim 1, wherein said polydextrose is selected from the group consisting of pharmaceutically acceptable polydextroses having a molecular weight of at most 22 000 g/mol, and blends thereof.
3. The pharmaceutical composition as claimed in claim 1 or 2, wherein said at least one polymer other than polydextrose is selected from the group consisting of cellulose-based polymers, vinyl homo- and copolymers, acrylic and methacrylic polymers, chemically modified starches, pectins, chitin derivatives, gum tragacanth, gelatin, sodium alginate, pullulan, gum arabic, guar gum, agar-agar, xanthan gum, polyalkylene oxides, and blends thereof.
4. The pharmaceutical composition as claimed in claim 3, wherein said at least one polymer other than polydextrose is selected from the group consisting of methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose, weakly substituted hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, carboxymethylethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate, povidone, copovidone, polyvinyl alcohol, acrylic and methacrylic polymers, starches derived from starches extracted from maize, from potato, from rice, from wheat or from tapioca, pectins, chitosan, gum tragacanth, gelatin, sodium alginate, pullulan, gum arabic, guar gum, agar-agar, xanthan gum, polyethylene oxides, polypropylene oxides, copolymers of ethylene oxide and of propylene oxide, and blends thereof.
5. The pharmaceutical composition as claimed in claim 1, wherein said at least one polymer other than polydextrose is selected from the group consisting of hydrophilic polymers other than polydextrose, and blends thereof.


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6. The pharmaceutical composition as claimed in claim 6, wherein said hydrophilic polymers are selected from the group consisting of hydroxypropylcellulose, hydroxyethylcellulose, cationic copolymers of dimethylaminoethyl methacrylates and of neutral methacrylic esters, anionic copolymers of methacrylic acid and of methacrylic acid esters, hydroxypropylmethylcellulose acetate succinate, polyethylene glycols, copovidone, and blends thereof.
7. The pharmaceutical composition as claimed in any preceding claim wherein said at least one polymer other than polydextrose is in the form of a continuous phase of a solid solution of polydextrose in said at least one polymer other than polydextrose.
8. The pharmaceutical composition as claimed in any preceding claim wherein the proportion of said polydextrose is between approximately 20% and approximately 80% by weight, and in that the proportion of said at least one polymer other than polydextrose is between approximately 20% and approximately 80% by weight, relative to the total weight of the pharmaceutically acceptable polymer matrix.
9. The pharmaceutical composition as claimed in claim 1, wherein the weight ratio of said polydextrose to said at least one polymer other than polydextrose, in said polymer matrix, is between approximately 20:80 and approximately 50:50.
10. A method for the production, by extrusion or injection molding, of a pharmaceutical composition as claimed in any preceding claim which comprises adding Amodiarone, said polydextrose and said at least one polymer other than polydextrose, in a mixer and at a mixing temperature of between approximately 50 °C and approximately 250 °C.



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ABSTRACT
A PHARMACEUTICAL COMPOSITION COMPRISING A SOLID DISPERSION COMPRISING AMODIARONE AND . A PHARMACEUTICALLY ACCEPTABLE POLYMER MATRIX
Novel pharmaceutical dosage forms providing for therapeutic amount of a pharmaceutically acceptable salt of Amiodarone are disclosed. The Amiodarone tablet is provided in a pharmaceutically acceptable polymer matrix comprising at least one continuous polydextrose phase and at least one continuous phase of a polymer other than polydextrose The dosage forms are in the form of tablets and such dosage forms have the benefit of overcoming the problem with delivery of Amiodarone which is normally formulated as a parenteral formulation.