DE102008011800A1 - Orally disintegrating film, useful e.g. to combat parasites in animals, preferably fish, exotic or wild animals, comprises a matrix made of a polymer of modified pea starch and an antiparasitic agent e.g. ivermectin and selamectin - Google Patents

Abstract

Orally disintegrating film comprises a matrix made of at least one polymer and at least one antiparasitic agent. An independent claim is included for a method for producing a film, comprising heating at least one modified starch in a solvent or solvent mixture and subsequently cool stirring the mixture, adding a second mixture comprising the same solvent or solvent mixture and at least an antiparasitic agent, homogeneously mixing the combined mixture and then forming into a film. ACTIVITY : Antiparasitic; Nematocide; Antihelmintic; Acaricide. MECHANISM OF ACTION : None given.

Description

The The present invention relates to an orally disintegrating film for the therapeutic use of antiparasitic agents in animals, and a method for producing the same and its use.

Orally disintegrating films ("orodispersible films", ODF) are used in the field of pharmacy to the body Active ingredients via the oral mucosa and the gastrointestinal tract systemically available. For that will be usually an active ingredient in a polymer or a polymeric matrix embedded, which on contact with water or saliva on surfaces of the oral cavity, such. B. the oral mucosa on the inside of the cheek, the palate, the tongue, the gums, etc. or the teeth, until it decays in a short time. A drug administration over ODF is particularly beneficial in individuals receiving other oral administration forms, such as As tablets, do not swallow, but spit out. simultaneously can ensure the administration of a specific dose through ODF be what z. B. in dosage forms with dissolved active ingredient can be problematic.

In Veterinary medicine is just a periodic application of drugs in some species problematic. An example this is the regular worming of cats, which is an orally administered drug in tablet form Spit very often. Here it is missing in particular at one suitable administration form for active substances used for parasite control be used.

The publication DE 699 19 554 T2 describes drug delivery systems for mucous membranes for use in veterinary medicine. These systems have the disadvantage that they must remain in the oral cavity for a long time in order to deliver the active ingredient in the desired dosage via the mucous membrane. In particular, they can be prematurely detached and spit out, which can cause uncertainties regarding the actual drug administration.

Other examples of transmucosal pharmaceutical dosage forms are described in US Pat DE 103 28 942 A1 and DE 102 56 774 A1 described.

task The present invention is the provision of a new oral Dosage form for the therapeutic use of antiparasitic agents Animals, which overcomes the disadvantages of the known administration forms. The dosage form should be in the mouth after contact with liquid or saliva and decay quickly there to spit out to avoid the dosage form or the active ingredient. The dosage form should be both chemically and physically stable. Another task The invention is a production method for a to provide such oral dosage form.

The The object is achieved by the subject matter of the invention according to solved independent claims. The dependent ones Claims make advantageous embodiments of the subject invention.

Of the The present invention is an orally disintegrating Film for the therapeutic use of an antiparasitic drug Animals which prefer a matrix of at least one polymer comprising a modified starch, and at least one Antiparasitic, d. H. an active ingredient in the field of antiparasitics includes.

Of the Film according to the invention is preferably single-layered and homogeneous. Preferably, the film sticks with saliva on the oral mucosa, until it decays quickly.

Prefers the movie is thin. Most preferably, the film has a Thickness of less than 1 mm, preferably from 0.2 to 0.8 mm, and most preferably from 0.3 to 0.5 mm. Is preferred the movie is flexible. Preferably, the film is stable. Especially preferred the film is thin, flexible and stable.

Especially "Film" in the sense of this invention means a single-layered film-like preparation containing a polymeric Matrix of at least one polymer, preferably comprising a modified starch, and at least one drug from the field of antiparasitics includes. The term monolayer film-shaped means Prepare a composition that is solid or in gel form, preferably a solid preparation which is in the form of a monolayer film. One-layer means that the film is in the form of a single layer is present, wherein the layer is preferably homogeneous. Alternatively, you can the film comprises two or more layers. The film is preferred a smooth surface.

A "matrix of at least one polymer" in the context of this invention denotes a matrix which consists of the polymeric molecules of at least one polymer z. B. produced by swelling in a suitable solvent, optionally with subsequent partial or complete drying, wherein molecules or particles of the at least one active ingredient and optional other components, either solid or dissolved, are included in the matrix thus prepared from at least one polymer. The at least one polymer preferably comprises a polymer selected from cellulose, modified cellulose, such as cellulose. B. hydroxypropyl lcellulose, starch, modified starch, such as. As hydroxypropyl starch, or one or more other natural or artificial polymers, such as. Eudragit.

