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WO2000067723A2 - Form of administration for applying in body orifices - Google Patents

Form of administration for applying in body orifices Download PDF

Info

Publication number
WO2000067723A2
WO2000067723A2 PCT/DE2000/001512 DE0001512W WO0067723A2 WO 2000067723 A2 WO2000067723 A2 WO 2000067723A2 DE 0001512 W DE0001512 W DE 0001512W WO 0067723 A2 WO0067723 A2 WO 0067723A2
Authority
WO
WIPO (PCT)
Prior art keywords
capsule
capsule according
active ingredient
rapidly disintegrating
namely
Prior art date
Application number
PCT/DE2000/001512
Other languages
German (de)
French (fr)
Other versions
WO2000067723A3 (en
Inventor
Roland Bodmeier
Original Assignee
Roland Bodmeier
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 Roland Bodmeier filed Critical Roland Bodmeier
Priority to EP00943585A priority Critical patent/EP1178777A2/en
Priority to AU58028/00A priority patent/AU5802800A/en
Priority to DE10081194T priority patent/DE10081194D2/en
Publication of WO2000067723A2 publication Critical patent/WO2000067723A2/en
Publication of WO2000067723A3 publication Critical patent/WO2000067723A3/en

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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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • 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
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin

Definitions

  • the present invention relates to capsules for the application of active substances which rapidly enter body openings, e.g. disintegrate in the oral cavity or after rectal or vaginal application.
  • Solid dosage forms e.g. tablets or capsules
  • enter the stomach and release the drug which is then absorbed in the gastrointestinal tract or acts locally.
  • swallowing solid dosage forms is difficult and can lead to compliance problems (e.g. not taking or spitting out the dosage form). Swallowing solid dosage forms without liquid is difficult or impossible.
  • traveling taking solid dosage forms with water is often not recommended for hygienic reasons.
  • the application of solid single-body systems is also difficult in animals.
  • the rapidly disintegrating dosage forms described also have some disadvantages, such as lack of mechanical stability and high sensitivity to moisture.
  • the tablets produced by lyophilization are very fragile, for example they cannot be pressed out of a blister pack, but have to be removed. Also, the tablet-like dosage forms are usually made with very low hardness in order to accelerate their disintegration To enable increased porosity or to reduce the damage to coated active ingredient particles.
  • the object of this invention was therefore to develop a rapidly disintegrating dosage form which avoids many of the problems mentioned above.
  • a capsule for applying active substances comprising at least one macromolecule which is soluble and / or rapidly disintegrating in aqueous liquids, or a mixture of at least two of these substances, the capsule rapidly disintegrating into body openings after application .
  • the object is achieved according to the invention in that a capsule for oral administration of active ingredients is made available, the capsule rapidly disintegrating in the mouth or in the oral cavity.
  • the object is achieved in that a capsule for vaginal, rectal or nasal Application of active ingredients is provided, the capsule rapidly disintegrating after insertion into the body opening.
  • the object is achieved in that a capsule quickly disintegrates after being introduced into body openings which have arisen as a result of surgical interventions or injuries.
  • the macromolecule is selected from natural and / or synthetic polymers, such as proteins and peptides, for example gelatin, albumin, polysaccharides, for example agar-agar, alginates, carageen, chitosan, dextrin, dextran, pectin, starch and their derivatives, gums, cellulose derivatives , for example hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, polyacrylates, namely polyacrylic acid, polyacrylamide, polyethylene glycol, polyvinyl alcohol (also partially hydrolyzed), polyvinyl pyrrolidone, polyoxyethylene oxypropylene and
  • natural and / or synthetic polymers such as proteins and peptides, for example gelatin, albumin, polysaccharides, for example agar-agar, alginates, carageen, chitosan, dextrin, dextran, pectin, starch and their derivatives, gums,
  • a capsule is preferred according to the invention, one or more disintegrants, swelling agents (swelling agents) and / or solubilizers or mixtures thereof being contained as further auxiliaries.
  • the disintegration accelerator is selected from, for example, effervescent salts, sugar, sucrose, sorbitol, mannitol, sucrose. It is also preferred according to the invention that further auxiliaries, namely flavorings, sweeteners, colorants, preservatives, gelling agents, fillers, pigments, wetting agents (surfactants) and plasticizers are contained.
