CA2259353C - Plaster for the transdermal application of pergolide - Google Patents
Plaster for the transdermal application of pergolide Download PDFInfo
- Publication number
- CA2259353C CA2259353C CA002259353A CA2259353A CA2259353C CA 2259353 C CA2259353 C CA 2259353C CA 002259353 A CA002259353 A CA 002259353A CA 2259353 A CA2259353 A CA 2259353A CA 2259353 C CA2259353 C CA 2259353C
- Authority
- CA
- Canada
- Prior art keywords
- transdermal therapeutic
- therapeutic system
- pergolid
- group
- layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
Abstract
The invention relates to a patch for transdermal application of pergolid and its pharmaceutically acceptable salts.
Description
Plaster for Transdezmal Application of Peraolide The invention relates to a patch or plaster for transdermal application of pergolid and its pharmaceutically harmJ.ess salts.
Fergolid (D~6-n--propyl-8~i-methylmercaptomethylexgoline) is a dopamine receQtor coenzyme and is administered among other t.hir~.gs as an anti-parkinsaa ageat (8P-A 0 003 6671 , for the treatment of addiction caused by psycho-st~.mulants (EP-A 0 204 954), and for niCOtirxe addiction (GB~A 2 204 240) .
Various orally admixiist.ered formulations Qf pergolid are kriowri from EP-A 0 003 667 and fiP-A 0 527 835. The therapeutically effective daily dose. is 0.01 to 2o mg.
Generally it cari be said that the biological activity pf drugs administered orally or intravenously is often unsatisfactory. 'fhe hepatic metabolism of the drug upon the first passage through the liver can lead to undesired concentrations and td~ciC by-praduCts, or to the loss of ox reduction of effect. Compared to oral administration, the transdermal administration of drugs or agents has various advantages. The drug supply can be better controlled over a longer time interval, whereby significant blood plasma fluctuation is avoided. In addition, the required therapeutic dosage cata usually be distinctly reduced.
Fuzthermore, a patch is often more preferred by the patient than one or more tablets to be taken daily.
rn oral application, pergolid has a low bio-activity.
Consequently, it is difficult to achieve a cor~.stant blood plasma level over a longer time period, so that three doses daily are required.
The object of the present invention is to provide a transdermal system for the systematic application of pergolid or one of ita pharmaceutically harmless salts where the drawbacks of oral administration forms are avoided.
The object underlying the invention is now solved with a 1o transdermal therapeutic system with an amount of pexgolid or one of its pharmaceutically harmless salts.
The agent pergolid can be applied as a free pergolid base, pergolid mesylate and/or pergolid hydrochloride.
pergolid oz one of its pharmaceutically acceptable salts as the active agent can also be used in combination with one or more further known substances, particularly in two-cold or three-fold combinations. These further known agents can 2o modify, enhance, synergize or alter the potency of the pezgolid effect. For example, dopamine coenzymes can be provided.
Particularly suitable further agents include levodopa, z5 carbidopa, selegeline, tracrine, physostingu~ine, galanthamirie, 1-hydroxytacrine and/or chemical derivatives thereof, metabolites thereof and/or pharmaceutically acceptable salts thereof.
3o Suitable permeation promoters include singly and/or multi-valent aliphatic, cycloaliphatic and/or aromatic-aliphatic alcohols with up to 8 C atoms, for example ethanol, 12-propandiol, dexpanthenol and/or polyethylene glycol;
alcohol/water mixtures; saturated and/or unsaturated fatty 35 alcohols with 8 to 18 carbon atoms: saturated and/or unsaturated tatty acids with 8 to 18 carbon atoms; their esters; natural vitamin E; synthetic vitamin E; and/or vitamin E derivatives.
Since pergolid is light-sensitive to a certain extent, stabili2ers can be employed, for example as is known from US-A 5 114 948 or EP-g 0 314 387. Examples include polyvinylpyrrolidone, alpha-tocopherolsuccinate, propylgallate, methionine, cysteine and/or cysteine xo hydrochloride_ The transdermal therapeutic system according to the invention can be a patch, particularly with an impermeable cover layer and removable protection layer, especially a matrix system or 1S a membrane system.
