DE10256775A1 - Preparation of film forming composition for transmucosal delivery of nicotine used for treating tobacco addiction, includes converting nicotine free base to its salt with acid and/or incorporation of nicotine as salt - Google Patents

Abstract

Preparation of a film-forming composition (A) for transmucosal delivery of nicotine (I) includes converting (I) free base to its salt (Ia) with an acid (II) and/or incorporation of (I) as (Ia). (Ia) are formed from fruits acids, especially citric, tartaric, malic, succinic or fumaric acid, or acetic, lactic, ascorbic, adipic or phosphoric acids. An Independent claim is also included for a film-forming composition for transmucosal delivery of (I), prepared as above or containing at least one layer in which (I) is present as a salt with the specified acids.

Description

The present invention relates film-shaped Preparations for the transmucosal administration of nicotine. This Preparations are particularly suitable for use in smoking weaning or nicotine substitution. The invention includes Furthermore, methods with which such preparations advantageous to Way can be made.

Nicotinic drug administration has been used successfully for several years for smoking cessation or for the treatment of nicotine dependence. For the administration of nicotine, nicotine patches, nicotine chewing gums, sublingual tablets or nicotine sprays are used in particular. The transbuccal administration is particularly advantageous from a galenical point of view, because absorption through the oral mucosa allows rapid onset of action and optimal utilization of the active substance. US Pat. No. 6,183,775 B1 describes lozenges or lozenges for the buccal administration of drugs, for example nicotine in the form of nicotine tartrate.

Basically, for administration Nicotine is only suitable for those forms of administration which have a sufficient stability and which are capable of controlling the active ingredient To give way. Particular problems arise from the fact that nicotine a very volatile one Substance is.

A novel dosage form for the buccal or transmucosal administration provide drug-containing film-like systems These can as adhesive Films are formed in aqueous or physiological media (eg, saliva) during the period of application either completely disintegrate or not or only partially disintegrate. The drug release takes place predominantly by diffusion, possibly supported by the disintegration of the film. After oral administration of such a film-shaped dosage form the drug is released in the oral cavity and subsequently on the Mouth mucosa resorbed. However, there is the possibility the existence Part of the released drug is swallowed, causing the for the transmucosal or transbuccal absorption reduced available dose is. To avoid this disadvantage and to a possible quick use of the desired To achieve an effect is a rapid transmucosal uptake of the Active ingredient required.

US 4,855,142 describes a mucoadhesive patch consisting of a film-shaped, water-insoluble cover layer and a mucoadhesive, water-insoluble layer which is optionally active ingredient-containing. As active ingredient, nicotine is considered.

Furthermore, it is off US Pat. No. 6,319,510 B1 a dosage form known which is applied to the gums. This dosage form has a complicated multi-layered construction comprising at least three layers. The active substance is located in the middle layer, which serves as a reservoir layer. The reservoir layer is provided on one side with a mucoadhesive, impermeable layer and on the other side with a semipermeable membrane. The drug delivery takes place in such a way that water or saliva passes through the membrane into the reservoir layer, whereby the active ingredient is dissolved and diffused through the membrane to the outside.

US Pat. No. 6,284,264 B1 describes a method for the release of drugs in the oral cavity using an active ingredient-containing water-soluble mucoadhesive film. Nicotine salicylate is suggested as the active ingredient.

Planiform, decomposing in aqueous environment Dosage forms, especially oral dosage forms containing a rapid release of active ingredients in the oral cavity or in other body orifices or body cavities enable, are already known and are often referred to as "wafers". Because of their low Layer thickness and disintegration or resolvability own these film-shaped, flat dosage forms, especially for rapid release of medications and other active ingredients in the mouth.

Nicotine-containing medicines, z. B. film-shaped Preparations are basically difficult to produce because nicotine is very volatile and also toxic. In the processing of nicotine in particular the problem occurs on that at Evaporation of the solvents used in the preparation a considerable Share of volatile Nicotine can evaporate, this being because of the volatility and toxicity of nicotine is highly undesirable. In particular, the drying process poses a risk potential In addition, nicotine mostly used in excess must become, to get medicines with a sufficient nicotine dose.

Because of these characteristics of the Nicotins are additional activities required in the production to reduce environmental impact and a health hazard of the staff.

