CA2274893A1 - Active substance carrier for releasing apomorphine into the buccal cavity - Google Patents

Active substance carrier for releasing apomorphine into the buccal cavity Download PDF

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Publication number
CA2274893A1
CA2274893A1 CA002274893A CA2274893A CA2274893A1 CA 2274893 A1 CA2274893 A1 CA 2274893A1 CA 002274893 A CA002274893 A CA 002274893A CA 2274893 A CA2274893 A CA 2274893A CA 2274893 A1 CA2274893 A1 CA 2274893A1
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CA
Canada
Prior art keywords
active substance
pharmaceutical preparation
apomorphine
preparation according
administration
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.)
Abandoned
Application number
CA002274893A
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French (fr)
Inventor
Karsten Cremer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LTS Lohmann Therapie Systeme AG
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2274893A1 publication Critical patent/CA2274893A1/en
Abandoned legal-status Critical Current

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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
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Psychology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention concerns a medicament preparation with a flat, foil-, paper- or wafer-like presentation for the application and release of active substances into the buccal cavity. The preparation is characterized in that it contains apomorphine or one of its therapeutically suitable salts.

Description

'E
r Active substance carrier for the release of apomorphine in the oral cavity The present invention relates to a pharmaceutical prepa-ration for application of active substances in the region of the oral cavity or oral mucosa. In particular, it relates to a preparation which is adapted to be flat and in the form of a foil-, paper- or wafer-shaped administration form.
Flat active substance carriers have already been developed and produced, for various purposes. DE-OS 27 46 414 can be regarded as fundamental to this administration form, said document describing a foil-type tape of active substance, binder and further active substances, with a direct relation existing, by reason of the homogeneous thickness and density, between a unit of length of the tape and the dose of active substance contained therein. The advantages of the continuous dosage property have been recognized also by other applicants and have been described in specific individual variants. Thus, DE-PS 36 30 603 claims a flat-shaped carrier material, for example in the form of a separating layer, having an active substance-containing coating, the latter having to be peeled off the carrier material after having been previously separated into dosage units.
The practicality of the flat format in general as well as the advantages afforded by the production of this administration form and by the dosage employing said administration form have been recognized a.n the prior art.
Further advantages can be derived such as the fact that, relative to the weight of the administration form, a relatively large surface may be printed on the said i administration form, thus increasing intake safety as wall as affording the possibility of discrete intake without any liguid being available.
If an active substance is to be applied that can be brought to absorption via the oral mucosa, a flat, film- or paper-like active substance carrier enables a more rapid onset of action than in the case of application of conventional administration forms, such as tablets. Tablets are typically adapted for active substance release in the gastrointestinal tract after swallowing. Usual, rapidly disintegrating tablets release active substance in the stomach, with the disintegration of the administration form being a precondition for the active substance release.
Freguently, the disintegration of a tablet in the liquids contained in the gastrointestinal tract is a mufti-stage process. If the tablet has a coat, this must first disintegrate in order to expose the pressed piece. This is followed by so-called primary disintegration, during which the tablet disintegrates into small fragments, e.g. into the granules from which it was pressed, said fragments in turn disintegrating during the so-called secondary disintegration into the powders they are composed of.
Whereas the primary disintegration is macroscopically visible, and according to the pharmacopoeia is tested employing a special apparatus, secondary disintegration is hardly perceptible or measurable, although it is a direct prerequisite of the dissolution of active ingredient. It follows that even if usual tablets are retained in the mouth until they are macroscopically disintegrated, this does not necessarily mean that they have already released the active substances contained therein, whereas flat, film- or paper-like active substance carriers are capable of doing so within a few seconds, up to minutes, after application thereof. Insofar, the latter are better suitable than tablets for introducing active substances r more quickly into the organism, and they can be advantageously used where a rapid onset of action is required or desirable, thus, for example, in the administration of analgesics, antiallergics, antitussives, antiemetiCS, active substances against angina pectoris, migraine, hypotension or hypotonia, etc.
Despite these obvious advantages, such flat administration forms have hitherto hardly been successful. Obviously, the advantage as compared to conventional administration forms does not suffice for many manufacturers of pharmaceutics to develop products of this type comprising the usual active ingredients and to pursue the legal drug approval thereof, which involves considerable effort and high costs.
Moreover, existing production machinery and existing know-how cannot be used for these novel products; this means that the necessity of large investments would arise.
Despite the above-described advantages of flat; film- or paper-like administration forms, the therapeutic and/or economic advantage over conventional tablets in adminis-tration of common active substances which are also perorally applicable is not great enough to justify the costs of switching over to these administration forms.
It is thus the object of the present invention to create a pharmaceutical preparation on the basis of, and having the general advantages of, flat, film- or paper-like active substance carriers, which pharmaceutical preparation, however, affords, apart from the above advantages, additional economical and/or therapeutical advantages over pharmaceutical preparations of the same active substance which are based on conventional administration forms such as tablets, due to the combination with a special active substance.
The object is solved in accordance with Claim 1 by providing a pharmaceutical preparation on the basis of a flat, foil-, paper- or wafer-like active substance carrier and containing as active substance apomorphine or one of its therapeutically acceptable salts.
As Will be explained in the following, an administration form according to Claim 1 is by far superior to a conventional oral administration form for administeriag apomorphine - both from the econamical as well as the therapeutical point of view; it is especially suitable for the therapy of Parkinson's disease.
Part of the symptoms and signs of Parkinson's disease is fluctuating dyskinesia, which is hardly accessible to pharmacotherapy and which is known under the term of "on-off phenomenon". This is the sudden change between good ability and akinesia. The active agent apomorphine, a potent dopamiae agonist, is suitable for acute therapy of the "off phases". However, for this purpose, apomorphine must be injected subcutaneously since it is hardly bioavailable after peroral administration, that is it appears in the blood circulation only to the very small extent of a few percent of the dose taken. Presumably, the reason for the lack in bioavailability lies in the extensive decomposition of the substance during the first liver passage following gastrointestinal absorption ("first-pass effect").
A possibility of avoiding the first-pass effect in oral administration is to bring the active substance to absorption already on the oral mucosa. In order to enter the central systemic circulation, an active substance which enters into the blood via the oral mucosa does not have to first pass the portal system and thus, in concentrated form, the liver, which metabolizes the active substance. A