The cover layer can be polyester, polypropylene, polyethylene or polyurethane, optionally provided with a metallisation or pigment. The removeable protection layer can be polyester, 2o polypropylene or paper with a silicone and/or polyethylene coating.
The transdermal therapeutic system according to the invention may be a matrix patch With - an impermeable cover layer - a drug-containing self-adhesive matrix layer or a drug-containing matrix layer Nhich iS coated with an adhesive, -- a removeable protection layer and - pergolid or one of its pharmaceutically acceptable salts as the active agent (drug), - optionally with further active agents and/or permeation promoters and/or stabilisers.
The matrix can be based on polyacrylate, silicone, polyisobutylene, butyl rubber, styrene/butadiene copolymer or styrene/isoprene copolymer. Such matrix materials common in the medical field are knot~m in the priox art. Examples of acrylate adhesives include DuroTak adhesives, A further enubodiment of the invention relates to a membrane system including - an impermeable cover layer, - a drug-containing reservoir or a drug-containing reservoir layer, - a semi-permeable membrane, - s facultative adhesive layer, - a removeable protection layer and is - pergolid or one of its pharmaceutically acceptable salts, - optionally, further active agents and/or permeation promoters, stabilisers, emulsifying agents, thickening agents and/or common membrane system or reservoir patch additives.
The drug-containing reservoir layer can thus be provided in an intermediate space formed between the covering layer and the membrane. The reservoir is filled with the active agents (drug) and facultative additives.
zs Inert polymers are suitable for the membrane, particularly on the basis of polypropylene, polyvinylacetate or silicone.
when a membrane is provided, it can have the effect of so controlling drug re~.ease depending on the pore size.
In the following, the invention is illustrated through examples.
Example 1 (Matrix patch) The following components are dispersed in a sufficient amount s of ethyl acetate:
pergolid g natural vitamin E 10 g propylene glycol 15 g io acrylate adhesive 65 g (as 35 ~ solution in ethyl acetate e.g. DuroTak 326-1753) In a commercial coating machine, the obtained dispersion is 1s applied to a silicone-treated polypropylene foil, which results in a surface Height of the dried drug-containing adhesive matrix of 100 g/m2. In a coating station, a 50 ),un thick polyurethane foil is applied. Thereafter, 20 cmz or optionally 10, 30, 90 or 50 cm' patches are stamped out of ao the laminate.
Example 2 (Reservoir TTS) 25 The following components are dispersed in ethanol/water;
pergolid (or a corresponding amount of pergolid salt, e.g. pergolid mesylate) 5 to 10 ~
optionally, natural vitamin E and/or so polyvinylpyrrolidone as stabiliser.
For the production of the patches, the following elements are Loreseen:
35 covering lay~sr of for example polyethylene semi-permeable membrane, e.g. CoTan~ 9711 adhesive for adhesive layer, e.g. Duro-TakTM 326-1753 removeable protection layer, e.g. GelroflexTM.
In a first step, a laminate is produced in a common machine with the adhesive, the membrane and the protection layer. In a second step, an empty TTS is produced from the laminate and the covering layer. In a third step, the empty TTS is filled with the active agent dispersion. In a fourth step, the filled TTS is closed and in a fifth step patches are stamped out in the desired size.
Fergolid (D~6-n--propyl-8~i-methylmercaptomethylexgoline) is a dopamine receQtor coenzyme and is administered among other t.hir~.gs as an anti-parkinsaa ageat (8P-A 0 003 6671 , for the treatment of addiction caused by psycho-st~.mulants (EP-A 0 204 954), and for niCOtirxe addiction (GB~A 2 204 240) .