  • the capsule according to the invention is further characterized in that the capsule shell has micropores.
  • the capsule shell encloses cavities in the form of gas bubbles.
  • the capsule according to the invention itself comprises an active ingredient in the capsule shell.
  • the active substance-containing filling is solid, semi-solid or liquid.
  • the active substance is in retarded form.
  • the active ingredient is present in taste-masked form.
  • Another object of the present invention is a medicament comprising a capsule according to the invention and a pharmaceutical preparation contained therein, comprising at least one active pharmaceutical ingredient and, if appropriate, further pharmaceutically acceptable auxiliaries and additives.
  • the object of the invention was therefore achieved with a rapidly disintegrating capsule-like dosage form.
  • the active ingredient / excipient mixture is filled into a rapidly disintegrating capsule shell.
  • the capsule disintegrates quickly or quickly dissolves in the oral cavity, the solid or liquid contents are then swallowed.
  • Rapidly disintegrating is a broad term and means that the capsule shell quickly loses its shape after application in the oral cavity and can be swallowed quickly with the contents.
  • the disintegration can be positively influenced by moving the capsule (eg by moving the tongue).
  • the disintegration time is a few minutes, but preferably less than 30 seconds.
  • the capsule according to the invention has a number of advantages.
  • the coated active ingredient particles are e.g. not exposed to high pressures.
  • the capsule material used according to the invention can be any material which is soluble or disintegrating in aqueous liquids.
  • Macromolecules which dissolve or disintegrate rapidly in water are preferably used. These include both natural and synthetic polymers, such as proteins / peptides (e.g. gelatin, albumin), polysaccharides (e.g. agar-agar, alginates, carageen, chitosan, dextrin, dextran, pectin, starch and their derivatives, gums of natural origin) cellulose derivatives (e.g. hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose), polyacrylates (e.g. polyacrylic acid, polyacrylamide), polyethylene glycol, polyvinyl alcohol (also partially hydrolyzed),
  • proteins / peptides e.g. gelatin, albumin
  • polysaccharides e.g. agar-agar, alginates, carageen, chi
  • Molecular weight plays an important role in the case of polymers; capsule materials with a low molecular weight disintegrate or usually dissolve more quickly. Higher concentration liquid systems can also be produced with the low molecular weight oligomers / polymers.
  • the molecular weight of the polymers can be determined, for example, by hydrolytic or enzymatic degradation can be reduced. In the case of some polymers (eg gelatin) the molecular weight can be reduced, for example, by heating (eg autoclaving).
  • the capsule materials can also be used in combination.
  • Rapidly disintegrating / rapidly dissolving auxiliaries e.g. disintegrants such as effervescent salt or sugar and sugar derivatives such as sorbitol, mannitol, mannitol, sorbitol, sucrose
  • disintegrants such as effervescent salt or sugar and sugar derivatives such as sorbitol, mannitol, mannitol, sorbitol, sucrose
  • Decay can also be affected by the porosity of the capsule shell.
  • Gas bubbles can be incorporated into the capsule shell to increase the porosity and thus to accelerate the disintegration during the capsule shell production (e.g. dispersion of gas in the liquid during the immersion process).
  • volatile components can be incorporated into the capsule shell during manufacture, which, when removed, result in a porous capsule shell.
  • auxiliary substances can also be incorporated into the capsule shell.
  • these include, for example, flavorings, sweeteners, colorants, preservatives, gelling agents (to support the formation of the capsule shell, for example during the immersion process), fillers, pigments, wetting agents (surfactants) and plasticizers.
  • the capsules can also be coated with a thin layer which, for example, reduces sensitivity to moisture or has a positive effect on the flow of saliva.
  • the active ingredient also in "treated form", for example micro / nanoparticles
  • the contents of the capsule contain the active ingredient and, if necessary, various auxiliary substances.
  • the contents can be solid, semi-solid or liquid.
  • the dosage forms according to the invention are normally used for active substances which are absorbed in the gastrointestinal tract or which act locally. However, absorption or local effects in the oral cavity is also possible.
  • the capsule can also be used in other body openings. This includes in particular the vaginal, rectal, nasal route of application and also body openings caused by surgical interventions or injuries.