prerequisite for buccal or sublingual application, however, is a sufficient permeability of the oral mucosa to the active substance, taking into consideration the required dose. Permeability in turn depends to a large extent on the physicochemical properties of the active substance. Buccal or sublingual administration of apomorphine appears to be very much desirable, due to the fact that injections of the patient are thereby avoided.
In recent years several research groups have therefore attempted to apply apomorphine via the oral mucosa. In fact, it has been possible to detect a relevant absolute bioavailability after sublingual administration in several e~eriments carried out independently from each other, as, for example, by Gancher et al. (Movement Disorders 6 [1991], pages 212-215), who found values of bioavailability between 10 and 22%. Montastruc et al. (Clin.Neuropharmacol.
14 [1991], pages 432 - 437) showed the equivalents of 30 mg of apomorphine sublingually, to 3 mg of the active substance subcutaneously. Similar results are found in Hughes et al. (Clin.Neuropharmacol. 14 [1991], pages 556-561), Durif et al. (Eur.J.Clin.Pharmaco1.41 [1991], pages 493 - 494), and others.
It is to be criticized, however, that nowhere in the methodic portion of the publications of these studies have the parameters of the sublingual application themselves been defined. The only indications a.n this respect are made by Gancher et al., who instruct the test persons to keep the apomorphine tablets of 6 mg each under their tongue until they are dissolved. Where the tablets had not disintegrated after 5 minutes, the test persons were allowed to take a small drink of water, but not to swallow this. In the other applications it was obviously riot ensured at all that either a portion of the active substance dose that was as great as possible or at least a portion that came as near to being equally large as possible was available to the oral mucosa for absorption from the administration form. At least the duration of action, however, should be selected so as to be sufficient and constant, and swallowing of saliva should be eliminated over a constant period of time in order to methodically limit sublingual application against a peroral one.
Moreover, the administration form administered is all of the above mentioned cases, gamely a peroral tablet, is to be regarded, as has already been stated, as totally unsuitable for sublingual application. Presumably, it was precisely this problem which caused the high variability observed in the above mentioned studies.
This is completely different for the application of apo-morphine by-means of an administration form according to Claim 1. This administration form can be brought into direct contact with the oral mucosa. Due to the flat shape, immediately after application about half of the surface of the administration form, which is large any way, is located directly on the mucosa. The apomorphine released thus encounters two factors particularly favourable for entry into the body, namely a short diffusion path and a large diffusion area. This dianinishes the portion of apomorphine that is swallowed, which in the case of other active agents would not be a particular problem. However, with apo-morphine, swallowing of the active substance should be avoided if possible, or to be reduced since for the above mentioned reasons swallowed apomorphine is ineffective.
Even in the case of the most simple embodiment as a rapidly disintegrating administration form according to the invention, i.e. having a disintegration time of up to 15 min following application or following introduction into aqueous media, it emerged in the case of one test parson _ 7 that an apomorphine-containing film is superior to an apomorphine-containing tablet.
An improved contact of the pharmaceutical preparation with the oral mucosa can be achieved through selecting the auxiliary substances. It is known of certain orally applicable auXlllary agents which are frequently used in pharmaceutics that they have mucoadhesive properties.
Exam4ples for such mucoadhesive substances are polyacrylic acid,-carboxymethylcellulose, tragacanth, alginic acid, gelatin, hydroxymethylcellulose, methylcellulose and gum arabic. In addition, it is known of various non-mucoadhesive substances that in certain mixing ratios they also develop mucoadhesive properties. An example for such a mixture is glycerol monooleate/water in a ratio of 84:16 (Engstrom et al., Pharm. Tech. Eur. 7 [1995, No. 2, pages 14-17).
Tahere mucoadhesive auxiliary substances are used, it is preferable for the administration form of the pharma-ceutical preparation according to the invention to have a two-layer or multi-layer structure, whereby only that layer which upon application is to come into contact with the mucosa should be equipped with mucoadhesive properties.
This prevents the preparation from conglutinating various parts of the mucosa with each other, which would lead to sensations of considerable discomfort during application.
Good adhesion of the administration form leads to the active substance being optimally available for absorption.
In addition, it is the prerequisite for a further, preferred embodiment of the invention, namely a controlled-release preparation. In the preparation according to the invention, the active substance amount, respectively the portion of the active substance dose administered, that is absorbed is dependent not only on the contact surface and the permeability of the mucosa, but also on the duration of contact. =n order to allow a larger amount of active ingredient to enter the body via the relatively small surface of the oral mucosa, it may be necessary to permit a long duration of contact; this, however requires that the preparation does not disintegrate too rapidly, but, through the addition of auxiliary substances that are slightly or slowly soluble in saliva, releases the active substance for the desired duration of time. Suitable auxiliary substances may be, for exaiqple, film-forming polymers having poor water-solubility, such as ethylcellulose, cellulose acetate, highly hydrolized polyvinyl alcohol and many more.
Administration of apomorphine typically results in unwanted side effects. In the first place, nausea, vomiting and decrease in blood pressure are to be mentioned. These side affects must be regarded as being serious and as imposing limits on therapy. However, it is known that through simultaneous administration of antiemetically effective dopamine antagonists such as metoclopramide, but especially domperidone, the occurrence of side effects can be eliminated or alleviated without the amorphine losing its anti-Parkinson action.
A further preferred embodiment of the present invention therefore contains as active substances apomorphine in combination with a dopamine antagonist in a combination.
=n the following, preparation examples will be given of the pharmaceutical preparation according to the invention:
Example 1:

7 g 8s0 .

g TiOz .
18.4 g polyvinyl pyrrolidone 18.9,g potato starch 23.3 g ethanol 4.0 g~~H2O
16.6 g~~apomorphine HCI
1.8 g~~aroma 1.2 g~~sweetener 3.0 g~~acidifying agent H2O is placed in a heatable, mixing vessel which can be evacuated. Polyvinylpyrrolidone is dispersed therein and allowed to swell. TiO2 is dispersed in this mass. To accelerate the swelling process of the polivinyl-pyrrolidone, the mass be heated. At room temperature, potato starch is despersed in the homogeneous mass.
Ethanol, residual H2O and apomorphine HCI are added while stirring. The mass is heated to 100°C while stirring. After cooling to room temperature, aroma, sweetener and acidifying agent are added, and the mass is degasified under vacuum. The mass is spread onto a suitable carrier material using a doctor knife, and is dried for 30 minutes at 80°C. Dosage units are punched out with a wad punch.

Example 2:
135.8 g~~H2O
35.7 g~~polyvinyl alcohol 9.9 g~~TiO2 46.5 g~~SiO2 20.0 g~~glycerol (85%) 50.0 g~~apomorphine HCI
4.8 g~~aroma 3.2 g~~sweetener 8.0 g~~acidifying agent H2O is placed in a heatable mixing vessel which can be evacuated, and TiO2 is dispersed therein. Polyvinyl alcohol and apomorphine HCI are powdered thereto, and are homogenized while heating to about 80°C. The mass is degasified under vacuum. After cooling to room temperature, SiOs, glycerol, aroma, sweetener and acidifying agent are added and homogenized. The mass is degasified under vacuum.
The mass is spread onto a suitable carrier material using a doctor knife, and is dried for 30 minutes at 80~C. Dosage units are punched out with a wad punch.

Claims (9)

11
1. Pharmaceutical preparation exhibiting a rapid onset of action, for the treatment of off-phases of Parkinson's disease, having a content of apomorphine or one of its therapeutically acceptable salts, characterized by a foil-shaped, paper-shaped or wafer-shaped administration form for application in the oral cavity and release of active substance to the oral mucosa.
2. Pharmaceutical preparation according to claim 1, characterized in that it is equipped with mucoadhesive properties by the addition of an adhesion-promoting auxiliary substance or auxiliary substance mixture.
3. Pharmaceutical preparation according to claim 2, characterized is that it is multilayered, with only one layer having mucoadhesive properties.
4. Pharmaceutical preparation according to one or more of claims 1 - 3, characterized in that it contains at least one further active substance.
5. Pharmaceutical preparation according to claim 4, characterized in that it contains at least one active substance which suppresses or alleviates an unwanted side effect of apomorphine.
6. Pharmaceutical preparation according to claim 5, characterized by a content of domperidone.
7. Pharmaceutical preparation according to one or more of the preceding claims, characterized in that it is present separated into doses, and can be brought into direct contact with the oral mucosa.
8. Pharmaceutical preparation according to one or more of the preceding claims, characterized in that it is adapted to disintegrate quickly upon contact with liquid media.
9. Pharmaceutical preparation according to one or more of the preceding claims, characterized in that it contains agents for the retarded release of active substance.
CA002274893A 1996-12-16 1997-11-21 Active substance carrier for releasing apomorphine into the buccal cavity Abandoned CA2274893A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19652268A DE19652268C2 (en) 1996-12-16 1996-12-16 Medicinal preparation for the release of apomorphine in the oral cavity
DE19652268.4 1996-12-16
PCT/EP1997/006529 WO1998026763A1 (en) 1996-12-16 1997-11-21 Active substance carrier for releasing apomorphine into the buccal cavity

Publications (1)

Publication Number Publication Date
CA2274893A1 true CA2274893A1 (en) 1998-06-25

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ID=7814859

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CA002274893A Abandoned CA2274893A1 (en) 1996-12-16 1997-11-21 Active substance carrier for releasing apomorphine into the buccal cavity

Country Status (8)

Country Link
EP (1) EP0959875A1 (en)
JP (1) JP2001506612A (en)
KR (1) KR20000057627A (en)
AU (1) AU746373B2 (en)
CA (1) CA2274893A1 (en)
DE (1) DE19652268C2 (en)
NO (1) NO992944L (en)
WO (1) WO1998026763A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7910132B2 (en) 1998-09-24 2011-03-22 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
CN101005824B (en) * 2004-06-17 2012-05-30 高露洁-棕榄公司 Oral care film
US9044475B2 (en) 2009-06-12 2015-06-02 Cynapsus Therapeutics, Inc. Sublingual apomorphine
US9283219B2 (en) 2010-12-16 2016-03-15 Cynapsus Therapeutics, Inc. Sublingual films
US10449146B2 (en) 2015-04-21 2019-10-22 Sunovion Pharmaceuticals Inc. Methods of treating parkinson's disease by administration of apomorphine to an oral mucosa

