CA2506712A1

CA2506712A1 - Rapidly-decomposing administrable form for releasing ingredients in the oral cavity or in bodily cavities

Info

Publication number: CA2506712A1
Application number: CA002506712A
Authority: CA
Inventors: Christian Von Falkenhausen; Markus Krumme; Wolfgang Laux
Original assignee: Individual
Current assignee: LTS Lohmann Therapie Systeme AG
Priority date: 2000-07-04
Filing date: 2001-06-22
Publication date: 2003-01-06
Anticipated expiration: 2021-06-22
Also published as: CA2506712C

Abstract

A dosage form which is, in particular, sheet-like and rapidly disintegrating or soluble is as aqueous environment for rapid release of active ingredients in the oral cavity, in body orifices or is body cavities, where the dosage form comprises a matrix which comprises one or more water-soluble polymers as base substances, and comprises at least one active ingredient, is characterised is that the dosage form is provided with spaces or cavities which are present in the polymeric matrix and whose contents differ is terms of the state of aggregation from the matrix.

Claims

1. A dosage form, preferably a sheet-like dosage form, which is rapidly disintegrating or soluble in an aqueous environment, for rapid release of the active substance, nicotine, in the oral cavity, in body orifices or in body cavities, wherein the dosage form comprises a matrix which contains one or more water-soluble polymers as base substances and the active ingredient, nicotine, and wherein said dosage form is characterized in that it is provided with spaces or cavities which are present in the polymeric matrix and whose contents differ from the matrix in terms of the state of aggregation.

2. A dosage form as claimed in claim 1, characterized in that nicotine is present in the form of a salt, preferably as nicotine bitartrate.

3. A dosage form as claimed in claim 1 or 2, characterized in that said spaces or cavities are present in the matrix isolated from one another and preferably in the foam of bubbles.

4. A dosage form as claimed in claim 1 or 2, characterized in that said spaces or cavities are connected together, preferably forming a channel system penetrating through the matrix.

5. A dosage form as claimed in any one of claims 1 to 4, characterized in that said spaces or cavities are filled with a gas, gas mixture or preferably with air.

6. A dosage form as claimed in any one of claims 1 to 4, characterized in that said spaces or cavities are filled with a liquid or a liquid mixture, the liquid(s) being immiscible with the matrix material.

7. A dosage form as claimed in claim 6, characterized in that the liquid or the liquid mixture comprises one or more active ingredients.

8. A dosage form as claimed in any one of claims 1 to 7, characterized in that said spaces or cavities have a total volume, as a proportion of the total volume of the dosage form, of from 5 to 98%, preferably of 50 to 80%.

9. A dosage form as claimed in any one of claims 1 to 8, characterized in that said spaces or cavities of the dosage form are free of active ingredient in the state after production.

10. A dosage form as claimed in any one of the preceding claims, characterized in that the matrix of the dosage form represents a solidified foam.

11. A dosage form as claimed in any one of the preceding claims, characterized in that the surfaces of the dosage form have uneven or irregular shapes, preferably corrugated or relief-like.

12. A dosage form as claimed in any one of the preceding claims, characterized in that the polymer content of the matrix consists essentially of one or more synthetic or partially synthetic polymer(s) or natural biopolymers, which are film-forming and water-soluble, where the polymer(s) is/are preferably selected from the group which comprises cellulose derivatives, polyvinyl alcohol, polyacrylates and polyvinylpyrrolidone, with particularly preferred cellulose derivatives being hydroxypropylmethyl cellulose, hydroxymethylcellulose, carboxymethylcellulose, hydroxypropylcellulose and methylcellulose, and which additionally comprises water-soluble polysaccharides of vegetable or microbial origin, in particular pullulan, xanthan, alginates, dextrans, agar-agar, pectins and carrageenan, and proteins, preferably gelatin, caseinates or other gel-forming proteins or protein hydrolysates.

13. A dosage form as claimed in any one of the preceding claims, characterized in that it is preferably in the form of a wafer, with the thickness of the dosage form preferably being between 50 µm and 5 mm, particularly preferably between 0.5 and 1 mm.

14. A dosage form as claimed in any one of the preceding claims, characterized in that the matrix and/or said spaces or cavities comprise excipients or additives, preferably excipients or additives selected from the group consisting of surfactants, gas-forming substances, moisturizers or humectants and substances that improve the stability of the foam.

15. A process for the production of a sheet-like oral dosage form which is rapidly disintegrating or soluble in an aqueous environment, for rapid release of the active ingredient, nicotine, in the oral cavity, in body orifices or in body cavities, wherein the dosage form comprises a matrix which contains one or more polymers as base substances, and further contains the active ingredient, nicotine, and wherein the dosage form is provided with spaces or cavities which are present in the polymeric matrix and whose contents differ from the matrix in terms of the state of aggregation, said process being characterized by the following operational steps:
a) preparation of a solution or dispersion which comprises at least one water-soluble film-forming polymer and the active ingredient, nicotine;
b) foaming of the solution or dispersion by introducing gas or gas mixture or by chemical production of gas or by decompression of a dissolved gas, where appropriate after previous addition of a foam-stabilizing agent;
c) spreading of this solution or dispersion on a coating substrate;
d) solidification of the cavity-containing film by drying and removal of the solvent

16. A process for the production of a sheet-like oral dosage form which is rapidly disintegrating or soluble in an aqueous environment, for rapid release of the active ingredient, nicotine, in the oral cavity, in body orifices or in body cavities, wherein the dosage form comprises a matrix which contains one or more polymers as base substances, and further contains the active ingredient, nicotine, and where the dosage form is provided with spaces or cavities which are present in the polymeric matrix and whose contents differ from the matrix in terms of the state of aggregation, said process being characterized by the following operational steps:
a) preparation of a solution or dispersion which comprises at least one water-soluble film-forming polymer and the active ingredient, nicotine;
b) addition of hydrophobic solvent which is immiscible with the solvent used to prepare said solution or dispersion, and preparation of an emulsion which contains the hydrophobic solvent in the form of finely dispersed droplets;

c) spreading of this solution or dispersion on a coating substrate;
d) solidification of the film with formation of cavities by drying and removal of the solvent.

17. A process for the production of a sheet-like oral dosage form which is rapidly disintegrating or soluble in an aqueous environment, for rapid release of the active ingredient, nicotine, in the oral cavity, in body orifices or in body cavities, wherein the dosage form comprises a matrix which contains one or more polymers as base substances, and further contains the active ingredient, nicotine, and wherein the dosage foam is provided with spaces or cavities which are present in the polymeric matrix and whose contents differ from the matrix in terms of the state of aggregation, said process being characterized by the following operational steps:
a) preparation of a solution or dispersion which comprises at least one water-soluble film-forming polymer and the active ingredient, nicotine;
b) addition of an excipient or a combination of excipients capable of gas formation;
c) spreading of this solution or dispersion on a coating substrate;
d) solidification of the film with formation of cavities by drying and removal of the solvent.

18. A process for the production of a sheet-like oral dosage form which is rapidly disintegrating or soluble in an aqueous environment, for rapid release of the active ingredient, nicotine, in the oral cavity, in body orifices or in body cavities, wherein the dosage form comprises a matrix which contains one or more polymers as base substances, and further contains the active ingredient, nicotine, and wherein the dosage form is provided with spaces or cavities which are present in the polymeric matrix and whose contents differ from the matrix in terms of the state of aggregation, said process being characterized by the following operational steps:
a) preparation of a polymer-containing melt (hot melt) which comprises at least one water-soluble film-forming polymer and said active ingredient, nicotine;

b) foaming of the melt by introducing gas or gas mixture or by chemical production of gas or by decompression of a dissolved gas, where appropriate after previous addition of a foam-stabilizing agent;
c) spreading of the melt on a coating substrate;
d) solidification of the film by cooling.

19. The process as claimed in any of claims 15 to 18, characterized in that steps c) and d) are replaced or modified by following steps c) and d);
c) production of the polymer matrix in the form of a block, starting from the solution or dispersion or from the melt;
d) cutting of the solidified block in order to obtain sheet-like forms.

20. The process as claimed in any of claims 15 to 19, characterized in that nicotine is added in the form of a salt, preferably as nicotine bitartrate.

21. The use of a dosage form as claimed in one or more of claims 1 to 14 or of a process product from one of the processes as claimed in claims 15 to 20 for administration of nicotine in the oral cavity.

22. The use of a dosage form as claimed in one or more of claims 1 to 14 or of a process product from one of the processes as claimed in claims 15 to 20 for rectal, vaginal or intranasal administration of nicotine to humans or animals.