  • the dosage forms according to the invention can be used for the administration of a large number of active substances or combinations of active substances. Possible drugs are listed in the textbook of pharmacology and toxicology "drug effects" by E. Mutschier,ticianliche Verlagsgesellschaftsch mbH.
  • the active ingredient may be in a delayed form.
  • the active ingredient can, for example, be incorporated into pellets (matrix or reservoir pellets), microparticles (eg microsphere or microcapsules) or colloidal particles (eg nanoparticles, liposomes).
  • Different retarding materials can be used, e.g. polymers with pH-dependent solubility (e.g. enteric polymers) or polymers insoluble in gastrointestinal juice (e.g. cellulose derivatives, acrylate derivatives, polyester) or biodegradable polymers (e.g. poly (lactide-co-glycolide) or lipids .
  • the active ingredient dissolution can be improved by known galenic methods (e.g. dissolving in a suitable solvent, embedding in carrier materials, reducing the particle size by physical or chemical methods - also nanoparticles, nanocrystals, encapsulation in colloidal carrier particles, such as liposomes, lipid or polymer nanoparticles ) and the active ingredient is added or incorporated into the product in this form.
  • galenic methods e.g. dissolving in a suitable solvent, embedding in carrier materials, reducing the particle size by physical or chemical methods - also nanoparticles, nanocrystals, encapsulation in colloidal carrier particles, such as liposomes, lipid or polymer nanoparticles
  • Oral hygiene used for oral use or ingestion become .
  • the contents can be solid, semi-solid or liquid.
  • the active ingredient or the active ingredient processed as described above can be dissolved and / or dispersed in a liquid and then filled into the capsule in liquid form.
  • the solid filling material can be in powder or granule form or also in the form of small tablets or pellets or rapidly disintegrating matrix systems.
  • the contents can also contain auxiliary substances. These include e.g. Flavors, flavors, sweeteners, disintegrants, wetting agents, colorants, flow regulators, fillers, binders.
  • An effervescent set can also be used to help the capsule contents disintegrate more quickly or to improve taste and stimulate salivation.
  • Auxiliaries known to the person skilled in the art can also be added, which improve the mouthfeel of the dosage form.
  • the invention also relates to processes for producing the dosage form according to the invention.
  • the capsule shells can be produced by known capsule production methods, analogous to the production of soft or hard capsules. This includes, for example, the immersion process, in which capsule-shaped metal pins are immersed in a liquid which contains the capsule materials / auxiliary substances, the liquid adheres to the surface of the pin and the capsule shells are obtained after drying.
  • the capsule materials and other auxiliary substances are described in a solvent or solvent mixture (preferably containing water) dissolved or dispersed.
  • the capsule shells can also be produced by immersing the pins in the melt and then cooling them.
  • the size and shape of the capsule shell is determined by the size and shape of the pins.
  • the capsules are manufactured by means of injection molding, in which the capsule mass is introduced into preformed forms.
  • the capsules can be filled with the contents and sealed by the process known to the person skilled in the art.
  • Capsule-shaped dip sticks (capsule size 00) were placed in a heated, autoclaved gelatin solution (20-40%) in the
  • Glycerol and sorbitol was dissolved, immersed and pulled out again. After drying, the capsule halves were pulled off, cut and put together. The capsule shells disintegrated in the oral cavity in less than 30 seconds.
  • Capsule-shaped dip sticks (capsule size 00) were immersed in an autoclaved gelatin solution (20-40%) in which glycerol and sorbitol were dissolved and fine air bubbles were dispersed, and pulled out again. After drying, the capsule halves were peeled off, cut, and put together. The capsule shells disintegrated in the oral cavity in less than 30 seconds.
  • the capsules produced according to Example 1 or 2 were filled with a mixture of lactose and microencapsulated paracetamol (taste masked, coated with ethyl cellulose) before the capsule shells were put together.
  • the capsules disintegrated in the oral cavity in less than 30 seconds.
  • the capsules produced according to Example 1 or 2 were filled with a mixture of microcrystalline cellulose, effervescent salt and propranolol HCl sustained release pellets (coated with ethyl cellulose) before the capsule shells were put together.
  • the capsules disintegrated in the oral cavity in less than 30 seconds.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to a capsule for applying active substances, comprising at least one macromolecule which is soluble in aqueous liquids and/or decomposes rapidly, or a mixture of at least two such substances.