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US6596298B2 (en) 1998-09-25 2003-07-22 Warner-Lambert Company Fast dissolving orally comsumable films
US6291471B1 (en) 1998-12-17 2001-09-18 Abb Holdings, Inc. Use of apomorphine for the treatment of organic erectile dysfunction in males
US6540978B1 (en) 1998-12-23 2003-04-01 Mount Sinai School Of Medicine Of New York University Inhibitors of the bitter taste response
US7314716B2 (en) 1999-11-19 2008-01-01 Mount Sinai School Of Medicine Gustducin γ subunit materials and methods
US7067116B1 (en) 2000-03-23 2006-06-27 Warner-Lambert Company Llc Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1
USRE44145E1 (en) 2000-07-07 2013-04-09 A.V. Topchiev Institute Of Petrochemical Synthesis Preparation of hydrophilic pressure sensitive adhesives having optimized adhesive properties
US20050215727A1 (en) 2001-05-01 2005-09-29 Corium Water-absorbent adhesive compositions and associated methods of manufacture and use
DE60233217D1 (en) 2001-05-01 2009-09-17 Corium Internat Inc HYDROGEL COMPOSITIONS
US8840918B2 (en) 2001-05-01 2014-09-23 A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences Hydrogel compositions for tooth whitening
US8206738B2 (en) 2001-05-01 2012-06-26 Corium International, Inc. Hydrogel compositions with an erodible backing member
US8541021B2 (en) 2001-05-01 2013-09-24 A.V. Topchiev Institute Of Petrochemical Synthesis Hydrogel compositions demonstrating phase separation on contact with aqueous media
DE10252726B4 (en) * 2002-11-13 2008-05-08 Lts Lohmann Therapie-Systeme Ag Multilayer transmucosal therapeutic system
EP1583431A1 (en) * 2002-11-14 2005-10-12 Givaudan SA Edible film containing food acid
KR100945741B1 (en) * 2003-01-16 2010-03-05 부광약품 주식회사 Oral spray preparation of apomorphine hydrochloride
CA2554649C (en) 2004-01-30 2015-10-27 Corium International, Inc. Rapidly dissolving film for delivery of an active agent
CA2751884C (en) 2009-01-14 2018-09-25 Corium International, Inc. Transdermal administration of tamsulosin
US10806703B2 (en) * 2012-01-20 2020-10-20 Lts Lohmann Therapie-System Ag Transmucosal administration system for a pharmaceutical drug
WO2015070156A1 (en) * 2013-11-11 2015-05-14 Impax Laboratories, Inc. Rapidly disintegrating formulations and methods of use

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US3972995A (en) * 1975-04-14 1976-08-03 American Home Products Corporation Dosage form
DE2746414A1 (en) * 1977-10-15 1979-04-26 Gerlach Eduard Chem Fab Foil-like tape for dispensing measured amts. of substance - consisting of the substance, binding agent and adjuvants, tape length being proportional to weight of substance
DK0758895T3 (en) * 1994-04-22 2000-06-13 Pentech Pharmaceuticals Inc Sublingual dosage forms containing apomorphine for use in the treatment of erectile dysfunction
FR2732896B1 (en) * 1995-04-11 1997-06-13 Prographarm Lab TRANSDERMAL PHARMACEUTICAL FORM FOR PERCUTANEOUS ADMINISTRATION OF APOMORPHINE

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7910132B2 (en) 1998-09-24 2011-03-22 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
US8454996B2 (en) 1998-09-24 2013-06-04 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
US8512747B2 (en) 1998-09-24 2013-08-20 Orexo Ab Pharmaceutical composition for the treatment of acute disorders
CN101005824B (en) * 2004-06-17 2012-05-30 高露洁-棕榄公司 Oral care film
US9669020B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9669019B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9326981B2 (en) 2009-06-12 2016-05-03 Cynapsus Therapeutics, Inc. Sublingual apomorphine
US10420763B2 (en) 2009-06-12 2019-09-24 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9044475B2 (en) 2009-06-12 2015-06-02 Cynapsus Therapeutics, Inc. Sublingual apomorphine
US9669021B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9669018B2 (en) 2009-06-12 2017-06-06 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
EP2952191B1 (en) 2009-06-12 2018-08-22 Sunovion Pharmaceuticals Inc. Sublingual apomorphine
US9283219B2 (en) 2010-12-16 2016-03-15 Cynapsus Therapeutics, Inc. Sublingual films
US10285953B2 (en) 2010-12-16 2019-05-14 Sunovion Pharmaceuticals Inc. Sublingual films
US9427412B2 (en) 2010-12-16 2016-08-30 Cynapsus Therapeutics, Inc. Sublingual films
US11419769B2 (en) 2010-12-16 2022-08-23 Sunovion Pharmaceuticals Inc. Sublingual films
US10449146B2 (en) 2015-04-21 2019-10-22 Sunovion Pharmaceuticals Inc. Methods of treating parkinson's disease by administration of apomorphine to an oral mucosa
US10959943B2 (en) 2015-04-21 2021-03-30 Sunovion Pharmaceuticals Inc. Methods of treating Parkinson's disease by administration of apomorphine to an oral mucosa

Also Published As

Publication number Publication date
JP2001506612A (en) 2001-05-22
AU5654798A (en) 1998-07-15
NO992944D0 (en) 1999-06-16
AU746373B2 (en) 2002-04-18
DE19652268C2 (en) 2000-06-29
KR20000057627A (en) 2000-09-25
EP0959875A1 (en) 1999-12-01
DE19652268A1 (en) 1998-06-18
WO1998026763A1 (en) 1998-06-25
NO992944L (en) 1999-06-16

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