The underlying of the invention The task was to demonstrate pharmaceutical preparations, which the delivery of nicotine to mucous membranes, in particular to the oral mucosa, allow, and which can be produced by a process which is the abovementioned Disadvantages avoids. Furthermore, an improved control the time course of drug release are enabled.

Furthermore, the object was to Manufacturing process for to show the said nicotine-containing preparations, by which by the volatility nicotine-related problems can be avoided.

These tasks are solved by the manufacturing method according to claim 1 and those in the dependent claims described embodiments, as well as through film-shaped Preparations according to the claims 11, 12 and 13 and the following subclaims.

The process according to the invention for the preparation nicotine-containing film Preparations are characterized by at least one process step, in which the nicotine base by reaction with an acid is converted into a salt, and / or by a step in which nicotine is added in salt form. In the latter case, it is nicotine salt (s) from the the following group: acid salts, in particular salts of citric acid, tartaric acid, malic acid, succinic acid, fumaric acid; such as Salts of acetic acid, Lactic acid, ascorbic acid, adipic acid and phosphoric acid. Particular preference is given to using the fruit-acidic salts of nicotine, such as B. nicotine tartrate, citrate, malate, fumarate.

Preferably, the manufacturing process done in the way that the the total amount of nicotine used is converted into a nicotine salt, or that nicotine exclusively in the form of a nicotine salt as indicated, used and incorporated becomes.

These measures will ensure that that at the production no or only minimal drug losses auftre th and by the volatility the nicotine-related disadvantages are avoided.

The preparation of the film-shaped preparations according to the invention is generally carried out in such a way that first a coating composition prepared and this is spread on an inert pad to a wet film. This is subsequently dried and, if necessary, divided into dosage units of the desired area size. Preferably, the dried film is divided into area sections whose size is less than 10 cm ² , preferably less than 8 cm ² , more preferably less than 4 cm ² .

The inventive measures can be beyond also use in manufacturing processes that on another Principle based.

The coating composition generally becomes using water, alcohol or other solvents produced. It contains in addition to the active ingredient nicotine constituents, which are the matrix of Form films (matrix formers), and optionally one or more Ingredients from the group of fillers, dyes, disintegrants (Wicking agent), emulsifiers, sweeteners, Plasticizers, preservatives, flavors, taste-refreshers, Taste maskers and complexing agents. The constituents of the coating composition are in water or a suitable solvent or solvent mixture solved, suspended or dispersed. The selection of suitable solvents depends on the type of formulation ingredients; suitable solvents are known in the art.

This solution, suspension or dispersion is by doctor blade, roller coating, spraying or extrusion process coated on an inert pad and dried, creating a Film layer is formed. Alternatively, it is also possible under Use of suitable formulation ingredients to produce a melt, which contains nicotine in salt form, and this melt in the manner described on a pad coat.

In the preparation of the coating composition is nicotine, as mentioned above, either added in the form of one of said salts, or Nicotine is used as base and salted by adding one or more acids. The nicotine salts used or formed are non-volatile, causing an improvement in the process with increased yield allows becomes.

The dissolved or dissolved in the wafer matrix dispersed drug is present after release in the mouth as a solution or dispersion over and over the mucosa is absorbed directly. In the application of a film-like preparation according to the invention in the oral cavity dissociates the nicotine salt contained in the preparation, thereby Nicotine is released as a base and absorbed through the mucosa can.

In the mentioned method step, in which the free base nicotine by adding at least one Acid in the appropriate salt is transferred, will be used as acid (s) preferably one or more acid (s) which is selected from the group consisting of citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, acetic acid, lactic acid, salicylic acid, ascorbic acid, adipic acid and phosphoric acid includes. The use of fruit acids, such as Tartaric acid, Citric acid, malic acid, succinic acid, fumaric acid especially advantageous, as well as salicylic acid. Most preferred is tartaric acid (L (+) - tartaric acid, D (+) - tartaric acid, meso-tartaric acid, as well as racemic mixtures thereof).

In addition to the acids mentioned come also other organic acids (eg monocarboxylic acids, dicarboxylic acids, polybasic carboxylic acids, aromatic carboxylic acids like benzoic acid) or inorganic acids if they are for the production of medicines are suitable.

The amount of acid (s) used is preferably chosen that one full Salinization of nicotine is achieved. However, the invention includes also such systems, which after completion of the salinization reaction Acid in excess; this is partly for requires the crosslinking of polymeric components, thereby the solution behavior of the system.