"At least a polymer "means that the matrix is one or more Include polymers in any mixing ratios can. Preferably, the matrix comprises one, two or three polymers in any mixing ratios. In a particularly preferred Embodiment, the matrix consists of a polymer comprising a modified starch. In another particularly preferred Embodiment, the matrix consists of a polymer comprising two modified starches or one modified starch and another polymer. Particularly preferably, this comprises at least a polymer is a modified pea starch.

"Orally disintegrating "means that the invention Film in the oral cavity under the influence of water or saliva disintegrates or dissolves. Preferably, the sticks Film according to the invention in contact with saliva or with a surface of the oral cavity wetted with saliva, preferably the oral mucosa, in particular on the inside of the cheek, the palate, the tongue, the gums, etc. or the teeth, at this surface and disintegrates within 10 to 180 seconds after the first contact with saliva, continue preferably within 20 to 120 seconds, and more preferably within 30 to 60 seconds. This time is generally too short for an animal to spit out the movie.

There the film sticking in the mouth quickly dissolves, the drug contained is not only transmucosal the mucous membrane is absorbed, but also released to the saliva, and subsequently swallowed. The latter is particularly advantageous because So also an active ingredient administration is ensured, if the Film does not stick to a mucous membrane but, for example, to a tooth. This is not just the administration of the drug ensured in the desired dose, but also the application The film in the mouth makes it easier because he is not necessarily on one Mucosa must be glued.

One Animal in the sense of this invention is preferably a vertebrate, on preferably a mammal, and more preferably a domestic or farm animal. Examples are fish, exotic or Wild animals, such. B. circus or zoo animals such as martens, Foxes, ferrets, etc., pets, such. Dogs, cats etc.

Of the Term antiparasitic or antihelmonic referred to in the sense this invention any drug that can act against parasites, which can infest an animal. examples for Parasites are nematodes, worms and other endoparasites, and ectoparasites, such as fleas, lice, mites, Ticks, and the like.

Prefers Antiparasitic is an antiparasitic drug administered orally can be. Preferred are macrocyclic lactones, such as Avermectins. Most preferably, the antiparasitic is selected from the group consisting of ivermectin, selamectin, doramectin and abamectin. Especially preferred is the antiparasitic agent ivermectin. Preference is given to the antiparasitic drug with a dosage of 0.2 to 0.4 mg per kg of the animal administered.

"At least an antiparasitic "means that the invention Film contains one or more antiparasitic agents, preferably one, two or three antiparasitic agents, and more preferably exactly one Antiparasitic agent.

It it was found that the film according to the invention a very advantageous combination of mechanical stability of the film and rapid release of the drug offers.

Prefers the at least one modified starch is a modified one Pea starch. A modified pea starch in the The meaning of this invention is a pea starch, the usual Process acetylated, hydroxylated, hydroxymethylated and / or hydroxypropylated has been. Preferably, the modified pea starch is a hydroxypropylated pea starch.

It It was surprisingly found that made this special modified pea starch according to the invention Produce film, the most advantageous Properties of the oral therapeutic use of antiparasitics in animals shows. So a film sticks on the basis of the modified Pea starch especially good on contact with saliva the oral mucosa until it disintegrates within 30 to 60 seconds.

Prefers is the active ingredient in the field of antiparasitic a parasiticide for internal use, more preferably an active ingredient from the group of macrocyclic lactones or avermectins such as ivermectin, Selamectin, doramectin and abamectin, and particularly preferred ivermectin. It has been found that these agents are particularly good in combination with an orally disintegrating film based on modified pea starch can be applied.

The film according to the invention may additionally comprise one or more further components which are selected independently of one another from solvent, solvent mixture, soft emulsifier, circulatory enhancer, sweetener, taste masker (such as cyclodextrins), dye and flavor.

Examples suitable solvents are water, alcohols, especially ethanol. Preference is given to water and ethanol.

Examples for solvent mixtures are binary or Ternary mixtures of the abovementioned solvents. Preference is given to a mixture of water and alcohol, in particular ethanol, with a mixture of 75% water and 25% ethanol being particularly preferred is. Unless otherwise indicated, all percentages are by weight. Such solvent mixtures of water and alcohol have the advantage that they not only good solubility of the Ensure film components, but also fast drying allow the film by evaporation.

preferred Examples of plasticizers are dibutyl sebacate and glycerin. Particularly preferred is a mixture of dibutyl sebacate and glycerol as Softener used. It was found to be using of dibutyl sebacate and glycerin according to the invention Produce low-strength films that are extra special have high flexibility but are nevertheless stable. In particular are films made using dibutyl sebacate and glycerine smoother and less brittle.

