DE10353832A1 - Solid pharmaceutical composition containing tropane type inhibitor of neurotransmitter reuptake, useful for treating central nervous system disorders - Google Patents

Abstract

The invention relates to a solid pharmaceutical preparation containing one or more solid carriers and / or excipients and an active ingredient from the group of monoamine neurotransmitter re-uptake inhibitors which have a 2,3-disubstituted tropane skeleton, their preparation and use for Preparation of a medicament for the treatment or prevention of central nervous disorders or disorders.

Description

BACKGROUND OF THE INVENTION

1. TECHNICAL AREA

The The invention relates to a solid pharmaceutical preparation containing one or more solid carrier and / or auxiliaries and an active ingredient from the group of the monoamine Neurotransmitter re-uptake inhibitors with a 2,3-disubstituted Tropan scaffolding, their preparation and use for the manufacture of a medicament for treatment or prevention central nervous system Diseases or disorders.

2. State of the art

monoamine Neurotransmitters re-uptake inhibitors, which are a 2,3-disubstituted Tropan scaffolding are compounds with pharmacologically valuable properties. You can for example, in the treatment of central nervous disorders as with dementia associated with Alzheimer's disease or Parkinson's disease Disease have a high therapeutic benefit.

Such Compounds are known, e.g. from the International Patent Applications WO 93/09814 and WO 97/30997, in which also various administration forms for such Connections are proposed.

On The reason for the very high potency of these compounds is a need for dosage forms with high stability and a low content of active ingredient. Such dosage forms cease Because of the low drug loading high demands on the Manufacturing process in terms of salary uniformity. The required high content uniformity is with conventional manufacturing processes like direct tabletting or wet granulation only difficult to achieve.

Of the The present invention was therefore the object of a solid pharmaceutical dosage form for monoamine neurotransmitters Re-uptake inhibitors which have a 2,3-disubstituted tropane skeleton, with high stability, faster in-vitro dissolution and good bioavailability as well as high content uniformity to disposal to deliver.

It was now surprisingly found that the disadvantages of conventionally prepared dosage forms, particular with regard to the content uniformity can be if you have a solution a drug from the group of monoamine neurotransmitters re-uptake Inhibitors which have a 2,3-disubstituted tropane skeleton, on a carrier spraying and / or the dosage form or the spray medium is a wet binder contains.

SHORT SUMMARY THE INVENTION

• (a) durch Aufsprühen einer Lösung des Wirkstoffs auf mindestens einen Trägerstoff erhältlich ist; und/oder
• (b) mindestens ein Feuchtbindemittel, bevorzugt in der Sprühlösung, enthält.

The invention thus relates to a solid pharmaceutical preparation containing one or more solid carriers and / or adjuvants and an active ingredient from the group of monoamine neurotransmitter re-uptake inhibitors with a 2,3-disubstituted tropane skeleton, which

• (A) is obtainable by spraying a solution of the active ingredient on at least one carrier; and or
• (B) at least one wet binder, preferably in the spray solution contains.

• (a) einen Wirkstoff aus der Gruppe der Monoamin Neurotransmitter Re-uptake Inhibitoren, welcher ein 2,3-disubstituiertes Tropan Gerüst aufweist, in einem geeigneten Lösungsmittel gegebenenfalls in Gegenwart eines Hilfsstoffes löst;
• (b) die erhaltene Lösung auf einen oder mehrere feste Trägerstoffe aufsprüht;
• (c) gegebenenfalls weitere Träger- und Hilfsstoffe zusetzt;
• (d) das erhaltene Gemisch formt und gegebenenfalls presst; und
• (e) gegebenenfalls einem geeigneten Filmüberzug aufbringt.

Another object of the invention is a process for the preparation of such pharmaceutical formulations, wherein

• (A) an active ingredient selected from the group of monoamine neurotransmitter re-uptake inhibitors, which has a 2,3-disubstituted tropane skeleton, in a suitable solvent, optionally in the presence of an excipient dissolves;
• (b) spraying the resulting solution onto one or more solid carriers;
• (c) optionally adding further excipients and auxiliaries;
• (d) shaping and optionally pressing the resulting mixture; and
• (e) optionally applying a suitable film coating.