According to another embodiment of the method it is provided that the film-like preparation is used as a or multilayer film is produced. This can be, for example done in the way that first a first film layer is prepared (as described above) and on this dried first film layer applied another layer becomes. Alternatively you can made two separate layers in separate process steps and these layers are subsequently laminated together.

The invention comprises on the one hand film-shaped nicotine-containing preparations obtained by the method according to the invention are made, and above also film-shaped Preparations for the transmucosal administration of nicotine, the single or multi-layered, with at least one layer of nicotine contains in salt form. Any / Nicotinine salt (s) is / are selected from the following group: fruit acid Salts, in particular salts of citric acid, tartaric acid, malic acid, succinic acid, fumaric acid; Acetic acid, lactic acid, ascorbic acid, adipic acid and Phosphoric acid. Preferably, the entire is present in the film-shaped preparation Amount of nicotine in salt form. The active substance content (nicotine or Nicotine salt) 0.5 to 50 wt .-%, preferably 1 to 40 wt .-%, particularly preferably 5 to 30 wt .-%, each based on a film-like preparation.

Furthermore, the invention also includes such Embodiments, which an active ingredient combination of nicotine (as a salt, as above described) and at least one further drug.

The film layer, or individual film layers, has / have a solid matrix. Suitable matrix-forming constituents are in particular: polyvinyl alcohols (fully or partially hydrolyzed), cellulose derivatives such as. Hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxypropylethylcellulose (HPEC), hydroxyethylcellulose (HEC), ethylcellulose (EC), propylcellulose, carboxymethylcellulose (CMC) and NaCMC; Mixtures of cellulose ethers; cellulose acetate; Starch and starch derivatives, more preferably tapioca starch; Polyvinyl acetate, polyvinyl pyrrolidones, polyethylene oxide polymers, polyethylene glycols (PEG), polyurethane, polyacrylic acid, polyacrylates, polymethacrylates, poly (methyl vinyl ether-maleic anhydride) (eg., Gantrez ^® grades, such as Gantrez-AN, -S, -ES, -MS , in particular Gantrez ^® AN 119, Gantrez AN 117 and Gantrez ^® MS ^® 955; from ISP). Alginates, pectins, pullulan, gelatins, and natural gums.

The components mentioned can also be used in combination or as mixtures. If the film-like preparation is two- or multi-layered, can the individual layers preferably have a different composition in terms of the matrix-forming constituents, but also with respect to other constituents, respectively.

The matrix-forming polymer (s) represents / constitute an essential part of the film-like preparation; the polymer content is at least 5% by weight and at most 90 wt .-%, preferably 10 to 70 wt .-%, particularly preferably 20 to 50 wt .-%, each based on the total film-like preparation.

The total thickness of a film-shaped preparation ("wafer") can be 5 μm to 5 mm, preferably 30 μm to 2 mm and particularly preferably 50 μm to 1 mm. The wafer may be present as a dense structure, the density between 0.3 g / cm ³ and 1.7 g / cm ³ , preferably between 0.5 g / cm ³ and 1.5 g / cm ³ , particularly preferably between 0 , 7 g / cm ³ and 1.3 g / cm ³ . The surface shape of the individual wafers can advantageously be round, oval, triangular or quadrangular, polygonal or have an arbitrarily rounded shape. Furthermore, the invention also includes such embodiments in which at least one side of the wafer or both sides has a raised structure and / or depressions, for example knobs, ribs or grooves.

The film-like preparations or individual Layers of such a preparation may further comprise auxiliaries or additives included to the chemical or physical properties too influence, such. Flexibility, mucoadhesive properties, disintegration, Swelling capacity, Diffusion properties. By appropriate selection of matrix components and auxiliaries or additives can be achieved that the wafers optionally translucent or opaque (not translucent).

Suitable auxiliaries or additives are, in particular, substances from the following groups:
Fillers such. For example SiO ₂ ; Dyes such as quinoline yellow, TiO ₂ , Brilliant Acid Green;
Disintegrating agents or wicking agents that draw water into the matrix, such. B. Aerosil;
Emulsifiers such as Tween (polyethoxylated sorbitan fatty acid esters), Brij (polyethoxylated fatty alcohols);
Sweeteners such as aspartame, sodium cyclamate, saccharin, sucralose, acesulfame K and their salts;
Plasticizers such as PEG (polyethylene glycol), glycerin, polyurea, sorbitol, mannitol and other sugar alcohols; dexpanthenol;
Polyalcohols such as propanediol, butanediol, glycerin, mygliol; Preservatives such. B. sorbic acid or de salts, vitamins A and E; Flavors such as peppermint, mint, lemon, fruit blends.

