ORAL THIN FILM

Description

[0001] The present invention relates to an oral thin film comprising at least one matrix polymer and at least one pharmaceutically active agent, wherein the at least one pharmaceutically active agent is an acid or a base and wherein the at least one pharmaceutically active agent is in the form of a mixture comprising the at least one pharmaceutically active agent both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt, a method for its preparation, and the use of such an oral thin film as a pharmaceutical drug.

[0002] Oral thin films are thin films containing at least one pharmaceutically active ingredient that are placed directly into the oral cavity or applied to the oral mucosa, where they dissolve or swell, releasing the active ingredient. These are primarily thin, single- or multi-layered, polymer-based films containing the active ingredient, which, when applied to the mucosa, especially the oral mucosa, can deliver the active ingredient directly into it. The excellent blood supply of the oral mucosa ensures rapid absorption of the active ingredient into the bloodstream. This delivery system has the advantage that the active ingredient is largely absorbed through the mucosa, thus avoiding the "first-pass metabolism" that occurs with conventional tablet-based drug administration. The active ingredient can be dissolved, emulsified, or dispersed within the film.

[0003] The pH value is a crucial factor for the absorption of a pharmaceutically active substance through a mucous membrane, as well as for the stability of a pharmaceutically active substance and the overall stability of a pharmaceutical composition. In particular, when an oral thin film dissolves in a patient's mouth, the resulting pH value at the point of dissolution is critical for the absorption of the pharmaceutically active substance.

[0004] Desired pH values ​​are typically adjusted by adding acids or bases, or by using buffer systems, which, however, can negatively affect the pharmaceutical formulation. Neutralizing an active ingredient by adding acid or base to the formulation produces a salt as a byproduct, which negatively impacts the formulation since it serves no further function. In particular, the resulting salt increases the basis weight of an oral thin film and can also negatively affect the stability and taste of the formulation. The same applies to the use of buffer systems.

[0005] DE 10 2017 129012 discloses an oral thin film comprising at least one cellulose derivative and at least one pharmaceutically active ingredient, wherein the at least one pharmaceutically active ingredient has a water solubility of at most 50 g / L at 20°C and a pH of 6 to 7 and is contained in the oral thin film in an amount of at least 20% by weight, based on the total weight of the oral thin film.

[0006] WO 2014 / 020155 discloses methods and compositions for the treatment of pain.

[0007] DE 103 28 942 discloses film-shaped dosage forms for the transmucosal administration of active substances to the human or animal body, characterized by an adjustment or approximation of the pH value of the base mass provided for the manufacture of the dosage form, comprising a solvent or solvent mixture, at least one matrix-forming polymer and at least one active substance, to the physiological pH value of the mucous membrane intended for application.

[0008] The object of the present invention is to overcome the aforementioned disadvantages of the prior art. In particular, the object of the present invention is to provide an oral thin film whose pH value, especially the pH value after dissolution of the oral thin film, can be advantageously adjusted without the need to add further acids, bases, or buffer systems to the oral thin film. Furthermore, the oral thin film should allow the pH value in the patient's saliva to be adjusted over the widest possible range and remain as stable as possible. In addition, the oral thin film should be as simple and economical to produce as possible.

[0009] The above problem is solved by a multilayer oral thin film according to claim 1, in particular by an oral thin film comprising at least one matrix polymer and at least one pharmaceutically active agent, wherein the at least one pharmaceutically active agent is an acid or a base, characterized in that the at least one pharmaceutically active agent is in the form of a mixture comprising the at least one pharmaceutically active agent both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt, wherein the mixture comprising the at least one pharmaceutically active agent both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt,comprising at least one pharmaceutically active ingredient in the form of the free acid or base and at least one pharmaceutically active ingredient in the form of a pharmaceutically acceptable salt of the free acid or base in a molar ratio of 3:1 to 1:3.

[0010] Such an oral thin film is advantageous because the mixture, which comprises the at least one pharmaceutically active ingredient in both the form of the free acid or base and in the form of a pharmaceutically acceptable salt, provides a buffer system within the oral thin film without the need to add any further acids, bases, or buffer substances. The pH of the formulation can be adjusted by modifying the ratio of the at least one pharmaceutically active ingredient in the form of the free acid or base to the at least one pharmaceutically active ingredient in the form of a pharmaceutically acceptable salt. Since no further acid, base, or buffer substance needs to be added to such a formulation, the formulation, and thus the final oral thin film, is not negatively affected by the formation of salts during neutralization or by the presence of a buffer system.

[0011] For the definition of acid and base, the Brønsted acid-base concept, known to those skilled in the art, is to be applied in particular. Thus, the oral thin film according to the invention comprises, in particular, at least one pharmaceutically active ingredient which, according to the Brønsted acid-base concept, is an acid or a base.

[0012] In this document, "comprehensive" can also mean "consisting of".

[0013] The oral thin film according to the invention is further preferably characterized in that the at least one matrix polymer comprises a water-soluble polymer.

[0014] Water-soluble polymers encompass chemically very diverse natural or synthetic polymers, whose common characteristic is their solubility in water or aqueous media. A prerequisite is that these polymers possess a sufficient number of hydrophilic groups to ensure water solubility and are not cross-linked. The hydrophilic groups can be non-ionic, anionic, cationic, and / or zwitterionic.

[0015] Water-soluble is preferably understood to mean a solubility of greater than 100 g / L in water at 25°C.

[0016] The at least one water-soluble polymer is preferably selected from the group comprising starch and starch derivatives, dextrans, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, ethyl or propylcellulose, polyacrylic acids, polyacrylates, polyvinylpyrrolidones, vinylpyrrolidone / vinyl acetate copolymers, polyvinyl alcohols, polyethylene oxide polymers, polyacrylamides, polyethylene glycols, gelatin, collagen, alginates, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan and natural gums, polyvinyl alcohol-polyethylene glycol graft copolymers, wherein polyvinyl alcohols are particularly preferred.

[0017] The oral thin film according to the invention is further preferably characterized in that the at least one matrix polymer, preferably the water-soluble polymer, is present in an amount of 10 to 90 wt.%, preferably 20 to 60 wt.%, particularly preferably 30 to 50 wt.%, based on the total weight of the oral thin film.

[0018] The oral thin film according to the invention is preferably characterized in that, in addition to the mixture comprising the at least one pharmaceutically active ingredient in the form of the free acid or base as well as in the form of a pharmaceutically acceptable salt, the oral thin film does not comprise any further acid, base, salt and / or buffer systems.

[0019] In particular, the oral thin film should not contain hydrochloric acid, NaOH, KOH, Na2CO3, NaHCO3, K2CO3 and / or sulfuric acid.

[0020] Furthermore, the oral thin film according to the invention should not contain any NaCl, KCl, phosphate buffer, TRIS buffer, citrate buffer, carbonate buffer, sulfate buffer, borate buffer and / or ammonium buffer.

[0021] The at least one pharmaceutically active substance is not subject to any restrictions other than being an acid or a base, but is preferably selected from all pharmaceutically active substances suitable for oral and / or transmucosal administration.

[0022] Preferably, the oral thin film according to the invention is characterized in that the at least one pharmaceutically active ingredient, if it is an acid, has a pKa of 3 to 11, preferably of 4 to 9.

[0023] Preferably, the oral thin film according to the invention is characterized in that the at least one pharmaceutically active ingredient, if it is a base, has a pKa b of 3 to 11, preferably of 4 to 9.

[0024] Preferably, the oral thin film according to the invention is characterized in that the at least one pharmaceutically active ingredient comprises a carboxyl group, an amino group, a sulfone group and / or a phosphonate group.

[0025] Preferred active ingredients are selected from the group comprising the drug classes of analgesics, hormones, hypnotics, sedatives, antiepileptics, stimulants, psychoneurotropics, neuromuscular blockers, antispasmodics, antihistamines, antiallergics, cardiotonics, antiarrhythmics, diuretics, hypotensives, vasopressors, antidepressants, antitussives, expectorants, thyroid hormones, sex hormones, antidiabetics, antitumor agents, antibiotics, chemotherapeutic agents and narcotics, although this group is not exhaustive.

[0026] Ketamine is particularly preferred as the at least one pharmaceutically active ingredient.

[0027] Ketamine is understood to mean (S)-(±)-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one, (R)-(±)-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one, as well as the racemate (RS)-(±)-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one.

[0028] (S)-Ketamine is particularly preferred as the only stereoisomer of ketamine, since the analgesic and anesthetic potency of (S)-ketamine is about three times higher than that of the (R)-form.