Finally, the invention relates to the use of a pharmaceutical preparation according to any one of claims 1 to for the manufacture of a medicament for the treatment or prevention of central nervous Erkran depression or disorders selected from the group consisting of depression, any form of dementia, Parkinson's disease or obesity.

BRIEF DESCRIPTION OF THE DRAWINGS

1 describes the dissolution behavior of a pharmaceutical preparation according to the invention in the form of a film tablet with and without wet binder containing 1 mg of a compound of the formula IA at a pH of 1.2.

2 describes the dissolution behavior of a pharmaceutical preparation according to the invention in the form of a film tablet with and without wet binder containing 1 mg of a compound of the formula IA at a pH of 6.8.

DETAILED DESCRIPTION OF THE INVENTION

In Usually the monoamine neurotransmitters are re-uptake Inhibitors with a 2,3-disubstituted tropane skeleton to such as described in International Patent Applications WO 93/09814 and WO 97/30997 are disclosed.

worin
R¹ für ein Wasserstoffatom oder eine C_1-6 Alkylgruppe, insbesondere Wasserstoff, Methyl oder Ethyl steht;
R² für ein Halogenatom oder a eine CF₃ oder Cyanogruppe, insbesondere Fluor, Chlor oder Brom steht;
R³ für ein Wasserstoffatom oder eine C_1-6 Alkylgruppe oder C_3-6-Cycloalkyl-C_1-3-alkylgruppe, insbesondere Methyl, Ethyl oder Propyl steht; und
m 0 oder eine ganze Zahl von 1 bis 3, insbesondere 1 oder 2 ist;
oder ein Tautomer, ein pharmazeutisch akzeptables Salz, Solvat, oder ein physiologisches funktionelles Derivat davon.Preference is given to the compounds of the formula I,

wherein
R ^{1 represents} a hydrogen atom or a C _1-6 alkyl group, in particular hydrogen, methyl or ethyl;
R ^{2 is} a halogen atom or a is a CF ₃ or cyano group, in particular fluorine, chlorine or bromine;
R ^{3 is} a hydrogen atom or a C _1-6 alkyl group or C _3-6 cycloalkyl C _1-3 alkyl group, especially methyl, ethyl or propyl; and
m is 0 or an integer from 1 to 3, especially 1 or 2;
or a tautomer, a pharmaceutically acceptable salt, solvate, or a physiologically functional derivative thereof.

The term "C _1-6 alkyl" as used above and below includes methyl and ethyl groups, as well as straight-chain and branched propyl, butyl, pentyl and hexyl groups. Particularly preferred alkyl groups are methyl, ethyl, n-propyl, isopropyl and t-butyl.

The term "C _3-6 cycloalkyl" as used above and below includes cyclic propyl, butyl, pentyl and hexyl groups such as cyclopropyl and cyclohexyl.

Of the Term "halogen" as he before and includes fluorine, chlorine, bromine and Iodine, of which fluorine and chlorine are particularly preferred.

Of the Term "physiological functional derivative "like It is used above and below includes derivatives which of the compounds of formula (I) under physiological conditions can be obtained, such as N-oxides.

Of the Term "pharmaceutical acceptable acid addition salts "like him and used hereinafter includes acid addition salts formed be with hydrochloric acid, bromic, Sulfuric acid, Phosphoric acid, methanesulphonic, Acetic acid, fumaric acid, succinic acid, Lactic acid, Citric acid, Tartaric acid and maleic acid, the salts of hydrochloric acid, bromic, Sulfuric acid, Phosphoric acid, acetic acid and citric acid are particularly preferred. Most preferably, the salt is the Citric acid.

oder ein pharmazeutisch akzeptables Salz, insbesondere das Citrat davon.Most preferred is the compound of formula IA

or a pharmaceutically acceptable salt, especially the citrate thereof.

Prefers contains the pharmaceutical invention Form of preparation up to 5.00 wt .-%, preferably 0.01 to 3.00 Wt .-%, in particular 0.10 to 1.50 wt .-%, most preferably 0.20 to 0.80 wt .-% of an active ingredient from the group of monoamine neurotransmitters Having re-uptake inhibitors with a 2,3-disubstituted tropane skeleton, where the percentages are based on the particular salt of this active ingredient Respectively.

