EP1558209A1 - Transmucosale pharmazeutische darreichungsform - Google Patents

Transmucosale pharmazeutische darreichungsform

Info

Publication number
EP1558209A1
EP1558209A1 EP03758008A EP03758008A EP1558209A1 EP 1558209 A1 EP1558209 A1 EP 1558209A1 EP 03758008 A EP03758008 A EP 03758008A EP 03758008 A EP03758008 A EP 03758008A EP 1558209 A1 EP1558209 A1 EP 1558209A1
Authority
EP
European Patent Office
Prior art keywords
dosage form
active ingredient
form according
derivative
compound
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.)
Ceased
Application number
EP03758008A
Other languages
German (de)
English (en)
French (fr)
Inventor
Hans-Rainer Hoffmann
Reinhard Kleinsorgen Von
Werner Wessling
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
LTS Lohmann Therapie Systeme AG
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 LTS Lohmann Therapie Systeme AG filed Critical LTS Lohmann Therapie Systeme AG
Publication of EP1558209A1 publication Critical patent/EP1558209A1/de
Ceased legal-status Critical Current

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
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K9/7007—Drug-containing films, membranes or sheets
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence

Definitions

  • the invention relates to administration forms, preferably sheet-like, liquid-crystalline structures or phases which form liquid in an aqueous environment, in particular oral administration forms, by means of which controlled absorption of active substances in the oral cavity, in particular in the non-keratinized areas, is made possible, and which comprises a matrix on the Have the basis of phospholipids as basic substances.
  • the invention relates to dosage forms of the type mentioned, which are designed in the form of wafers.
  • the invention includes a method for producing such dosage forms.
  • the invention enables the controlled delivery of a wide range of active ingredients to the oral mucosa, e.g. B. the delivery of active ingredients that are effective in the CNS (central nervous system), in the cardiovascular system, in the muscular and skeletal system and in the respiratory system of the human body, as well as those that are effective as anti-infectives, antibiotics and hormones.
  • Preferred active substances for the dosage form according to the invention are those which are suitable for the treatment of drug abuse or drug dependence, in particular for the treatment of nicotine and alcohol dependence of different origins.
  • the substances or classes of substances listed below are particularly suitable for this indication: 7-azabicyclo (2.2.1) -heptane and -heptene and their derivatives; Ebibatidine and derivatives; condensed indole derivatives; Benzylidene and cinnamylidene annabasienes; Mecamylamine, hypericin, the cannabinoid receptor (CBI) antagonist SR 141716, befloxatone, oxazolidinone derivatives such as e.g. B.
  • CBI cannabinoid receptor
  • compositions e.g. B.
  • Buccal and sublingual tablets that release active ingredients in the oral cavity, which are then absorbed through the oral mucosa, are advantageous in many ways. They facilitate the oral administration of medication to certain patients who find it difficult to take other oral dosage forms, for example due to difficulty swallowing. Since absorption occurs through the oral mucosa and bypasses the gastrointestinal passage, rapid onset of action and a high level of active ingredient utilization are guaranteed.
  • sheet-like, wafer-like dosage forms also called “wafers” come into consideration as oral dosage forms, which have the properties mentioned above. These are notable for the rapid release of medication due to their small layer thickness and rapid disintegration or dissolvability and other active ingredients in the oral cavity.
  • such wafer-like pharmaceutical forms are composed of film-forming, water-soluble polymers, for example certain cellulose derivatives.
  • the matrix structure of the “wafer” or this structure dissolves and the active substances in it are released.
  • the onset and the time course of the release of active substance depend to a large extent on the thickness of the pharmaceutical form (the "wafer") and on the type of matrix structure.
  • the structure of the matrix determines the release (profile); the type of polymer or
  • the type and composition of the polymer mixture determines the adhesion to the mucous membrane. Consequently, the thickness of such dosage forms is essentially determined by the type and amount of the active ingredient which they are intended to contain and release.
  • the dwell time of these dosage forms at the application site (e.g. mouth) or the disintegration time is preferably in the range from 5 sec to 1 min, more preferably in the range from 10 sec to 1 min, and most preferably in the range from 10 sec up to 30 sec.
  • the matrix of these dosage forms contains a water-soluble polymer or mixtures of such polymers as basic substances. Synthetic or semi-synthetic polymers or biopolymers of natural origin are preferably used, which are film-forming and water-soluble and / or which, for. B. are also suitable for foam formation.
  • Polymers which are preferably selected from the group comprising cellulose derivatives, polyvinyl alcohol, polyacrylates and polyvinyl pyrrolidone, are described here as particularly suitable carriers (matrix).
  • cellulose derivatives hydroxypropyl methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose and methyl cellulose are particularly preferred, as are other substituted cellulose derivatives.
  • water-soluble polysaccharides that are of plant, microbial or synthetic origin, in particular those polysaccharides that are not cellulose derivatives, such as. B. pullulan, xanthan, alginates, dextrans, agar-agar, pectins and carrageenan.
  • Proteins preferably gelatin or other gel-forming proteins and protein hydrolyzates are also named.
  • the carrier materials suitable in the above-mentioned patents or published documents also include caseinates, whey and vegetable proteins, gelatin and (chicken) protein and mixtures thereof.
  • a carrier material for the administration of active substances is known which has such a composition that it dissolves quickly after oral ingestion upon contact with saliva. It is a porous dehydrated Velcro-like carrier, in particular based on proteins, polysaccharides and / or phorspholipids, such as. B. lecithin, but a specification of said lecithin is not specified.
  • the gelatin-polysaccharide carriers described can also be used in the form of wafers. The carrier substances are rehydrated at the latest when they come into contact with saliva, giving them a sticky surface which causes the dosage form to adhere to the mouth.
  • the base body of the transmucosal dosage form consists of a solid solution of the active ingredient a) in a phosphatidylcholine, the fatty acid residues of which are at least 90% saturated, or b) in a mixture of the phosphatidylcholine mentioned under a) with a
  • Copolymer of maleic acid with an alkyl vinyl ether is a copolymer of maleic acid with an alkyl vinyl ether.
  • the base body according to a) and b) can additionally other pharmaceutically acceptable auxiliaries and additives, for. B. contain a polyvinylpyrrolidone medium chain length, which also serves to improve the taste of the dosage form according to the invention.
  • the phosphatidylcholine fractions Epikuron 180 and Epikuron 180H have proven to be particularly suitable for the dosage form according to the invention.
  • these phosphatidylcholines When dissolved in pure alcohol, these phosphatidylcholines can be used to produce solid transparent films in which the active ingredient is present as a solid solution. These films adhere to the oral mucosa for a sufficiently long time. When water enters these films, myelin-like structures emerge from the film surface, in which the active ingredient is still dissolved. These are not vesicular active substance “encapsulated” microscopic units, but rather lamellar mesophases, in the lamellar regions of which the active substance is molecular. These lamellar mesophases are particularly suitable for attaching to the mucosa. Depending on the content of residual solvent (ethanol) or the addition of small amounts of pure hydrocarbons (e.g. paraffin of low viscosity) or triglycerides with a low hydroxyl number, this myelin formation can be controlled up to a spontaneously emulsifying gel system similar to a drilling oil emulsion.
  • ethanol

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Addiction (AREA)
  • Psychiatry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (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)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP03758008A 2002-11-08 2003-10-17 Transmucosale pharmazeutische darreichungsform Ceased EP1558209A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10251963A DE10251963A1 (de) 2002-11-08 2002-11-08 Transmucosale pharmazeutische Darreichungsform
DE10251963 2002-11-08
PCT/EP2003/011529 WO2004041239A1 (de) 2002-11-08 2003-10-17 Transmucosale pharmazeutische darreichungsform

Publications (1)

Publication Number Publication Date
EP1558209A1 true EP1558209A1 (de) 2005-08-03

Family

ID=32115381

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03758008A Ceased EP1558209A1 (de) 2002-11-08 2003-10-17 Transmucosale pharmazeutische darreichungsform

Country Status (14)

Country Link
US (1) US20060013864A1 (pl)
EP (1) EP1558209A1 (pl)
JP (1) JP2006506406A (pl)
KR (1) KR20050084938A (pl)
CN (1) CN1694685A (pl)
AU (1) AU2003274030B2 (pl)
BR (1) BR0315911A (pl)
CA (1) CA2497848A1 (pl)
DE (1) DE10251963A1 (pl)
MX (1) MXPA05004892A (pl)
PL (1) PL375142A1 (pl)
RU (1) RU2342925C2 (pl)
WO (1) WO2004041239A1 (pl)
ZA (1) ZA200502443B (pl)

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3706831A (en) * 1971-05-14 1972-12-19 Abbott Lab Method for treatment of drug addiction
SE8206744D0 (sv) * 1982-11-26 1982-11-26 Fluidcarbon International Ab Preparat for kontrollerad avgivning av substanser
JPS6115829A (ja) * 1984-06-29 1986-01-23 Toyobo Co Ltd 口腔粘膜適用徐放性ニフエジピン製剤
DE3910543A1 (de) * 1989-04-01 1990-10-11 Lohmann Therapie Syst Lts Transdermales therapeutisches system mit erhoehtem wirkstofffluss und verfahren zu seiner herstellung
US5079018A (en) * 1989-08-14 1992-01-07 Neophore Technologies, Inc. Freeze dry composition and method for oral administration of drugs, biologicals, nutrients and foodstuffs
US5998409A (en) * 1992-03-12 1999-12-07 Smithkline Beecham Plc Condensed indole derivatives as 5HT4 -receptor antagonists
US5977144A (en) * 1992-08-31 1999-11-02 University Of Florida Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines
US5817679A (en) 1993-04-01 1998-10-06 University Of Virginia 7-Azabicyclo 2.2.1!-heptane and -heptene derivatives as cholinergic receptor ligands
US5453523A (en) * 1993-06-16 1995-09-26 Emulsion Technology, Inc. Process for obtaining highly purified phosphatidylcholine
WO1995007078A1 (en) 1993-09-10 1995-03-16 Cytomed, Inc. Epibatidine and derivatives thereof as cholinergic receptor agonists and antagonists
US6117889A (en) * 1994-04-01 2000-09-12 University Of Virginia 7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents
JPH07291854A (ja) * 1994-04-26 1995-11-07 Tanabe Seiyaku Co Ltd 溶解性の改善された医薬品製剤
AU2703795A (en) * 1994-06-23 1996-01-19 Procter & Gamble Company, The Treatment of nicotine craving and/or smoking withdrawal symptoms with a transdermal or transmucosal composition containing nicotine and caffeine or xanthine
DE19701949A1 (de) * 1997-01-13 1998-07-16 Jenapharm Gmbh Transdermales therapeutisches System
CN1155410C (zh) * 1997-10-03 2004-06-30 卡里药品公司 治疗尼古丁成瘾的含有尼古丁受体拮抗剂和抗抑郁药或抗焦虑药的组合物
US20040028735A1 (en) * 1997-11-14 2004-02-12 Unchalee Kositprapa Pharmaceutical formulation
SE9803986D0 (sv) * 1998-11-23 1998-11-23 Pharmacia & Upjohn Ab New compositions
US6248363B1 (en) * 1999-11-23 2001-06-19 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
AR025609A1 (es) * 1999-09-13 2002-12-04 Hoffmann La Roche Formulaciones lipidas solidas
US6264981B1 (en) * 1999-10-27 2001-07-24 Anesta Corporation Oral transmucosal drug dosage using solid solution
DE10024413A1 (de) * 2000-05-19 2001-12-06 Mika Pharma Gmbh Pharmazeutische und/oder kosmetische Zubereitung
DE10032456A1 (de) * 2000-07-04 2002-01-31 Lohmann Therapie Syst Lts Schnell zerfallende Darreichungsform zur Freisetzung von Wirkstoffen im Mundraum oder in Körperhöhlen
DE10107659B4 (de) * 2001-02-19 2008-03-13 Lts Lohmann Therapie-Systeme Ag Mucoadhäsive zerfallsfähige Arzneizubereitung zur Wirkstoffverabreichung in der Veterinär- und Humanmedizin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2004041239A1 *

Also Published As

Publication number Publication date
CA2497848A1 (en) 2004-05-21
AU2003274030A1 (en) 2004-06-07
ZA200502443B (en) 2005-09-26
MXPA05004892A (es) 2005-07-22
RU2005113169A (ru) 2006-01-20
US20060013864A1 (en) 2006-01-19
AU2003274030B2 (en) 2008-09-04
PL375142A1 (pl) 2005-11-28
CN1694685A (zh) 2005-11-09
KR20050084938A (ko) 2005-08-29
RU2342925C2 (ru) 2009-01-10
BR0315911A (pt) 2005-09-13
WO2004041239A1 (de) 2004-05-21
DE10251963A1 (de) 2004-05-19
JP2006506406A (ja) 2006-02-23

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