Various orally admixiist.ered formulations Qf pergolid are kriowri from EP-A 0 003 667 and fiP-A 0 527 835. The therapeutically effective daily dose. is 0.01 to 2o mg.
Generally it cari be said that the biological activity pf drugs administered orally or intravenously is often unsatisfactory. 'fhe hepatic metabolism of the drug upon the first passage through the liver can lead to undesired concentrations and td~ciC by-praduCts, or to the loss of ox reduction of effect. Compared to oral administration, the transdermal administration of drugs or agents has various advantages. The drug supply can be better controlled over a longer time interval, whereby significant blood plasma fluctuation is avoided. In addition, the required therapeutic dosage cata usually be distinctly reduced.
Fuzthermore, a patch is often more preferred by the patient than one or more tablets to be taken daily.
rn oral application, pergolid has a low bio-activity.
Consequently, it is difficult to achieve a cor~.stant blood plasma level over a longer time period, so that three doses daily are required.
The object of the present invention is to provide a transdermal system for the systematic application of pergolid or one of ita pharmaceutically harmless salts where the drawbacks of oral administration forms are avoided.
The object underlying the invention is now solved with a 1o transdermal therapeutic system with an amount of pexgolid or one of its pharmaceutically harmless salts.
The agent pergolid can be applied as a free pergolid base, pergolid mesylate and/or pergolid hydrochloride.
pergolid oz one of its pharmaceutically acceptable salts as the active agent can also be used in combination with one or more further known substances, particularly in two-cold or three-fold combinations. These further known agents can 2o modify, enhance, synergize or alter the potency of the pezgolid effect. For example, dopamine coenzymes can be provided.
Particularly suitable further agents include levodopa, z5 carbidopa, selegeline, tracrine, physostingu~ine, galanthamirie, 1-hydroxytacrine and/or chemical derivatives thereof, metabolites thereof and/or pharmaceutically acceptable salts thereof.
3o Suitable permeation promoters include singly and/or multi-valent aliphatic, cycloaliphatic and/or aromatic-aliphatic alcohols with up to 8 C atoms, for example ethanol, 12-propandiol, dexpanthenol and/or polyethylene glycol;
alcohol/water mixtures; saturated and/or unsaturated fatty 35 alcohols with 8 to 18 carbon atoms: saturated and/or unsaturated tatty acids with 8 to 18 carbon atoms; their esters; natural vitamin E; synthetic vitamin E; and/or vitamin E derivatives.
Since pergolid is light-sensitive to a certain extent, stabili2ers can be employed, for example as is known from US-A 5 114 948 or EP-g 0 314 387. Examples include polyvinylpyrrolidone, alpha-tocopherolsuccinate, propylgallate, methionine, cysteine and/or cysteine xo hydrochloride_ The transdermal therapeutic system according to the invention can be a patch, particularly with an impermeable cover layer and removable protection layer, especially a matrix system or 1S a membrane system.
The cover layer can be polyester, polypropylene, polyethylene or polyurethane, optionally provided with a metallisation or pigment. The removeable protection layer can be polyester, 2o polypropylene or paper with a silicone and/or polyethylene coating.
The transdermal therapeutic system according to the invention may be a matrix patch With - an impermeable cover layer - a drug-containing self-adhesive matrix layer or a drug-containing matrix layer Nhich iS coated with an adhesive, -- a removeable protection layer and - pergolid or one of its pharmaceutically acceptable salts as the active agent (drug), - optionally with further active agents and/or permeation promoters and/or stabilisers.
The matrix can be based on polyacrylate, silicone, polyisobutylene, butyl rubber, styrene/butadiene copolymer or styrene/isoprene copolymer. Such matrix materials common in the medical field are knot~m in the priox art. Examples of acrylate adhesives include DuroTak adhesives, A further enubodiment of the invention relates to a membrane system including - an impermeable cover layer, - a drug-containing reservoir or a drug-containing reservoir layer, - a semi-permeable membrane, - s facultative adhesive layer, - a removeable protection layer and is - pergolid or one of its pharmaceutically acceptable salts, - optionally, further active agents and/or permeation promoters, stabilisers, emulsifying agents, thickening agents and/or common membrane system or reservoir patch additives.