Examples for blood circulation are common Perfusion promoter, preferably menthol.

Examples sweeteners are common sweeteners, as preferred is sugar or sorbitol.

Examples for flavoring agents usual flavors are preferred bitter flavors such as grapefruit or peppermint. In animals should not use essential oils if possible be used. For cats can also be valerian or a other amine group-wide flavoring, such as Eudragit, be used, as these spit out of the dissolved Effectively prevent active ingredient.

Examples for emulsifiers are common emulsifiers, such as for example soy lecithin or tween.

Prefers the film according to the invention comprises 60 to 85% by weight the at least one modified starch, more preferred 60 to 80 wt .-%, and particularly preferably 65 to 75 wt .-%. If the Film contains more than 85 wt .-% starch, it becomes too brittle, whereas a starch content of less than 60% by weight does not give stable films.

The film according to the invention preferably comprises 1 to 20% by weight of the at least one antiparasitic agent, more preferably 3 to 15% by weight, and particularly preferably 5 to 10% by weight. This makes it possible to produce films of acceptable size and active ingredient content. Preferably, a film according to the invention has a weight of about 20-110, better 40-80 mg per 10 cm ² .

In In a particularly preferred embodiment, the Film according to the invention 60 to 70 wt .-% of at least a modified starch, 5 to 10% of the at least one Antiparasitic, 5 to 20% by weight plasticizer, 1 to 3% by weight perfusion promoter, 1 to 10% by weight of sweet and / or flavorings, and 0.1 to 1 wt .-% emulsifier.

Prefers the film according to the invention additionally comprises a suitable carrier film which is on a surface of the film is laminated or laminated on the dried film is. Examples of suitable carrier films are Films made of plastics, such as. As PE, PP, PETP, or with these Plastics coated carrier such. As paper, as long as these carrier films are not too stiff. A carrier foil advantageously improves the handling of the film during further processing, z. B. when cutting or punching, or during administration.

Of the Film according to the invention preferably has a film thickness less than 1 mm, preferably from 0.2 to 0.8 mm, and especially preferably from 0.3 to 0.5 mm. An inventive Film with this film thickness is sufficiently flexible and stable.

Of the Film according to the invention may be of any known form have, for. B. a round, polygonal or square shape.

The film according to the invention preferably has a size of 2.5 to 10 cm ² .

Of the Film according to the invention preferably comprises a dose from 5 to 7 mg / unit.

Farther the subject of the invention is a production process for a film according to the invention described above, in particular an orally disintegrating film for therapeutic use of at least one antiparasitic drug in animals that has a matrix of at least one modified starch and at least an active ingredient in the field of antiparasitic agents.

In the process for producing a film according to the invention, at least one modified starch is preferably heated in a solvent or solvent mixture and then stirred cold; then a second mixture will dissolve the same medium or solvent mixture and at least one active ingredient from the range of Antiparasitika, is added and the combined mixture is mixed homogeneously, and then formed into a film.

there are the definitions and preferred embodiments as stated above.

Prefers is used in the process according to the invention as at least a modified starch is a modified pea starch used.

Prefers is used in the process according to the invention as at least used an antiparasitic ivermectin.

Prefers comprises in the inventive method the second mixture additionally one or more further components, which are selected independently of each other Plasticizer, emulsifier, perfusion promoter, sweetener, Geschmackskaschierer, such as. As cyclodextrins, dye and flavoring.

In a preferred embodiment of the invention Procedure, the film is shaped by the combined mixture coated on a carrier film and dried. Preferred carrier films are films made of plastics, such. As PE, PP, PETP, or with these Plastics coated carrier such. As paper, as long as these carrier films are not too stiff.

Prefers is used in the process according to the invention as a solvent Water or as a solvent mixture a water / alcohol mixture used. Such solvent mixtures of water and Alcohol has the advantage of not only good solubility ensure the film components, but also fast drying allow the film by evaporation.

After all The object of the present invention is the use of an above described film of the invention, in particular of an orally disintegrating film for the therapeutic use of at least one antiparasitic in animals, consisting of a matrix at least one modified starch and at least one Active substance in the field of antiparasitic agents.

In The following is the present invention by the following Examples explained in more detail, but without the scope of the invention thereby restrict.

Examples

Provided Unless otherwise indicated, all data are in% by weight the dried film. It is assumed that a possibly contained Solvent component when drying the film completely evaporated.

example 1

A composition was prepared according to the following recipe by heating the starch in a solvent mixture of 75% water / 25% ethanol at 80 ° C under vacuum and then cold stirring at room temperature. Then, a second mixture of the remaining Inhalststoffen is also prepared in a solvent mixture of 75 water / 25% ethanol, and added to the first mixture. The combined mixture is mixed homogeneously, and then formed into a 0.2 to 0.8 mm thick film by coating on a PETP supporting film and drying at 20 to 60 ° C. The film is cut into pieces with dimensions of 2.5 to 10.0 cm ² .

• 70% Stärke (1. Polymer, modifizierte Erbsenstärke)
• 1% Eudragit (2. Polymer, Aromastoff)
• 10% Dibutylsebacat (Weichmacher)
• 5% Glycerin (Weichmacher)
• 2,5% Menthol (Durchblutungsförderer)
• 2,5% Zucker (Süßstoff)
• 0,4% Tween 80 (Emulgator)
• 0,4% Soja Lecithin (Emulgator)
• 8,2% Ivermectin (Wirkstoff, Antiparasitikum)

The resulting film is flexible and stable, but adheres to the oral mucosa on contact with saliva until it disintegrates within 30 to 60 seconds.

• 70% starch (1st polymer, modified pea starch)
• 1% Eudragit (2nd polymer, flavoring)
• 10% dibutyl sebacate (plasticizer)
• 5% glycerin (plasticizer)
• 2.5% menthol (circulation enhancer)
• 2.5% sugar (sweetener)
• 0.4% Tween 80 (emulsifier)
• 0.4% soy lecithin (emulsifier)
• 8.2% ivermectin (active ingredient, antiparasitic)

Example 2

First, a coating composition is prepared as described below:
Water, starch and sugar are combined and heated to 70 ° C for 3 hours (solution 1). The starch gel is allowed to stand and cooled to room temperature. Glycerine, methanol, dimethyl sebacate, tween, soy lecithin, ethanol and ivermectin are weighed in separately (solution 2). After cooling from solution 1, solution 2 is added and stirred for 15 minutes under vacuum.

Film production by coating:

The film is produced on a continuous coating plant, consisting of an unwinding roll, from which the carrier film is unwound; a squeegee, over which the coating composition is applied to the carrier film; an oven through which the carrier sheet is pulled through and the mass is dried; an optional laminating roller through which a second carrier film is coated on the free side of the dried film from the coating composition; and a Aufwi ckelwalze on which the film produced (on the support or as a laminate) is wound on a sleeve. The coating width is variable, and is preferably between 50 to 200 mm. The film thickness is 0.2 to 0.8 mm.

Of the resulting film has comparable properties as in Example 1 on.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• - DE 69919554 T2 [0004]
• - DE 10328942 A1 [0005]
• - DE 10256774 A1 [0005]

Claims (15)

Oral decaying film for therapeutic use from an antiparasitic disease in animals, comprising a matrix at least one polymer, and at least one antiparasitic. Film according to claim 1, characterized in that the at least one polymer comprises a modified starch, in particular a modified pea starch. Film according to claim 1 or 2, characterized that at least one antiparasitic drug is selected from the group consisting of ivermectin, selamectin, doramectin and abamectin. Film according to claim 3, characterized in that the antiparasitic is ivermectin. A film according to any one of claims 1 to 4, characterized characterized in that it comprises one or more further components, which are selected independently of each other Solvent, solvent mixture, plasticizer, emulsifier, Circulation enhancer, sweetener, taste masker, dye and flavoring. Film according to one of claims 1 to 5, characterized characterized in that it contains 60 to 85% of the at least one modified Strength includes. A film according to any one of claims 1 to 6, characterized characterized in that it contains 1 to 20% of the at least one antiparasitic includes. A film according to any one of claims 1 to 7, characterized in that it additionally has a carrier film includes. Process for producing a film after a of claims 1 to 8, wherein at least one modified Starch in a solvent or solvent mixture heated and then stirred cold, with a second mixture comprising the same solvent or Solvent mixture and at least one Antiparasitikum, added is added, the combined mixture is mixed homogeneously, and then a film is formed. Method according to claim 9, characterized that the at least one modified starch is a modified one Pea starch is. Method according to claim 9 or 10, characterized that the at least one antiparasitic is ivermectin. Method according to one of claims 9 to 11, characterized in that the second mixture in addition includes one or more other components that are independent be selected from one another from plasticizer, emulsifier, Circulation enhancer, sweetener, taste masker, dye and flavoring. Method according to one of claims 9 to 12, characterized in that the film is formed by the united Mixture coated on a carrier film and dried becomes. Method according to one of claims 9 to 13, characterized in that the solvent is water or the solvent mixture is a water / alcohol mixture. Use of a film according to claim 1 to 8 for controlling parasites in animals.