Description

Beschreibung description
Darreichungsform zur Applikation in KörperöffnungenDosage form for application in body openings
Die vorliegende Erfindung betrifft Kapseln zur Applikation von Wirkstoffen, die rasch in Körperöffnungen, z.B. in der Mundhöhle oder nach rektaler oder vaginaler Applikation zerfallen.The present invention relates to capsules for the application of active substances which rapidly enter body openings, e.g. disintegrate in the oral cavity or after rectal or vaginal application.
Die meisten Arzneistoffe werden oral in entweder fester oder flüssiger Darreichungsform verabreicht . Feste Darreichungsformen (z.B. Tabletten oder Kapseln) werden geschluckt, gelangen in den Magen und setzen den Arzneistoff frei, der dann im Magen-Darm-Trakt resorbiert wird oder lokal wirkt. Für einige Patienten, z.B. Kinder oder ältere Patienten, ist das Schlucken fester Arzneiformen jedoch schwierig und kann zu Compliance- Problemen (z.B. Nichteinnahme oder Ausspucken der Arzneiform) führen. Auch das Schlucken fester Arzneiformen ohne Flüssigkeit ist schwierig oder unmöglich. Bei Reisen ist die Einnahme fester Darreichungsformen mit Wasser aus hygienischen Gründen häufig nicht empfehlenswert. Auch bei Tieren ist die Applikation fester Einkörpersysteme schwierig.Most drugs are administered orally in either solid or liquid form. Solid dosage forms (e.g. tablets or capsules) are swallowed, enter the stomach and release the drug, which is then absorbed in the gastrointestinal tract or acts locally. For some patients, e.g. Children or elderly patients, however, swallowing solid dosage forms is difficult and can lead to compliance problems (e.g. not taking or spitting out the dosage form). Swallowing solid dosage forms without liquid is difficult or impossible. When traveling, taking solid dosage forms with water is often not recommended for hygienic reasons. The application of solid single-body systems is also difficult in animals.
Es wurden daher verschiedene feste Darreichungsformen entwickelt, die sich rasch in der Mundhöhle (Mundspeichel) auflösen und dann ohne Flüssigkeit geschluckt werden können. DE 27 44 493 C2 beschreibt eine durch Lyophilisation hergestellte Darreichungsform inn Tablettenform mit einer porösen Matrix, die sich im Mundspeichel innerhalb weniger Sekunden auflöst. Dazu wird eine Wirkstoffhaltige autoklavierte Gelatinelösung in vorgeformte Vertiefungen (z.B. einer Blisterpackung) gegeben, eingefroren und durch Lyophilisation in eine poröse Matrix (Tablette) getrocknet. DE 40 18 247 C2 beschreibt schnell zerfallende folienförmige Darreichungsformen. US-A 5,762,961 und WO 93/13758 beschreiben Tabletten, die aufgrund ihrer hohen Porosität rasch zerfallen. Die Porosität wird dabei durch das Entfernen flüchtiger Hilfsstoffe nach der Tablettierung erreicht. US-A 5,464,632 und US-A 5,178,878 beschreiben schnell zerfallende Tabletten, die umhüllte Wirkstoffteilchen enthalten. Der rasche Zerfall wird dabei durch die Hilfsstoffauswahl (z.B. Brausesalze wie Natiumbicarbonat und Citronensäure) erreicht und der schlechte Geschmack des Wirkstoffes durch eine Umhüllung mit Polymeren verringert. Bei all diesen Systemen ist der Wirkstoff in eine rasch zerfallende Matrix eingearbeitet.Various solid dosage forms have therefore been developed, which quickly dissolve in the oral cavity (mouth saliva) and can then be swallowed without liquid. DE 27 44 493 C2 describes an administration form produced by lyophilization Tablet form with a porous matrix that dissolves in the mouth saliva within a few seconds. For this purpose, an autoclaved gelatin solution containing active ingredient is placed in preformed wells (for example a blister pack), frozen and dried by lyophilization in a porous matrix (tablet). DE 40 18 247 C2 describes rapidly disintegrating film-like dosage forms. US Pat. No. 5,762,961 and WO 93/13758 describe tablets which disintegrate rapidly due to their high porosity. The porosity is achieved by removing volatile auxiliaries after tableting. US Pat. No. 5,464,632 and US Pat. No. 5,178,878 describe rapidly disintegrating tablets which contain coated active ingredient particles. The rapid disintegration is achieved by the choice of excipients (eg effervescent salts such as sodium bicarbonate and citric acid) and the bad taste of the active ingredient is reduced by coating with polymers. In all of these systems, the active ingredient is incorporated into a rapidly disintegrating matrix.
Neben diesen Vorzügen weisen die beschriebenen rasch zerfallenden Darreichungsformen aber auch einige Nachteile auf, wie z.B. eine mangelnde mechanische Stabilität und eine hohe Feuchtigkeitsempfindlichkeit.In addition to these advantages, the rapidly disintegrating dosage forms described also have some disadvantages, such as lack of mechanical stability and high sensitivity to moisture.
Die durch Lyophilisation hergestellten Tabletten sind sehr zerbrechlich, sie können z.B. nicht aus einer Blisterpackung herausgedrückt werden, sondern müssen entnommen werden. Auch werden die tablettenartigen Darreichungsformen meist mit sehr geringer Härte hergestellt, um einen schnelleren Zerfall aufgrund der erhöhten Porosität zu ermöglichen oder um die Beschädigung überzogener Wirkstoffteilchen zu verringern.The tablets produced by lyophilization are very fragile, for example they cannot be pressed out of a blister pack, but have to be removed. Also, the tablet-like dosage forms are usually made with very low hardness in order to accelerate their disintegration To enable increased porosity or to reduce the damage to coated active ingredient particles.
Ferner sind die meisten rasch zerfallenden Darreichungsformen auch sehr feuchtigkeitsempfindlich und erfordern eine spezielle Verpackung.Furthermore, most rapidly disintegrating dosage forms are also very sensitive to moisture and require special packaging.
Aufgrund von verfahrenstechnischen und produktspezifischen Erfordernissen müssen häufig hohe Hilfsstoffmengen eingesetzt werden, diese Technologien sind daher für höher dosierte Wirkstoffe weniger geeignet .Due to process engineering and product-specific requirements, large quantities of excipients often have to be used; these technologies are therefore less suitable for higher-dose active ingredients.
Die Aufgabe dieser Erfindung war daher die Entwicklung einer rasch zerfallenden Darreichungsform, die viele der oben genannten Probleme vermeidet.The object of this invention was therefore to develop a rapidly disintegrating dosage form which avoids many of the problems mentioned above.
Die Aufgabe wird erfindungsgemäß dadurch gelöst, daß eine Kapsel zur Applikation von Wirkstoffen zur Verfügung gestellt wird, umfassend mindestens ein in wäßrigen Flüssigkeiten lösliches und/oder rasch zerfallendes Makromolekül oder eine Mischung aus mindestens zwei dieser Stoffe, wobei die Kapsel nach Applikation in Körperöffnungen rasch zerfällt.The object is achieved according to the invention in that a capsule for applying active substances is provided, comprising at least one macromolecule which is soluble and / or rapidly disintegrating in aqueous liquids, or a mixture of at least two of these substances, the capsule rapidly disintegrating into body openings after application .
Ferner wird die Aufgabe erfindungsgemäß dadurch gelöst, daß eine Kapsel zur oralen Applikation von Wirkstoffen zur Verfügung gestellt wird, wobei die Kapsel im Mund oder in der Mundhöhle rasch zerfällt .Furthermore, the object is achieved according to the invention in that a capsule for oral administration of active ingredients is made available, the capsule rapidly disintegrating in the mouth or in the oral cavity.
Ferner wird die Aufgabe erfindungsgemäß dadurch gelöst, daß eine Kapsel zur vaginalen, rektalen oder nasalen Applikation von Wirkstoffen zur Verfügung gestellt wird, wobei die Kapsel nach Einbringen in die Körperöffnung rasch zerfällt .Furthermore, the object is achieved in that a capsule for vaginal, rectal or nasal Application of active ingredients is provided, the capsule rapidly disintegrating after insertion into the body opening.
Ferner wird die Aufgabe erfindungsgemäß dadurch gelöst, daß eine Kapsel nach Einbringen in Körperöffnungen, die durch chirurgische Eingriffe oder Verletzungen entstanden sind, rasch zerfällt.Furthermore, the object is achieved in that a capsule quickly disintegrates after being introduced into body openings which have arisen as a result of surgical interventions or injuries.