Particularly preferred is the additive of substances that act as taste-fresheners, in particular monoterpenes such as Menthol or camphor, as well as the addition of substances that act as a taste masker, such. For example, sodium bicarbonate, Sodium carbonate, potassium bicarbonate, potassium carbonate.

The proportion of these auxiliaries can preferably 0.5 to 30% by weight, in particular 1 to 20% by weight, in each case based on the entire preparation.

According to a particularly preferred embodiment is the active ingredient nicotine or its salt bound as a complex. This causes the film-shaped Preparation, or at least one layer of this preparation, a delayed Having drug release.

For complex formation are particularly suitable Cation exchangers such as Amberlite (eg types IRP 69, IR 120; Rohm and Haas). These are for approved for use in pharmaceutical formulations.

of additional benefit is with this embodiment, that one improved taste masking is achieved, which makes the unpleasant Smell and taste of nicotine is suppressed. This measure can additionally used for the use of said taste maskers and taste refreshers which, by far the suppression of the unpleasant taste and Odor of nicotine can be achieved.

• (i) als nicht mucoadhäsive, in wässrigen Medien schnell zerfallende Filme;
• (ii) als mucoadhäsive Filme, die in wässrigen Medien nicht oder nur teilweise löslich sind;
• (iii) als mucoadhäsive Filme, die in wässrigen Medien löslich oder darin zerfallsfähig oder gelierbar oder quellfähig sind,

ausgeführt sein.The film-shaped nicotine-containing preparations according to the invention can optionally

• (i) as non-mucoadhesive films rapidly disintegrating in aqueous media;
• (ii) as mucoadhesive films that are not or only partially soluble in aqueous media;
• (iii) as mucoadhesive films that are soluble or decayable or gellable or swellable in aqueous media,

be executed.

Under "aqueous Media "in particular Water, watery solutions as well as physiological fluids or body fluids (eg body secretions, Saliva, mucus).

Fast "disintegrating films" are understood to mean those within of 2 min, preferably 60 s, in particular 10 s, completely or essentially complete disintegrated. For the wafers according to (iii) is the Disintegration time preferably 10 seconds to 12 hours, more preferably 1 minute to 1 h, most preferably 3 min to 15 min.

The preparations according to the invention are characterized according to one preferred embodiment in that they the active ingredient nicotine within 20 min, preferably within of 10 minutes, more preferably within 5 minutes after application release.

In any case, the films according to the embodiments (i), (ii) or (iii) are also formed as two- or multi-layer films his.

The mucoadhesive properties as well as the Decay properties are essentially determined by the nature of the matrix-forming polymer / polymers, and the relative proportions of these Polymers determined in the preparation.

As matrix-forming polymers which may be constituents of a mucoadhesive formulation according to the invention, occur - without excluding other suitable raw materials - preferably, the following polymers are: polyvinyl alcohol (for example, Mowiol ^®.); Cellulose derivatives such as hydroxypropylmethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose (such as Walocel ^®.), Methyl cellulose, hydroxyethyl cellulose and hydroxypropyl; Starch and starch derivatives; Gelatin (various types); polyvinylpyrrolidone; Gum arabic; pullulan; Acrylates.

According to another preferred embodiment The invention provides that the nicotine-containing wafer in the form of thin, solidified foams available. This embodiment is especially in the rapidly disintegrating film-like preparations of type (i) preferred. Because of its large inner surface and the relatively stiff design On the one hand, they are characterized by an excellent "mouthfeel", and on the other hand enable a particularly rapid release of active ingredient.

The density of these dry foams is preferably between 0.01 g / cm ³ and 0.9 g / cm ³ , more preferably between 0.08 g / cm ³ and 0.4 g / cm ³ , and most preferably between 0, 1 g / cm ³ and 0.3 g / cm ³ . The volume used for the calculation of the density is defined by the volume filled or enveloped in the entire body of the wafer.