Farther Preferably, a pharmaceutical preparation is obtainable by spray on a solution of the active ingredient, the solvent Water, an alcohol and optionally a wet binder. The relationship the solvent Alcohol and water may be 100: 0 to 0: 100 (wt%), preferably 20:80 to 80:20 (wt%), more preferably 40:60 to 60:40 (wt%).

preferred Moisture binders are polyvinylpyrrolidione (povidone), copolymers of vinylpyrrolidone with other vinyl derivatives (Copovidone), cellulose derivatives such as methylhydroxypropylcellulose, methylcellulose or hydroxypropylcellulose, in particular hydroxypropylcellulose (HPC).

In a further preferred embodiment precipitated the active ingredient during spraying in predominantly crystalline form on the substrate.

in the In the context of the present invention, carbohydrates such as Lactose or mannose, in particular finely divided lactose and lactose Monohydrate, but also or sugar alcohols such as mannitol, sorbitol or xylitol, especially mannitol as support materials a special Meaning too. These carriers have in the formulation according to the invention proved to be particularly advantageous. A preferred aspect of the present invention The invention therefore relates to an at least one compound of the formula I containing preparation form, in addition to the active ingredient lactose, especially finely divided lactose and lactose monohydrate as a carrier contains.

According to the invention the weight ratio between the components contained in the tablet lactose too the active ingredient in a range of about 200: 1 to about 20: 1. Preferably is the ratio of Lactose to the active ingredient in a range of about 150: 1 to about 50: 1st The proportion by weight of lactose is preferably based on the total mass of the tablet according to the invention in one area from about 50-80 % By weight, preferably between about 55-75% by weight.

Farther preferred are pharmaceutical formulations, wherein the carrier materials selected are from the group consisting of carbohydrates and dry binders.

The term "dry binder" above and below refers to those auxiliaries which are suitable for binding other components together with one another. Binders preferred according to the invention are selected from the group consisting of:
Powdered cellulose, microcrystalline cellulose, sorbitol, starch, polyvinylpyrrolidone (povidone), copolymers of vinylpyrrolidone with other vinyl derivatives (copovidones), cellulose derivatives, especially methylhydroxypropylcellulose, eg Methocel E 5 P, and mixtures of these compounds. Powder cellulose, especially microcrystalline cellulose and / or copovidone, are preferably present as binders. Most preferred is microcrystalline cellulose.

by virtue of this particularly preferred carrier combination from microcrystalline cellulose, anhydrous lactose and lactose Monohydrate will be tablets with high mechanical stability and at the same time rapid release of active substance and thus good bioavailability receive.

If one of the abovementioned binders is added to the formulation according to the invention, then For example, the weight ratio of lactose to binder is preferably about 5: 1 to about 1: 2, preferably about 3: 1 to about 1: 1, more preferably about 2.5: 1 to 1.5: 1.

Farther preferred are pharmaceutical preparation forms, wherein the excipients selected are from the group consisting of wet binders, lubricants, Disintegrators, release agents and wetting agents.

in the Within the scope of the present invention, these disintegrants may optionally also be referred to as a disintegrant. These are preferred according to the invention selected from the group consisting of sodium starch glycolate, cross-linked Polyvinyl pyrrolidones (crospovidone), croscarmellose sodium salt (cellulose carboxymethylether sodium salt, cross-linked), carboxymethylcellulose, dried corn starch and mixtures thereof. Particularly preferred are within the scope of the present invention Invention sodium starch glycolate, Crospovidone and, preferably, croscarmellose sodium salt for use. If the above-mentioned disintegrants are used, their proportion by weight lies based on the total mass of the tablet according to the invention preferably in one Range of about 0.5-10 % By weight, more preferably about 1.0-5.0% by weight.

When Lubricants come within the scope of the present invention, for example silica, talc, stearic acid, sodium stearyl fumarate, Magnesium stearate and glycerol tribehenate. According to the invention preferred Vegetable magnesium stearate is used. Become prominent called flow or Flow regulators or lubricant used, their weight fraction based on the total mass of the dosage form according to the invention is preferred in a range of about 0.1-10 % By weight, preferably about 0.5-5 % By weight, more preferably between 0.6 and 1.0% by weight.

In a preferred embodiment is the formulation of the invention a tablet, in particular a film-coated tablet.

In usually there is the film coating essentially one or more film formers, one or more several means to increase the elasticity, the so-called plasticizers, one or more release agents, one or more pigments and optionally one or more Dyes.

• – 35 bis 65 Gew.-% mindestens eines Filmbildners, insbesondere HPMC;
• – 3,5 bis 10% Gew.-% mindestens eines Mittels zur Erhöhung der Elastizität, insbesondere PEG;
• – 5 bis 20 Gew.-% mindestens eines Coatings, insbesondere eines Silikates;
• – 10 bis 40 Gew.-% mindestens eines Pigmentes, insbesondere Titandioxid
• – 0 bis 10% Gew.-% mindestens eines Farbstoffes, insbesondere von Eisenoxiden.

bezogen auf die Gesamtmasse des Filmüberzuges.Preferred is a film-coated tablet, wherein the film coating consists essentially of

• From 35 to 65% by weight of at least one film former, in particular HPMC;
• From 3.5% to 10% by weight of at least one elasticity-enhancing agent, in particular PEG;
• - 5 to 20 wt .-% of at least one coating, in particular a silicate;
• - 10 to 40 wt .-% of at least one pigment, in particular titanium dioxide
• 0 to 10% by weight of at least one dyestuff, in particular of iron oxides.

based on the total mass of the film coating.

• (i) einem Wirkstoff aus der Gruppe der Monoamin Neurotransmitter Re-uptake Inhibitoren, welcher ein 2,3-disubstituiertes Tropan Gerüst aufweisen, vorzugsweise einer Verbindung der Formel (I), insbesondere die Verbindung der Formel (IA);
• (ii) einem oder mehreren Trägermaterialien ausgewählt aus der Gruppe bestehend aus Kohlenhydraten und Trockenbindemitteln, vorzugsweise Laktose und Cellulose;
• (iii) einem oder mehreren Hilfsstoffe ausgewählt aus der Gruppe bestehend aus Cellulose-Derivaten und Salzen von Fettsäuren, vorzugsweise HMC, CMC Na, quervernetzt, und Magnesiumstearat;
• (iv) einem Filmüberzug, der im wesentlichen aus einem oder mehreren Filmbildnern, einem oder mehreren Mitteln zur Erhöhung der Elastizität, einem oder mehreren Trennmitteln, einem oder mehreren Pigmenten und gegebenenfalls einem oder mehreren Farbstoffen besteht.

Preferred is a pharmaceutical preparation according to one of the preceding claims, characterized in that it consists essentially of the following components:

• (I) an active ingredient from the group of monoamine neurotransmitter re-uptake inhibitors, which have a 2,3-disubstituted tropane skeleton, preferably a compound of formula (I), in particular the compound of formula (IA);
• (ii) one or more carrier materials selected from the group consisting of carbohydrates and dry binders, preferably lactose and cellulose;
• (iii) one or more adjuvants selected from the group consisting of cellulose derivatives and salts of fatty acids, preferably HMC, CMC Na, cross-linked, and magnesium stearate;
• (iv) a film coating consisting essentially of one or more film formers, one or more elasticity enhancing agents, one or more release agents, one or more pigments, and optionally one or more colorants.