The drug-containing reservoir layer can thus be provided in an intermediate space formed between the covering layer and the membrane. The reservoir is filled with the active agents (drug) and facultative additives.
zs Inert polymers are suitable for the membrane, particularly on the basis of polypropylene, polyvinylacetate or silicone.
when a membrane is provided, it can have the effect of so controlling drug re~.ease depending on the pore size.
In the following, the invention is illustrated through examples.
Example 1 (Matrix patch) The following components are dispersed in a sufficient amount s of ethyl acetate:
pergolid g natural vitamin E 10 g propylene glycol 15 g io acrylate adhesive 65 g (as 35 ~ solution in ethyl acetate e.g. DuroTak 326-1753) In a commercial coating machine, the obtained dispersion is 1s applied to a silicone-treated polypropylene foil, which results in a surface Height of the dried drug-containing adhesive matrix of 100 g/m2. In a coating station, a 50 ),un thick polyurethane foil is applied. Thereafter, 20 cmz or optionally 10, 30, 90 or 50 cm' patches are stamped out of ao the laminate.
Example 2 (Reservoir TTS) 25 The following components are dispersed in ethanol/water;
pergolid (or a corresponding amount of pergolid salt, e.g. pergolid mesylate) 5 to 10 ~
optionally, natural vitamin E and/or so polyvinylpyrrolidone as stabiliser.
For the production of the patches, the following elements are Loreseen:
35 covering lay~sr of for example polyethylene semi-permeable membrane, e.g. CoTan~ 9711 adhesive for adhesive layer, e.g. Duro-TakTM 326-1753 removeable protection layer, e.g. GelroflexTM.
In a first step, a laminate is produced in a common machine with the adhesive, the membrane and the protection layer. In a second step, an empty TTS is produced from the laminate and the covering layer. In a third step, the empty TTS is filled with the active agent dispersion. In a fourth step, the filled TTS is closed and in a fifth step patches are stamped out in the desired size.
Claims (20)
1. A transdermal therapeutic system comprising an amount of pergolid as the active agent or one of its therapeutically acceptable salts and a permeation promoter selects ed from the group consisting of natural vitamin E, synthetic vitamin E, a vitamin E derivative and combinations thereof.
2. The transdermal therapeutic system of Claim l, characterized in that the pergolid is selected from the group consisting of a free pergolid base, pergolid mesylate, pergolid hydrochloride and combinations thereof.
3. The transdermal therapeutic system of Claim 1 or 2, further comprising at least one other dopamine coenzyme as further common active agent.
4. The transdermal therapeutic system of Claim 3, characterized by pergolid or one of its pharmaceutically acceptable salts as active agent in two-fold or three-fold con.bination with other dopamine coenzymes.
5. The transdermal therapeutic system of Claim 3 of 4, characterized by a further active agent selected from the group consisting of levodopa, cardidopa, selegeline, tacrine, physostigmine, galanthamine, 1-hydroxytacrine, their metabolites and their pharmaceutically acceptable salts.
6. The transdermal therapeutic system according to any one of Claims 1 to 5, further comprising a further permeation promoter selected from the group consisting of an aliphatic, a cycloaliphatic and an aromatic-aliphatic alcohol, which alcohols are single or multi-valent and have up to 8 C atoms, an alcohol-water mixture, a saturated or unsaturated fatty alcohol with 8 to 18 C atoms, and a saturated or unsaturated fatty acid with 8 to 18 C atoms or an ester of these fatty acids, and mixtures thereof.
7. The transdermal therapeutic system according to Claim 6, further comprising a further permeation promoter selected from the group consisting of ethanol, 1,2-propandiol, dexpanthenol, polyethylene glycol and mixtures thereof as the further permeation promoter.
