ORAL THIN FILM

Abstract

The present invention relates to an oral thin film comprising at least one polymer and at least one pharmaceutically active agent, wherein the concentration of the at least one pharmaceutically active agent in the oral thin film is greater than the saturation concentration of the at least one pharmaceutically active agent in the oral thin film, and wherein the oral thin film comprises at least one material which serves as crystal nucleus for the at least one pharmaceutically active agent, to a method for producing said oral thin film, and to the use of said oral thin film as a medicament.

Claims

1. An oral thin film comprising at least one polymer and at least one pharmaceutically active agent, wherein the concentration of the at least one pharmaceutically active agent in the oral thin film is greater than the saturation concentration of the at least one pharmaceutically active agent in the oral thin film, characterised in that the oral thin film comprises at least one material which serves as crystal nucleus for the at least one pharmaceutically active agent.

2. The oral thin film according to claim 1, characterised in that the material which serves as crystal nucleus for the at least one pharmaceutically active agent is contained in the oral thin film in an amount of 0.01 to 20 wt. % in relation to the total weight of the oral thin film.

3. The oral thin film according to claim 1, characterised in that the material which serves as crystal nucleus for the at least one pharmaceutically active agent comprises amorphous, pyrogenic silicon dioxide.

4. The oral thin film according to claim 1, characterised in that the at least one polymer comprises a water-soluble and/or water-swellable polymer.

5. The oral thin film according to claim 1, characterised in that the at least one polymer is selected from the group consisting of starch and starch derivatives, dextrans, cellulose derivatives, such as carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl ethyl cellulose, sodium carboxymethyl cellulose, ethyl or propyl cellulose, polyacrylic acids, polyacrylates, polyvinylpyrrolidones, polyvinyl alcohols, polyethylene oxide polymers, polyacrylamides, polyethylene glycols, gelatines, collagen, alginates, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan, natural gums, and mixtures thereof.

6. The oral thin film according to claim 1, characterised in that the at least one polymer is contained in the oral thin film in an amount of 30 to 80 wt. % in relation to the total weight of the oral thin film.

7. The oral thin film according to claim 1, characterised in that the pharmaceutically active agent is selected from the group consisting of hypnotics, sedatives, antiepiletics, analeptics, psychoneurotropic drugs, neuro-muscle blockers, antspasmodics, antihistamines, antiallergics, cardiotonics, antiarrhythmics, diuretics, hypotensives, vasopressors, antidepressants, antitussives, expectorants, thyroid hormones, sexual hormones, antidiabetics, antitumour active agents, antibiotics, chemotherapeutics and narcotics.

8. The oral thin film according to claim 1, characterised in that the at least one pharmaceutically active agent comprises ketamine or a pharmaceutically acceptable salt thereof.

9. The oral thin film according to claim 1, characterised in that the oral thin film further comprises at least one auxiliary selected from the group comprising colouring agents, flavourings, sweeteners, taste-masking agents, emulsifiers, enhancers, pH regulators, humectants, preservatives and/or antioxidants.

10. A method for producing an oral thin film according to claim 1, comprising the steps of: a) producing a suspension or solution, comprising the at least one polymer, the at least one pharmaceutically active agent and the material which serves as crystal nucleus for the at least one pharmaceutically active agent, and b) spreading and drying the suspension or solution obtained in step a) in order to obtain a thin film.

11. The method according to claim 10, wherein the at least one pharmaceutically active agent in step a) is present substantially completely dissolved.

12. The method according to claim 10, wherein the at least one pharmaceutically active agent, during the drying in step b), crystallises until below the saturation limit.

13. An oral thin film obtainable by the method according to claim 10.

14. A method for delivering hypnotics, sedatives, antiepiletics, analeptics, psychoneurotropic drugs, neuro-muscle blockers, antspasmodics, antihistamines, antiallergics, cardiotonics, antiarrhythmics, diuretics, hypotensives, vasopressors, antidepressants, antitussives, expectorants, thyroid hormones, sexual hormones, antidiabetics, antitumour active agents, antibiotics, chemotherapeutics or narcotics to a patient, comprising administering an effective amount of a pharmaceutically active agent using the oral thin film according to claim 1.

15. The oral thin film according to claim 1, characterised in that the at least one pharmaceutically active agent comprises (S) ketamine or a pharmaceutically acceptable salt thereof.

16. A method for producing an oral thin film according to claim 1, comprising the steps of: a) producing a suspension or solution, comprising the at least one polymer, the at least one pharmaceutically active agent and the material which serves as crystal nucleus for the at least one pharmaceutically active agent, and b) spreading and drying the suspension or solution obtained in step a) in order to obtain a thin film with a mass per unit area of approximately 50 to 300 g/m.sup.2.

Description

DESCRIPTION OF THE DRAWINGS

[0048] FIG. 1 shows a thin film according to the invention in accordance with the formulation specified in Table 1, directly after the drying.

[0049] FIG. 2 shows a thin film according to the comparative example specified in Table 1, after the drying.

[0050] The invention will be described in greater detail hereinafter on the basis of non-limiting examples.

EXAMPLES

Example 1

[0051]

TABLE-US-00001 Proportion [wt. %] Comparative Ingredient Function example (S) ketamine Active agent 41.0 41.0 HPMC 603 Polymer 39.0 39.5 (3 mPas).sup.1 HPMC 60SH50 Polymer 10.0 10.0 (50 mPas).sup.1 Glycerol Humectant 3.5 3.5 Sucralose Taste corrector 1.0 1.0 Saccharin Na Taste corrector 2.0 2.0 Cherry Flavour EU Taste corrector 3.0 3.0 Aerosil 200.sup.2 Crystal nucleus 0.5 — Water Residual moisture 8 8 .sup.1Hydroxypropyl methylcelluloses with different viscosities, wherein these have a viscosity of approximately 3 or approximately 50 mPas (measured by USP monograph <911> method 1, from 2012). .sup.2Pyrogenic amorphous SiO.sub.2 from Evonik.

[0052] The oral thin film according to the invention has a homogeneous appearance. The active agent is present in crystalline form, homogeneously distributed, in the oral thin film (see FIG. 1).

[0053] The oral thin film according to the formulation of the comparative example has an extremely inhomogeneous appearance. The active agent is inhomogeneously crystallised so that the oral thin film has many fracture lines (see FIG. 2).