[0029] Preferably, the oral thin film according to the invention is characterized in that the mixture, which comprises the at least one pharmaceutically active agent both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt, comprises ketamine as the free base and ketamine hydrochloride, preferably (S)-ketamine as the free base and (S)-ketamine hydrochloride.

[0030] By mixing ketamine as a free base and ketamine hydrochloride, suitable pH values ​​can be adjusted in particular without the need to add further acids, bases or buffer systems.

[0031] The active ingredient content in the oral thin film can vary within relatively wide limits. A range of 10 to 60 wt.%, based on the total weight (dry weight) of the oral thin film, can be considered suitable. In one embodiment, the proportion of active ingredient in the oral thin film is closer to the lower end of this range, for example, if the active ingredient has a strongly unpleasant taste that must be masked with a larger quantity of taste-masking agents. In this case, a range of 10 to 40 wt.% can be considered suitable. In another embodiment, the proportion of active ingredient in the dosage form according to the invention is closer to the upper end, with a content of 40 to 60 wt.% and, in particular, a content of 45 to 55 wt.% being considered especially preferred.

[0032] The amount of pharmaceutically active substance refers to the mixture which includes the at least one pharmaceutically active substance both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt, i.e., the sum of the amounts of the at least one pharmaceutically active substance in the form of the free acid or base and the amount of the at least one pharmaceutically active substance in the form of a pharmaceutically acceptable salt thereof.

[0033] The oral thin film according to the invention is therefore particularly preferred in that the mixture comprising the at least one pharmaceutically active ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt is present in an amount of 35 to 60 wt.%, based on the total weight of the oral thin film.

[0034] Ketamine is particularly preferably present as the free base and as a pharmaceutically acceptable salt thereof, in particular ketamine as the free base and as ketamine hydrochloride, preferably (S)-ketamine as the free base and as (S)-ketamine hydrochloride, in total in an amount of 35 to 60 wt.%, based on the total weight of the oral thin film.

[0035] To adjust the pH value, the molar ratio of at least one pharmaceutically active substance in the form of the free acid or base and at least one pharmaceutically active substance in the form of a pharmaceutically acceptable salt thereof is crucial.

[0036] The oral thin film according to the invention is therefore preferably characterized in that the mixture comprising the at least one pharmaceutically active agent in the form of both the free acid or base and in the form of a pharmaceutically acceptable salt comprises the at least one pharmaceutically active agent in the form of the free acid or base and the at least one pharmaceutically active agent in the form of a pharmaceutically acceptable salt in a molar ratio of 1.5 to 1 to 1:1.5, preferably about 1:1 and particularly preferably 1:1.

[0037] Preferably, the molar ratio of ketamine as free base and ketamine as pharmaceutically acceptable salt is 3:1 to 1:3, preferably 1.5 to 1 to 1:1.5, particularly preferably about 1:1 and most particularly preferably 1:1.

[0038] The oral thin film according to the invention most preferably comprises ketamine as free base and ketamine hydrochloride in a molar ratio of 3:1 to 1:3, preferably 1.5 to 1 to 1:1.5, particularly preferably about 1:1 and most preferably 1:1.

[0039] In another preferred embodiment, the oral thin film according to the invention comprises (S)-ketamine as free base and (S)-ketamine hydrochloride in a molar ratio of 3:1 to 1:3, preferably 1.5 to 1 to 1:1.5, particularly preferably about 1:1 and most particularly preferably 1:1.

[0040] The oral thin film according to the invention is preferably further characterized in that the oral thin film has a pH of 3.5 to 9.5, preferably of 4.5 to 8.8.

[0041] This refers to the pH value (at 20°C) that is established in a solution for which the oral thin film is dissolved in pure water.

[0042] The multilayer oral thin film according to the invention is further preferably characterized in that the matrix layer comprises at least one excipient selected from the group consisting of colorants, flavorings, sweeteners, plasticizers, flavor-masking agents, emulsifiers, enhancers, pH regulators, humectants, preservatives and / or antioxidants.

[0043] Each of these auxiliary materials is preferably contained in the matrix layer in an amount of 0.1 to 40 wt.%, preferably 0.1 to 30 wt.%, particularly preferably 0.1 to 15 wt.%, most preferably 0.1 to 10 wt.% or 0.1 to 5 wt.%, based on the total weight of the matrix layer.

[0044] The multilayer oral thin film according to the invention is in principle not limited in the number of layers it contains.

[0045] Thus, embodiments are conceivable in which the oral thin film according to the invention has several layers containing active ingredients.

[0046] In one embodiment, the oral thin film according to the invention can represent a substantially smooth film.

[0047] Preferably, the oral thin film according to the invention is characterized in that it is in the form of a solidified foam having cavities.

[0048] The cavities and the associated larger surface area of ​​the films particularly facilitate the entry of water, saliva or other body fluids into the interior of the dosage form, thus accelerating the dissolution of the dosage form and the release of the active ingredient.

[0049] Furthermore, with a rapidly absorbed drug, the transmucosal absorption can be improved by the rapid dissolution of the matrix layer.

[0050] Secondly, the wall thickness of the aforementioned cavities is preferably small, since these, for example, represent solidified bubbles, so that rapid dissolution or destruction of these cavities takes place.

[0051] Another advantage of this embodiment is that, despite the comparatively high basis weight, faster drying can be achieved by manufacturing it as a foam than with a comparable non-foamed composition.

[0052] Preferably, the oral thin film according to the invention is characterized in that the cavities are isolated from each other and preferably have the form of bubbles, wherein the cavities are filled with air or a gas, preferably with an inert gas, particularly preferably with nitrogen, carbon dioxide, helium or a mixture of at least two of these gases.

[0053] According to another embodiment, the cavities are provided to be interconnected, preferably by forming a continuous channel system penetrating the matrix.

[0054] Preferably, the aforementioned cavities have a volume fraction of 5 to 98%, more preferably 40 to 80%, based on the total volume of the matrix layer. This favorably influences the desired effect of accelerating the dissolution of the oral thin film.

[0055] Furthermore, surfactants or surface-active substances can be added to the oral thin film for foam formation or to the obtained foam before or after drying in order to improve the stability of the foam before or after drying.

[0056] Another parameter influencing the properties of the oral thin film according to the invention is the diameter of the cavities or bubbles. The bubbles or cavities are preferably generated using a foaming machine, with which the diameter of the bubbles can be adjusted within a wide range, almost arbitrarily. Thus, the diameter of the bubbles or cavities can range from 0.01 to 60 µm. A diameter in the range of 10 to 50 µm is particularly preferred.

[0057] The oral thin film according to the invention preferably has an area of ​​0.5 cm² to 10 cm², particularly preferably of 1.5 cm² to 8 cm².

[0058] The basis weight of the oral thin film according to the invention is preferably at least 10 g / m², more preferably at least 20 g / m² or at least 30 g / m², or most preferably at least 50 g / m² or is less than or equal to 400 g / m², more preferably less than or equal to 350 g / m² or less than or equal to 300 g / m², or most preferably less than or equal to 150 g / m². Preferably the basis weight is 10 to 400 g / m², more preferably 20 to 350 g / m² or 30 to 300 g / m², and most preferably 50 to 200 g / m².

[0059] Preferably, the oral thin film according to the invention has a thickness of about 10 µm to about 500 µm, particularly preferably of about 20 µm to about 300 µm.

[0060] The present invention further relates to a method for producing the oral thin film according to the invention, comprising the steps of: a) Preparing a solution, dispersion, or melt containing at least one matrix polymer and at least one pharmaceutical active ingredient in the form of a mixture comprising the at least one pharmaceutically active ingredient in both the form of the free acid or base and in the form of a pharmaceutically acceptable salt, wherein the mixture comprising the at least one pharmaceutically active ingredient in both the form of the free acid or base and in the form of a pharmaceutically acceptable salt comprises the at least one pharmaceutically active ingredient in the form of the free acid or base and the at least one pharmaceutically active ingredient in the form of a pharmaceutically acceptable salt of the free acid or base in a molar ratio of 3:1 to 1:3, b) streaking the solution, dispersion, or melt from step a) to obtain a film, and c) drying the film from step b) to obtain an oral thin film.

[0061] The method according to the invention preferably does not include a step in which the at least one pharmaceutically active ingredient is wholly or partially neutralized by the addition of acid or base.

[0062] The method according to the invention is preferably also characterized in that no further buffer system is present in the oral thin film.

[0063] The method according to the invention preferably comprises an optional step a1), which includes foaming the solution, dispersion or melt from step a) by introducing a gas or gas mixture, by chemical gas generation or by expanding a dissolved gas. It is clear to those skilled in the art that step a1) is only necessary if the oral thin film is to be in the form of a solidified foam containing cavities.

[0064] Furthermore, the present invention relates to an oral thin film, as described above, or obtainable by the method described above, as a medicinal product.

[0065] The present invention further relates to an oral thin film, as described above or obtainable by the method described above, wherein a mixture of ketamine as free base and ketamine as a pharmaceutically acceptable salt, preferably ketamine as free base and ketamine hydrochloride, in particular (S)-ketamine as free base and (S)-ketamine as a pharmaceutically acceptable salt, particularly preferably (S)-ketamine as free base and (S)-ketamine hydrochloride, is used for use in the treatment of pain and / or depression, in particular for reducing the risk of suicide, and / or for use as a general anesthetic, preferably for induction and maintenance of general anesthesia or as an adjunct to regional anesthesia and / or as an analgesic.

[0066] The preferred embodiments listed above for the multilayer oral thin film according to the invention also apply to the method according to the invention, the multilayer oral thin film obtained by this method and its use as a medicinal product.

[0067] The invention is explained in more detail below using non-limiting examples. Examples

[0068] During the development of oral thin films containing ketamine as the pharmaceutically active ingredient, it was found that the pH value in the patient's oral cavity can influence drug release. To bring the ketamine hydrochloride used, which has a pH of 5.32 in the tested formulation (see Table 1), into a partially neutralized state, it was reacted with NaOH. This led to the formation of NaCl, which affects the formulation because it must be taken into account in the composition. By formulating a mixture of ketamine as the free base and ketamine hydrochloride in a 1:1 molar ratio, essentially the same pH value as with an equimolar 50% neutralization with NaOH could be achieved. Table 1 Formulation [wt.%] ingredient function 1 2 3 4 (S)-Ketamine HCl Active ingredient 50,00 50,00 --- 25,00 (S)-Ketamine Base Active ingredient --- --- 43,35 21,68 Polyvinyl alcohol Matrix polymer 39,10 35,85 46,15 42,82 NaOH pH regulator --- 3,65 --- --- Saccarin Na Flavor correction 1,00 1,00 1,00 1,00 Sucrose Flavor correction 2,00 2,00 2,00 2,00 Cherry Flavor Flavor correction 3,00 3,00 3,00 3,00 Glycerol Humectant 4,50 2,71 4,50 4,50 FD&C red dye 0,40 --- --- --- PH value Measured as dissolved OTF in dematerialized water tempered to 32 °C (blank pH 7.12) 5,32 6,15 7,97 6,11 PH value Measured as resolved OTF at 32 °C 5,49 6,43 7,32 6,50 tempered human saliva (blank value pH 6.95)

[0069] Oral thin films with the composition shown in Table 1 were prepared as follows. The active ingredient or active ingredient mixture was placed on the surface and an aqueous solution of the matrix polymer was added. The remaining ingredients were then stirred in. The solution was spread out and dried to obtain an oral thin film.

[0070] It can be seen that the mixture of (S)-ketamine (free base) and (S)-ketamine hydrochloride (4) has essentially the same pH as the neutralized formulation (2).

[0071] Advantages of formulation (4), comprising (S)-ketamine (free base) and (S)-ketamine hydrochloride without the addition of NaOH, are: No salt formation through neutralization and no associated negative effects.

[0072] Due to the lower molecular weight of (S)-ketamine (free base), the proportion of active ingredient used is lower, meaning that proportions of other components can be increased relative to it.

[0073] (S)-Ketamine (free base) and the corresponding protonated compound form a buffer system.

[0074] (S)-Ketamine (free base) is further stabilized by the HCl.

[0075] Potential improvement in taste, as the pH value can influence the taste (acidic or alkaline (= soapy)).

[0076] By varying the amount of (S)-ketamine (free base) and (S)-ketamine hydrochloride, any pH value between that of the base and the salt can be set.

Claims

1. An oral thin comprising at least one matrix polymer and at least one active pharmaceutical ingredient, wherein the at least one active pharmaceutical ingredient is an acid or a base, characterised in that the at least one active pharmaceutical ingredient is present in the form of a mixture which comprises the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt, wherein the mixture comprising the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt comprises the at least one active pharmaceutical ingredient in the form of the free acid or base and the at least one active pharmaceutical ingredient in the form of a pharmaceutically acceptable salt of the free acid or base in a molar ratio of 3:1 to 1:3.

2. The oral thin film according to claim 1, characterised in that the at least one matrix polymer comprises a water-soluble polymer.

3. The oral thin film according to any one of the preceding claims, characterised in that the at least one matrix polymer is selected from the group comprising starch and starch derivatives, dextrans, cellulose derivatives, such as carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, sodium carboxymethyl cellulose, ethyl or propyl cellulose, polyacrylic acids, polyacrylates, polyvinylpyrrolidones, polyvinyl alcohol-polyethylene glycol graft copolymers, vinylpyrrolidone / vinyl acetate copolymers, polyvinyl alcohols, polyethylene oxide polymers, polyacrylamides, polyethylene glycols, gelatines, collagen, alginates, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan, and natural gums.

4. The oral thin film according to any one of the preceding claims, characterised in that the at least one matrix polymer is present in an amount of 10 to 90 wt.%, in relation to the total weight of the oral thin film.

5. The oral thin film according to any one of the preceding claims, characterised in that the oral thin film, besides the mixture comprising the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt, does not comprise any further acids, bases, salts and / or buffer systems.

6. The oral thin film according to any one of the preceding claims, characterised in that the at least one active pharmaceutical ingredient comprises a carboxyl group, an amino group, a sulfonyl group and / or a phosphonate group.

7. The oral thin film according to any one of the preceding claims, characterised in that the at least one active pharmaceutical ingredient is selected from the group comprising the active ingredient classes of analgesics, hormones, hypnotics, sedatives, antiepileptics, analeptics, psychoneurotropic drugs, neuro-muscle blockers, antispasmodics, antihistamines, antiallergics, cardiotonics, antiarrhythmics, diuretics, hypotensives, vasopressors, antidepressants, antitussives, expectorants, thyroid hormones, sexual hormones, antidiabetics, antitumour active ingredients, antibiotics, chemotherapeutics and narcotics.

8. The oral thin film according to any one of the preceding claims, characterised in that the at least one active pharmaceutical ingredient comprises ketamine, especially preferably (S)-ketamine.

9. The oral thin film according to any one of the preceding claims, characterised in that the mixture comprising the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt comprises ketamine as free base and ketamine hydrochloride, preferably (S)-ketamine as free base and (S)-ketamine hydrochloride.

10. The oral thin film according to any one of the preceding claims, characterised in that the mixture comprising the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt is present in an amount of 35 to 55 wt.%, in relation to the total weight of the oral thin film.

11. The oral thin film according to any one of the preceding claims, characterised in that the mixture comprising the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt comprises the at least one active pharmaceutical ingredient in the form of the free acid or base and the at least active pharmaceutical ingredient in the form of a pharmaceutically acceptable salt in a molar ratio of 1.5:1 to 1:1.5.

12. The oral thin film according to any one of the preceding claims, characterised in that the oral thin film has a pH of 3.5 to 9.5, preferably of 4.5 to 8.

813. The oral thin film according to any one of the preceding claims, characterised in that the oral thin film further comprises at least one auxiliary selected from the group comprising colouring agents, flavourings, sweeteners, plasticisers, taste-masking agents, emulsifiers, enhancers, humectants, preservatives and / or antioxidants.

14. A method for producing an oral thin film according to any one of claims 1 to 13, comprising the steps of: a) producing a solution, dispersion or melt containing at least the at least one matrix polymer and the at least one active pharmaceutical ingredient in the form of a mixture comprising the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt, wherein the mixture comprising the at least one active pharmaceutical ingredient both in the form of the free acid or base and in the form of a pharmaceutically acceptable salt contains the at least one active pharmaceutical ingredient in the form of the free acid or base and the at least one active pharmaceutical ingredient in the form of a pharmaceutically acceptable salt of the free acid or base in a molar ratio of 3:1 to 1:

3. b) spreading the solution, dispersion or melt from step a) in order to obtain a film, and c) drying the film step b) in order to obtain an oral thin film.

15. Use of the oral thin film according to any one of claims 1 to 13 or of a multilayer oral thin film obtainable by the method according to claim 14 as a medicament.