Erfindungsgemäß ist das Makromolekül ausgewählt aus natürlichen und/oder synthetischen Polymeren, wie Proteinen und Peptiden, beispielsweise Gelatine, Albumin, Polysacchariden, beispielsweise Agar-Agar, Alginate, Carageen, Chitosan, Dextrin, Dextran, Pektin, Stärke und ihren Derivaten, Gummen, Cellulosederivaten, beispielsweise Hydroxypropylmethylcellulose , Hydroxypropylcellulose , Methylcellulose, Carboxymethylcellulose, Polyacrylate, nämlich Polyacrylsäure, Polyacrylamid, Polyethylenglykol , Polyvinylalcohol (auch teilhydrolysiert ) , Polyvinylpyrrolidon, Polyoxyethylenoxypropylen undAccording to the invention, the macromolecule is selected from natural and / or synthetic polymers, such as proteins and peptides, for example gelatin, albumin, polysaccharides, for example agar-agar, alginates, carageen, chitosan, dextrin, dextran, pectin, starch and their derivatives, gums, cellulose derivatives , for example hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, polyacrylates, namely polyacrylic acid, polyacrylamide, polyethylene glycol, polyvinyl alcohol (also partially hydrolyzed), polyvinyl pyrrolidone, polyoxyethylene oxypropylene and
Copolymere aus den genannten Verbindungen.Copolymers of the compounds mentioned.
Erfindungsgemäß bevorzugt ist eine Kapsel, wobei als weitere Hilfsstoffe eine oder mehrere Zerfallsbeschleuniger, Quellmittel (Quellstoffe) und/oder Lösungsvermittler oder deren Mischungen enthalten sind.A capsule is preferred according to the invention, one or more disintegrants, swelling agents (swelling agents) and / or solubilizers or mixtures thereof being contained as further auxiliaries.
Bevorzugt ist dabei, daß der Zerfallsbeschleuniger ausgewählt ist aus beispielsweise Brausesalzen, Zucker, Saccharose, Sorbitol, Mannitol , Saccharose. Erfindungsgemäß bevorzugt ist ferner, daß weitere Hilfsstoffe, nämlich Aromastoffe, Süßstoffe, Farbstoffe, Konservierungsmittel, Gelierungsmittel , Füllstoffe, Pigmente, Benetzungsmittel (Tenside) und Weichmacher enthalten sind.It is preferred that the disintegration accelerator is selected from, for example, effervescent salts, sugar, sucrose, sorbitol, mannitol, sucrose. It is also preferred according to the invention that further auxiliaries, namely flavorings, sweeteners, colorants, preservatives, gelling agents, fillers, pigments, wetting agents (surfactants) and plasticizers are contained.
Die erfindungsgemäße Kapsel ist ferner dadurch gekennzeichnet, daß die Kapselhülle Mikroporen aufweist.The capsule according to the invention is further characterized in that the capsule shell has micropores.
Bevorzugt ist es ferner, daß die Kapselhülle Hohlräume in Form von Gasblasen umschließt.It is further preferred that the capsule shell encloses cavities in the form of gas bubbles.
Erfindungsgemäß ist es vorgesehen, daß die erfindungsgemäße Kapsel in der Kapselhülle selbst einen Wirkstoff umfaßt.According to the invention, it is provided that the capsule according to the invention itself comprises an active ingredient in the capsule shell.
Erfindungsgemäß ist, daß das Wirkstoffhaltige Füllgut fest, halbfest oder flüssig ist .According to the invention, the active substance-containing filling is solid, semi-solid or liquid.
Erfindungsgemäß ist ferner, daß der Wirkstoff in retardierter Form vorliegt.It is also in accordance with the invention that the active substance is in retarded form.
Erfindungsgemäß ist ferner, daß der Wirkstoff in geschmacksmaskierter Form vorliegt.It is also in accordance with the invention that the active ingredient is present in taste-masked form.
Ein weiterer Gegenstand der vorliegenden Erfindung ist ein Arzneimittel, umfassend eine erfindungsgemäße Kapsel und eine darin enthaltene pharmazeutische Zubereitung, umfassend mindestens einen pharmazeutischen Wirkstoff und gegebenenfalls weitere pharmazeutisch verträgliche Hilfs- und Zusatzstoffe. Die erfindungsgemäße Aufgabe wurde also mit einer rasch zerfallenden kapselartigen Darreichungsform erreicht . Dabei wird z.B. das Wirkstoff/Hilfsstoffgemisch in eine rasch zerfallende Kapselhülle gefüllt. Die Kapsel zerfällt rasch oder löst sich rasch in der Mundhöhle auf/an, das feste oder flüssige Füllgut wird dann geschluckt . Rasch zerfallend ist ein weitgreifender Begriff und bedeutet, daß die Kapselhülle ihre Form nach Applikation in der Mundhöhle rasch verliert und rasch mit dem Füllgut geschluckt werden kann. Durch Bewegung der Kapsel (z.B. durch Zungenbewegung) kann der Zerfall positiv beeinflußt werden. Die Zerfallszeit beträgt wenige Minuten, bevorzugt jedoch weniger als 30 Sekunden.Another object of the present invention is a medicament comprising a capsule according to the invention and a pharmaceutical preparation contained therein, comprising at least one active pharmaceutical ingredient and, if appropriate, further pharmaceutically acceptable auxiliaries and additives. The object of the invention was therefore achieved with a rapidly disintegrating capsule-like dosage form. For example, the active ingredient / excipient mixture is filled into a rapidly disintegrating capsule shell. The capsule disintegrates quickly or quickly dissolves in the oral cavity, the solid or liquid contents are then swallowed. Rapidly disintegrating is a broad term and means that the capsule shell quickly loses its shape after application in the oral cavity and can be swallowed quickly with the contents. The disintegration can be positively influenced by moving the capsule (eg by moving the tongue). The disintegration time is a few minutes, but preferably less than 30 seconds.
Die erfindungsgemäße Kapsel weist eine Reihe von Vorteilen auf .The capsule according to the invention has a number of advantages.
Aufgrund der geringeren Hilfsstoffmengen können höhere Wirkstoffmengen und daher höher dosierte Wirkstoffe in Vergleich zu den oben bekannten Darreichungsformen des Standes der Technik verwendet werden.Because of the lower amounts of excipients, higher amounts of active ingredient and therefore higher dosed active ingredients can be used in comparison to the dosage forms of the prior art known above.
Viele Wirkstoffe haben einen schlechten Geschmack oder müssen retardiert freigesetzt werden und werden daher mit Polymerfilmen umhüllt. Beim Verpressen des umhüllten Arzneistoffes in Tabletten kann der Überzug beschädigt und damit seine Funktion verloren werden. Bei den durch Lyophilisation hergestellten Tabletten würde die Dispersion der überzogenen Wirkstoffteilchen in der wäßrigen Gelatinelösung vor der Lyophilisation die Auflösung der Hülle oder eine vorzeitige Freisetzung des Wirkstoffes hervorrufen.Many active ingredients have a bad taste or have to be released in a delayed manner and are therefore covered with polymer films. When the coated drug is compressed into tablets, the coating can be damaged and its function can be lost. In the case of the tablets produced by lyophilization, the dispersion of the coated active ingredient particles in the aqueous gelatin solution before the lyophilization would result in the disintegration of the shell or a premature release of the active ingredient cause.
Diese Probleme bestehen bei der kapselartigen Darreichungsform nicht, die überzogenen Wirkstoffpartikel werden z.B. keinen hohen Pressdrücken ausgesetzt.These problems do not exist with the capsule-like dosage form, the coated active ingredient particles are e.g. not exposed to high pressures.
Ferner sind auch die mechanischen Probleme und die Feuchtigkeitsempfindlichkeit reduziert/eliminiert .Furthermore, the mechanical problems and the sensitivity to moisture are also reduced / eliminated.