Such foam-like wafers can be obtained as follows: First, a solution or dispersion is prepared which contains the constituents mentioned, in particular matrix polymer (s) and nicotine or nicotine salt. This solution or dispersion, which may also be a concentrated solution or viscous mass, is then foamed by introducing gas or gas mixture (eg air), for example by means of a dispersing unit, but also by other methods, for example by means of ultrasound. In order to stabilize the foams or bubble-containing masses thus produced, a foam-stabilizing agent is added before or during foam generation. Suitable agents for this purpose, for example surfactants, are known to the skilled person. Finally, the bubble-containing mass or foam is spread on a suitable backing as a film or layer and subsequently dried. By solvent removal, the foam solidifies during drying to form an airgel, the resulting cavities receive a permanent structure.

According to further preferred embodiments The invention provides that the film-like preparations are used as or multilayer systems are formed. Such a multi-layered one Structure is particularly in mucoadhesive film-like preparations (i, ii) prefers. These preparations always have a mucoadhesive layer preferably water-soluble or disintegrating is. On the mucoadhesive Layer follows in the distal direction at least one further film-shaped layer.

It is further preferred that the mucoadhesive layer contains the active ingredient. The distal layer (s) may also act as an active agent reservoir be formed so that the Systems formed from these layers are capable of delivering the active ingredient via a Period of preferably up to 24 hours to provide and release more preferably up to 12 hours and most preferably up to 6 h.

To directly after the application To ensure a rapid initial drug delivery may be of use to the measure be made that at least one of the distal layers of a multilayer system as one in aqueous Media soluble or disintegratable Layer is formed. Furthermore, according to another preferred embodiment provided that at least one of the distal layers of a multilayered film-like preparation as one not in watery Media soluble, is formed drug-containing barrier layer, which the Diffusion of active ingredient and / or water slows or prevents.

To carry out a nicotine substitution can the mucoadhesive film-shaped Preparations (type i, ii) on the oral mucosa, in particular being glued to the gum, palate or cheek, taking the active ingredient depending on the embodiment one-sided (ie over the mucoadhesive Layer) or both sides (i.e. the mucoadhesive Layer and additionally over at least one of the distal layer (s)) is delivered.

The mucoadhesive, soluble, disintegratable or gelling wafers (type ii) are also glued to mucous membranes, whereupon these wafers are then exposed by the action of the surrounding liquid (eg saliva) gradually disintegrate, dissolved or form a gel containing the active ingredient contained therein gives off to the tissue.

The dosage forms of the invention are preferably administered orally; about that In addition, the Invention also embodiments, which are suitable for rectal or vaginal use.

The nicotine-containing film-form preparations according to the invention are suitable in an advantageous manner by performing a temporary or permanent nicotine substitution, especially for smoking cessation.

The invention is characterized by the following Formulation examples closer explains:

Example 1:

Non-adhesive, disintegrating, fast releasing film-like Preparation.

Preparation: The solvent is initially charged and the matrix (here: Metolose 60SH50 ^®) is added; then it is stirred until it is completely dissolved.

After that, the remaining ingredients admitted, last the flavors. Again stirred until a homogeneous mass originated.

Metolose 60SH50 ^®: hydroxypropyl methylcellulose (HPMC)

Example 2:

Partially adhesive, disintegrating, gelling, delayed releasing film-like Preparation.

The production takes place accordingly as in Example 1.

Example 3:

Mucoadhesive, disintegrating, fast releasing film-like Preparation.

The production takes place accordingly as in Example 1.

Example 4:

Non-adhesive, disintegrating, fast releasing film-like Preparation.

Production: The solvent is heated and Mowiol 8-88 were added and dissolved therein. After cooling this Polyvinyl alcohol solution be stirred the remaining Ingredients added, finally the flavorings. The stirring process is continued until a homogeneous mass is obtained.

Example 5:

Mucoadhesive, non-decaying, delayed-release film-shaped Preparation.

Production: Eudragit ^® NE (Rohm Pharma GmbH) is dissolved in ethanol, and Gantrez ^® AN 169 is incorporated in portions. The mass is homogenized while heating; then the active ingredient is added.