8. The transdermal therapeutic system of any one of Claims 1 to 7, further comprising a known stabiliser.
9. The transdermal therapeutic system of any one of Claims 1 to 8, in the form of a patch with an impermeable cover layer and a removeable protection layer.
10. The transdermal therapeutic system according to Claim 9, wherein the system is a matrix system or a membrane system.
11. The transdermal therapeutic system of Claim 9 or 10, characterized in that the cover layer is comprised of polyester, polypropylene, polyethylene or polyurethane, optionally being metallized or provided with pigments.
12. The transdermal therapeutic system of Claim 9, 10, or 11, characterized in that the removeable protection layer is comprised of polyester, polypropylene or paper with a silicone or polyethylene coating.
13. The transdermal therapeutic system of Claim 9, 10, 11, or 12, comprising of a matrix system comprising:
- an impermeable cover layer, an agent-containing self-adhesive matrix layer or an agent-containing matrix layer coated with an adhesive, - removeable protection layer, and - pergolid or one of its pharmaceutically acceptable salts as the active agent.
- an impermeable cover layer, an agent-containing self-adhesive matrix layer or an agent-containing matrix layer coated with an adhesive, - removeable protection layer, and - pergolid or one of its pharmaceutically acceptable salts as the active agent.
14. The transdermal therapeutic system of Claim 13, characterized in that the matrix layer is comprised of polyacrylate, silicone, polyisobutylene, butyl rubber, styrene/butadiene copolymer or styrene/isoprene copolymer.
15. The transdermal therapeutic system of Claim 9, 10, 11, or 12, comprising a membrane system comprising:
- an impermeable cover layer, - an agent-containing reservoir or an agent-containing reservoir layer, - a microporous or semi-permeable membrane, - a faculative adhesive layer, - a removeable protection layer and - pergolid or one of its pharmaceutically acceptable salts as the active agent.
- an impermeable cover layer, - an agent-containing reservoir or an agent-containing reservoir layer, - a microporous or semi-permeable membrane, - a faculative adhesive layer, - a removeable protection layer and - pergolid or one of its pharmaceutically acceptable salts as the active agent.
16. The transdermal therapeutic system of Claim 15, further comprising a component selected from the group consisting of known emulsifying agents, known thickening agents, known membrane system additives and mixtures thereof.
17. The transdermal therapeutic system of Claim 15 or 16, characterized in that the microporous or semi-permeable membrane is comprised of an inert polymer.
18. The transdermal therapeutic system of Claim 8 wherein the known stabiliser is selected from the group consisting of polyvinylpyrrolidone, alpha-tocpherolsuccinate, propylgallate, methionine, cysteine, cysteine hydrochloride and combinations thereof.
19. The transdermal therapeutic system of Claim 17 wherein the inert polymer is selected from the group consisting of polypropylene, polyvinyl acetate and silicone.
20. The transdermal therapeutic system of Claim 17 wherein the inert polymer is comprised of polypropylene, polyvinyl acetate or silicone.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19626621.1 | 1996-07-02 | ||
| DE19626621A DE19626621A1 (en) | 1996-07-02 | 1996-07-02 | Plaster for transdermal application of pergolide |
| PCT/EP1997/003458 WO1998000142A1 (en) | 1996-07-02 | 1997-07-02 | Plaster for the transdermal application of pergolide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2259353A1 CA2259353A1 (en) | 1998-01-08 |
| CA2259353C true CA2259353C (en) | 2006-09-05 |
Family
ID=36968407
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002259353A Expired - Fee Related CA2259353C (en) | 1996-07-02 | 1997-07-02 | Plaster for the transdermal application of pergolide |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2259353C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19821788C1 (en) * | 1998-05-15 | 1999-12-02 | Sanol Arznei Schwarz Gmbh | Transdermal therapeutic system (TTS) containing pergolide |
-
1997
- 1997-07-02 CA CA002259353A patent/CA2259353C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2259353A1 (en) | 1998-01-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |