EP1558209A1 - Transmucosale pharmazeutische darreichungsform - Google Patents
Transmucosale pharmazeutische darreichungsformInfo
- 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
Links
- 239000004480 active ingredient Substances 0.000 claims abstract description 26
- 239000000203 mixture Substances 0.000 claims abstract description 7
- -1 alkyl vinyl ether Chemical compound 0.000 claims abstract description 6
- 239000006104 solid solution Substances 0.000 claims abstract description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229920001577 copolymer Polymers 0.000 claims abstract description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims abstract description 3
- 239000011976 maleic acid Substances 0.000 claims abstract description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000002552 dosage form Substances 0.000 claims description 24
- 210000000214 mouth Anatomy 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- 239000013543 active substance Substances 0.000 claims description 9
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 6
- 102000018208 Cannabinoid Receptor Human genes 0.000 claims description 3
- 108050007331 Cannabinoid receptor Proteins 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 2
- SNZSSCZJMVIOCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1N2 SNZSSCZJMVIOCR-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- IALVDLPLCLFBCF-CHWSQXEVSA-N befloxatone Chemical compound O=C1O[C@@H](COC)CN1C1=CC=C(OCC[C@@H](O)C(F)(F)F)C=C1 IALVDLPLCLFBCF-CHWSQXEVSA-N 0.000 claims description 2
- 229950000017 befloxatone Drugs 0.000 claims description 2
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000005313 fatty acid group Chemical group 0.000 claims description 2
- BTXNYTINYBABQR-UHFFFAOYSA-N hypericin Chemical compound C12=C(O)C=C(O)C(C(C=3C(O)=CC(C)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 BTXNYTINYBABQR-UHFFFAOYSA-N 0.000 claims description 2
- 229940005608 hypericin Drugs 0.000 claims description 2
- PHOKTTKFQUYZPI-UHFFFAOYSA-N hypericin Natural products Cc1cc(O)c2c3C(=O)C(=Cc4c(O)c5c(O)cc(O)c6c7C(=O)C(=Cc8c(C)c1c2c(c78)c(c34)c56)O)O PHOKTTKFQUYZPI-UHFFFAOYSA-N 0.000 claims description 2
- 150000002475 indoles Chemical class 0.000 claims description 2
- IMYZQPCYWPFTAG-IQJOONFLSA-N mecamylamine Chemical compound C1C[C@@H]2C(C)(C)[C@@](NC)(C)[C@H]1C2 IMYZQPCYWPFTAG-IQJOONFLSA-N 0.000 claims description 2
- 229960002525 mecamylamine Drugs 0.000 claims description 2
- SSKVDVBQSWQEGJ-UHFFFAOYSA-N pseudohypericin Natural products C12=C(O)C=C(O)C(C(C=3C(O)=CC(O)=C4C=33)=O)=C2C3=C2C3=C4C(C)=CC(O)=C3C(=O)C3=C(O)C=C(O)C1=C32 SSKVDVBQSWQEGJ-UHFFFAOYSA-N 0.000 claims description 2
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 201000009032 substance abuse Diseases 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 4
- XOLAHDCBBMDPCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]hept-3-ene Chemical compound C1C(N2)CCC2=C1 XOLAHDCBBMDPCR-UHFFFAOYSA-N 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 125000001095 phosphatidyl group Chemical group 0.000 abstract 2
- 235000012431 wafers Nutrition 0.000 description 10
- 239000011159 matrix material Substances 0.000 description 7
- 210000002200 mouth mucosa Anatomy 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 210000003296 saliva Anatomy 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006189 buccal tablet Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 239000006190 sub-lingual tablet Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920003169 water-soluble polymer Polymers 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- AJWFNQNFPHYNIK-UHFFFAOYSA-N 3-azabicyclo[2.2.1]hept-3-ene Chemical compound C1C(C2)CCC2=N1 AJWFNQNFPHYNIK-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010049244 Ankyloglossia congenital Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108010082495 Dietary Plant Proteins Proteins 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 206010057852 Nicotine dependence Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241001634922 Tausonia pullulans Species 0.000 description 1
- 208000025569 Tobacco Use disease Diseases 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 210000003254 palate Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
- 229960000761 pemoline Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
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)
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)
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 |
-
2002
- 2002-11-08 DE DE10251963A patent/DE10251963A1/de not_active Withdrawn
-
2003
- 2003-10-17 KR KR1020057007931A patent/KR20050084938A/ko not_active Application Discontinuation
- 2003-10-17 BR BR0315911-6A patent/BR0315911A/pt not_active IP Right Cessation
- 2003-10-17 CA CA002497848A patent/CA2497848A1/en not_active Abandoned
- 2003-10-17 JP JP2004548754A patent/JP2006506406A/ja active Pending
- 2003-10-17 US US10/533,926 patent/US20060013864A1/en not_active Abandoned
- 2003-10-17 AU AU2003274030A patent/AU2003274030B2/en not_active Ceased
- 2003-10-17 EP EP03758008A patent/EP1558209A1/de not_active Ceased
- 2003-10-17 RU RU2005113169/15A patent/RU2342925C2/ru not_active IP Right Cessation
- 2003-10-17 MX MXPA05004892A patent/MXPA05004892A/es active IP Right Grant
- 2003-10-17 PL PL03375142A patent/PL375142A1/pl not_active Application Discontinuation
- 2003-10-17 WO PCT/EP2003/011529 patent/WO2004041239A1/de active Application Filing
- 2003-10-17 CN CNA2003801007385A patent/CN1694685A/zh active Pending
-
2005
- 2005-03-24 ZA ZA200502443A patent/ZA200502443B/en unknown
Non-Patent Citations (1)
Title |
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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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