• (i) 0,01 bis 5,00 Gew.-% eines Wirkstoffs aus der Gruppe der Monoamin Neurotransmitter Re-uptake Inhibitoren, welcher ein 2,3-disubstituiertes Tropan Gerüst aufweisen, insbesondere 0,02 bis 3,00 Gew.-% eines Wirkstoffs der Formel I;
• (ii) 80,00 bis 95,00 Gew.-% eines oder mehrerer Trägermaterialien ausgewählt aus der Gruppe bestehend aus Kohlenhydraten und Trockenbindemitteln, insbesondere Trägermaterialien bestehend aus: a. 27,5 bis 32,5 Gew.-% wasserfreier Lactose; b. 27,5 bis 32,5 Gew.-% Lactose Monohydrat; c. 25,0 bis 30,0 Gew.-% mikrokristalliner Cellulose;
• (iii) 1,00 bis 10,00 Gew.-% eines oder mehrerer Hilfsstoffe ausgewählt aus der Gruppe bestehend aus Cellulose-Derivaten und Salzen von Fettsäuren, insbesondere 2,00 bis 8,00 Gew.-% eines oder mehrerer Hilfsstoffe ausgewählt aus der Gruppe bestehend aus HPC, CMC Na, quervernetzt, und Magnesiumstearat;
• (iv) 0 bis 10,00 Gew.-% eines Filmüberzuges, der im wesentlichen aus einem oder mehreren Filmbildnern, einem oder mehreren Plastifizierungsmittel, einem 1,00 bis 5,00 Gew.-% eines Filmüberzuges umfassend HPMC, MHPC, PEG, ein oder mehrere Silikate, Titandioxid und ein oder mehrere Eisenoxide oder mehreren Pigmenten und gegebenenfalls einem oder mehreren Farbstoffen besteht, insbesondere 1,00 bis 5,00 eines Filmüberzuges umfassend HPMC, MHPC, PEG, ein oder mehrere Silikate, Titandioxid und ein oder mehrere Eisenoxide.

Particularly preferred is a pharmaceutical preparation in the form of a film-coated tablet consisting essentially of the following components:

• (i) 0.01 to 5.00% by weight of an active substance from the group of the monoamine neurotransmitter re-uptake inhibitors which have a 2,3-disubstituted tropane skeleton, in particular 0.02 to 3.00% by weight an active ingredient of the formula I;
• (Ii) 80.00 to 95.00 wt .-% of one or more carrier materials selected from the group consisting of carbohydrates and dry binders, in particular carrier materials consisting of: a. 27.5 to 32.5% by weight of anhydrous lactose; b. 27.5 to 32.5% by weight of lactose monohydrate; c. 25.0 to 30.0% by weight of microcrystalline cellulose;
• (Iii) 1.00 to 10.00 wt .-% of one or more excipients selected from the group consisting of cellulose derivatives and salts of fatty acids, in particular 2.00 to 8.00 wt .-% of one or more excipients selected from the group consisting of HPC, CMC Na, cross-linked, and magnesium stearate;
• (iv) 0 to 10.00% by weight of a film coat consisting essentially of one or more film formers, one or more plasticizers, 1.00 to 5.00% by weight of a film coat comprising HPMC, MHPC, PEG, one or more silicates, titanium dioxide and one or more iron oxides or more pigments and optionally one or more dyes, in particular 1.00 to 5.00 of a film coating comprising HPMC, MHPC, PEG, one or more silicates, titanium dioxide and one or more iron oxides ,

to Preparation of the preparation according to the invention the active ingredient is in a solvent optionally dissolved in the presence of a wet binder, on the carriers, especially finely divided, anhydrous lactose, lactose monohydrate and microcrystalline cellulose as binder, mixed, sieved and subsequently dried. The product obtained is optionally decomposed, in particular CMC Na, cross-linked, with the flow agent, in particular magnesium stearate mixed. The resulting mixture is then placed on a suitable tablet press to the tablets according to the invention pressed.

The Pressing forces, which needed be tablets of suitable breaking strength and thus the desired Decay times are dependent on the shapes and sizes used stamping tools. Preferably, pressing force in a range of 2-20 kN, especially from 5-15 kN. Higher press forces can too Tablets with slower drug release lead. lower Press forces can lead to mechanically unstable tablets. The tablet cores can be different Have formats, preferably round are large-domed or biconvex and oval or oblong forms.

Subsequently, will a solution of the film former and plasticizer made in water that insoluble in it Release agents and pigments dispersed and the resulting suspension applied to the tablets.

The The following examples serve to illustrate formulations according to the invention. They are just as possible, To understand exemplary procedures illustrated without the Restrict the invention to its content.

example 1

It are film-coated tablets made up of:

I. COMPOSITION

II. PRODUCT DESCRIPTION

III. PREPARATION A) Tablets

Process data:

• Nozzle head: 1.1 mm spray pressure: approximately 2 bar Rotation: 100 ° (during drying and cooling)

During the Drying and cooling should the mixer run on interval switching, i. Mix for 1 minute, then 2 minutes rest.

3. Dry sieving

Prozessdaten: Freifallmischer: Servolift Kubus 601 Mischgeschwindigkeit: 10 UpM Anzahl der Umdrehungen: 100 U (Ac-Di-Sol INT) 30 U ( MgSt.INT ) 5. Tabletten

Prozessdaten: Tablettenpresse: Korsch EKO Werkzeug: 9 mm WR 13,5, bigewölbt mit Facette + BI-Logo Pressgeschwindigkeit Stufe 4 Presskraft: ca. 11–12 kN Using a suitable sieving machine, shred the dried granules. Process data: screening machine: Comil 197 p Screen size: RS 2007 Spacer ring: DR 125 4. final mixture

Process data: Tumbler: Servolift Kubus 601 Mixing speed: 10 rpm Number of revolutions: 100 U (Ac-Di-Sol INT) 30 U (MgSt.INT) 5. Tablets

Process data: Tablet press: Korsch EKO Tool: 9 mm WR 13.5, big vaulted with facet + BI logo pressing speed Level 4 Pressing power: about 11-12 kN

B) film-coated tablets

6. coating suspension / solution

7. coating suspension / dispersion

8. coating suspension

9. filming

Example 2

Analogous Example 1, corresponding uncoated tablets are prepared, being a solution of Active substance of the formula (IA) in the form of the citrate dissolved in water and ethanol but without the addition of hydroxypropyl cellulose on the support material is applied.

Example 3 Investigation the dissolution rate

The Tablets according to the examples 1 and 2 are each taken in 900 ml of a simulated gastric fluid from pH 1.2 or a simulated intestinal flora of pH 6.8 (0.05 M phosphate buffer) at a stirring speed of 50 upm or 75 upm solved. The content of dissolved Compound of formula (IA) is determined by HPLC.

The temporal course of this resolution can the 1 and 2 be removed.

Beispiel 1 mit Feuchtbindemittel

Beispiel 2 ohne FeuchtbindemittelWhere:

Example 1 with wet binder

Example 2 without wet binder

Claims (21)

Solid pharmaceutical preparation containing one or more solid carrier and / or auxiliaries and an active ingredient from the group of the monoamine Neurotransmitters re-uptake inhibitors, which are a 2,3-disubstituted Tropan scaffolding have, available by spraying a solution of this active ingredient on at least one carrier. Solid pharmaceutical preparation containing one or more solid carrier and / or auxiliaries and an active ingredient from the group of the monoamine Neurotransmitters re-uptake inhibitors, which are a 2,3-disubstituted Tropan scaffolding have, characterized in that they at least one wet binder contains. Pharmaceutical preparation according to claim 1 or 2, characterized in that the active substance is a compound of the formula I.

wherein R ^{1 represents} a hydrogen atom or a C _1-6 alkyl group; R ^{1 represents} a halogen atom or a represents a CF ₃ or cyano group; R ^{3 represents} a hydrogen atom or a C _1-6 alkyl group or C _3-6 cycloalkyl C _1-3 alkyl group; and m is 0 or an integer from 1 to 3; or a tautomer, a pharmaceutically acceptable salt, solvate, or a physiological functional derivative thereof. Pharmaceutical preparation according to one of the preceding claims, characterized net, that the active ingredient is a compound of the formula IA