Claims (25)

Process for the preparation of a film-shaped preparation for the transmucosal administration of nicotine, characterized in that it comprises a step in which the free base nicotine is converted into the corresponding salt by the addition of at least one acid and / or in that it comprises a step in which Nicotine salt (s) is selected from the group consisting of: fruit acid salts, in particular salts of citric acid, tartaric acid, malic acid, succinic acid, fumaric acid; Salts of acetic acid, lactic acid, ascorbic acid, adipic acid and phosphoric acid. Method according to claim 1, characterized in that that the Acid (s) is selected from the group, the fruit acids, like citric acid, Tartaric acid, malic acid, succinic acid, fumaric acid, and furthermore acetic acid, Lactic acid, salicylic acid, ascorbic acid, adipic acid and phosphoric acid comprises taking tartaric acid and salicylic acid are particularly preferred. Method according to claim 1 or 2, characterized that it the following steps include: - Production a coating composition using water or others Solvents; - Addition of nicotine and at least one acid, or / and adding nicotine in the form of one of the salts mentioned; - spreading the coating mass to a wet film; - Dry of the film. Method according to claim 3, characterized that at the preparation of the coating composition at least one monoterpene added is, preferably menthol. Method according to claim 3 or 4, characterized that at the preparation of the coating composition at least one polyalcohol added is, preferably from the propanediol, butanediol, glycerol and mygliol comprehensive group. Method according to claim 3, characterized that at the preparation of the coating composition at least one monoterpene and at least one polyalcohol is added. Method according to one of the preceding claims, characterized characterized in that the preparation of the coating composition, a cation exchanger and / or added a complexing agent becomes. Method according to one of the preceding claims, characterized characterized in that the preparation of the coating composition dexpanthenol is added. Method according to one of the preceding claims, characterized characterized in that the preparation of the coating composition at least one or more Added substances which are selected from the following substances or groups of substances: Flavorings, preferably peppermint or mint; sweetening substances; Dyes. Method according to one of the preceding claims, characterized in that the dried film is subsequently divided into area sections whose size is less than 10 cm ² , preferably less than 8 cm ² , particularly preferably less than 4 cm ² . in film form Preparation for transmucosal administration of nicotine according to any one of the preceding claims. in film form Preparation for transmucosal administration of nicotine, with at least a layer containing nicotine in salt form, with the nicotine salt (s) selected from the following group is / are: acid salts, in particular salts of citric acid, tartaric acid, malic acid, succinic acid, fumaric acid; Acetic acid, lactic acid, ascorbic acid, adipic acid and Phosphoric acid; Nicotine tartrate is most preferred. in film form Preparation according to claim 12 or 13, characterized in that it comprises at least one Layer containing nicotine or a salt of nicotine, wherein Nicotine or its salt are in the form of a complex, preferably as a complex with a cation exchanger. in film form Composition according to Claims 11 to 13, characterized in that it contains a or contains several substances, which are selected from the following substances or groups of substances: Acid (s), preferably fruit acids like citric acid, Tartaric acid, malic acid, succinic acid, fumaric acid; Acetic acid, lactic acid, salicylic acid, ascorbic acid, adipic acid and Phosphoric acid; Monoterpenes, preferably menthol; Polyalcohols, preferably propanediol, Butanediol, glycerin and mygliol; dexpanthenol; Flavorings, preferably Peppermint or mint; sweetening substances; Dyes. in film form Preparation according to one of the claims 11 to 14, characterized in that it is water-soluble or / and in aqueous Media is rapidly crumbling, but not mucoadhesive is. in film form Preparation according to one of the claims 11 to 14, characterized in that they mucoadhesive, however in aqueous Media is not or only partially soluble. in film form Preparation according to one of the claims 11 to 14, characterized in that they mucoadhesive and - in aqueous Soluble media or disintegrating, or - in aqueous Media gellable or swellable is. in film form Preparation according to one of the preceding claims, characterized that she translucent. in film form Preparation according to one of the preceding claims, characterized that she is not translucent. in film form Preparation according to one of the preceding claims, characterized that she within 20 minutes, preferably within 10 minutes, especially preferably within 5 minutes after application, the active ingredient Nicotin releases. in film form Preparation according to one of the preceding claims, characterized that she has two or more layers, it being preferred that at least one of the layers delayed Release drug has. Film-like preparation according to one of the preceding claims, characterized in that its area is less than 10 cm ² , preferably less than 8 cm ² , more preferably less than 4 cm ² . Use of a film-like preparation with the Active substance nicotine according to one of the preceding claims Smoking cessation. Use of a film-like preparation with the Active substance nicotine according to one of the preceding claims temporary or permanent nicotine substitution. Use of a film-like preparation with the Active substance nicotine according to one of the preceding claims, characterized characterized in that Preparation is administered orally, preferably for buccal administration.