or a pharmaceutically acceptable salt thereof. Pharmaceutical preparation according to one of the preceding claims available by spraying a solution of the active ingredient, the solvent Water, an alcohol and optionally a wet binder. Pharmaceutical preparation according to one of the preceding Claims, characterized in that the wet binder hydroxypropyl cellulose (HPC) is. Pharmaceutical preparation according to one of the preceding Claims, characterized in that the active ingredient during spraying in predominantly crystalline form on the substrate precipitated. Pharmaceutical preparation according to one of the preceding Claims, characterized in that the carrier materials are selected from the group consisting of carbohydrates and dry binders. Pharmaceutical preparation according to one of the preceding Claims, characterized in that the carrier materials substantially consist of lactose and cellulose. Pharmaceutical preparation form according to one of previous claims, characterized in that the carrier materials substantially consist of anhydrous lactose, lactose monohydrate and microcrystalline Cellulose. Pharmaceutical preparation form according to one of previous claims, characterized in that the auxiliaries are selected selected from the group consisting of wet binders, lubricants, disintegrants, Release agent and wetting agent. Pharmaceutical preparation form according to one of previous claims, characterized in that the excipients substantially Cellulose derivatives and salts of fatty acids consist. Pharmaceutical preparation form according to one of previous claims, characterized in that the excipients substantially Hydroxypropylcellulose (HPC), carboxymethylcellulose Na, cross-linked (Croscarmellose) and magnesium stearate exist. Pharmaceutical preparation form according to one of previous claims, characterized in that it is a film-coated tablet. Pharmaceutical preparation according to claim 13, characterized in that the film coating substantially from one or more film formers, one or more means for increase the elasticity, one or more release agents, one or more pigments and optionally one or more dyes. Pharmaceutical preparation according to claim 13 or 14, characterized in that the film coating hydroxypropylmethylcellulose (HPMC), methylhydroxypropylcellulose (MHPC), polyethylene glycol (PEG), one or more silicates, titanium dioxide, and one or more iron oxides contains. Pharmaceutical preparation according to one of the preceding claims, characterized in that it consists essentially of the following components: (i) an active agent selected from the group consisting of monoamine neurotransmitter re-uptake inhibitors which have a 2,3-disubstituted tropane skeleton; (ii) one or more carrier materials selected from the group consisting of carbohydrates and Dry binders; (iii) one or more adjuvants selected from the group consisting of cellulose derivatives and salts of fatty acids; (iv) a film coating consisting essentially of one or more film formers, one or more elasticity enhancing agents, one or more pigments and optionally one or more colorants. Pharmaceutical preparation form according to one of previous claims, characterized in that it consists essentially of the following components consists: (I) 0.01 to 5.00 wt .-% of an active ingredient from the Group of monoamine neurotransmitters re-uptake inhibitors, which a 2,3-disubstituted tropane skeleton; (ii) 80.00 to 95.00 wt .-% of one or more support materials selected from the group consisting of carbohydrates and dry binders; (Iii) 1.00 to 10.00 wt .-% of one or more excipients selected from the group consisting of cellulose derivatives and salts of fatty acids; (Iv) 0 to 10.00% by weight of a film coating, consisting essentially of one or more film formers, one or more means to increase the elasticity, one or more pigments and optionally one or more Dyes exists. Pharmaceutical preparation form according to one of previous claims, characterized in that it consists essentially of the following components consists: (i) 0.02 to 3.00% by weight of an active ingredient of the formula I; (ii) a carrier material consisting of: d. 27.5 to 32.5% by weight of anhydrous lactose; e. 27.5 to 32.5% by weight of lactose monohydrate; f. 25.0 to 30.0% by weight microcrystalline cellulose; (iii) 2.00 to 8.00% by weight of one or more excipients selected from the group consisting of HPC, CMC and magnesium stearate; (Iv) 1.00 to 5.00 of a film coating comprising HPMC, PEG, one or more silicates, titanium dioxide and one or more iron oxides. Process for the preparation of a pharmaceutical Preparation form according to one of claims 1 to 19, characterized that he (a) an active substance from the group of monoamine neurotransmitters Re-uptake inhibitors having a 2,3-disubstituted tropane skeleton, in a suitable solvent optionally in the presence of an adjuvant dissolves; (b) the obtained solution on one or more solid carriers sprays; (C) if necessary, further carrier and adjuncts; (d) shaping the resulting mixture and if necessary, presses; and (e) if appropriate, a suitable one film coating applies. Use of a pharmaceutical preparation according to one of the claims 1 to 19 for the manufacture of a medicament for the treatment or Prevention of Central Nervous Diseases or disorders selected from the group consisting of depression, any form of dementia, Parkinson's disease or obesity.