Das erfindungsgemäß verwendete Kapselmaterial kann jedes in wäßrigen Flüssigkeiten lösliches oder zerfallendes Material sein. Bevorzugt verwendet man dabei Makromoleküle, die sich rasch in Wasser auflösen oder zerfallen. Dazu zählen sowohl natürliche als auch synthetische Polymere, wie Proteine/Peptide (z.B. Gelatine, Albumin), Polysaccharide (z.B. Agar-Agar, Alginate, Carageen, Chitosan, Dextrin, Dextran, Pektin, Stärke und ihre Derivate, Gummen natürlicher Herkunft) Cellulosederivate (z.B. Hydroxypropylmethylcellulose , Hydroxypropylcellulose , Methylcellulose, Carboxymethylcellulose) , Polyacrylate (z.B. Polyacrylsäure, Polyacrylamid) , Polyethylenglykol , Polyvinylalcohol (auch teilhydrolysiert) ,The capsule material used according to the invention can be any material which is soluble or disintegrating in aqueous liquids. Macromolecules which dissolve or disintegrate rapidly in water are preferably used. These include both natural and synthetic polymers, such as proteins / peptides (e.g. gelatin, albumin), polysaccharides (e.g. agar-agar, alginates, carageen, chitosan, dextrin, dextran, pectin, starch and their derivatives, gums of natural origin) cellulose derivatives ( e.g. hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose), polyacrylates (e.g. polyacrylic acid, polyacrylamide), polyethylene glycol, polyvinyl alcohol (also partially hydrolyzed),
Polyvinylpyrrolidon, Polyoxyethylenoxypropylen und auch entsprechende Copolymere .Polyvinylpyrrolidone, polyoxyethyleneoxypropylene and also corresponding copolymers.
Bei Polymeren spielt die Molmasse eine wichtige Rolle, Kapselmaterialien mit niedriger Molmasse zerfallen oder lösen sich in der Regel schneller. Ferner können höherkonzentrierte flüssige Systeme mit den niedermolekularen Oligo- /Polymeren hergestellt werden. Die Molmasse der Polymere kann z.B. durch hydrolytischen oder enzymatischen Abbau reduziert werden. Bei einigen Polymeren (z.B. Gelatine) kann die Molmasse z.B. durch Erhitzen (z.B. Autoklavieren) verringert werden.Molecular weight plays an important role in the case of polymers; capsule materials with a low molecular weight disintegrate or usually dissolve more quickly. Higher concentration liquid systems can also be produced with the low molecular weight oligomers / polymers. The molecular weight of the polymers can be determined, for example, by hydrolytic or enzymatic degradation can be reduced. In the case of some polymers (eg gelatin) the molecular weight can be reduced, for example, by heating (eg autoclaving).
Die Kapselmaterialien können auch in Kombination verwendet werden.The capsule materials can also be used in combination.
Zur Beeinflussung des Zerfalls können schnell zerfallende/schnell auflösende Hilfsstoffe (z.B. Zerfallsmittel wie Brausesalz oder Zucker und Zuckerderivate wie z.B. Sorbitol, Mannitol, Mannit , Sorbit, Saccharose) in die Kapselhülle eingearbeitet werden. Der Zerfall kann auch durch die Porosität der Kapselhülle beeinflußt werden. Gasblasen können in die Kapselhülle zur Erhöhung der Porosität und damit zur Beschleunigung des Zerfalls während der Kapselhüllenherstellung (z.B. Dispersion von Gas in die Flüssigkeit beim Eintauchverfahren) eingearbeitet werden. Alternativ können flüchtige Bestandteile in die Kapselhülle während der Herstellung eingearbeitet werden, die nach ihrem Entfernen eine poröse Kapselhülle ergeben.Rapidly disintegrating / rapidly dissolving auxiliaries (e.g. disintegrants such as effervescent salt or sugar and sugar derivatives such as sorbitol, mannitol, mannitol, sorbitol, sucrose) can be incorporated into the capsule shell to influence disintegration. Decay can also be affected by the porosity of the capsule shell. Gas bubbles can be incorporated into the capsule shell to increase the porosity and thus to accelerate the disintegration during the capsule shell production (e.g. dispersion of gas in the liquid during the immersion process). Alternatively, volatile components can be incorporated into the capsule shell during manufacture, which, when removed, result in a porous capsule shell.
Ferner können weitere Hilfsstoffe in die Kapselhülle eingearbeitet werden. Dazu zählen z.B. Aromastoffe, Süßstoffe, Farbstoffe, Konservierungsmittel, Gelierungsmittel (zur unterstützenden Bildung der Kapselhülle, z.B. beim Eintauchverfahren), Füllstoffe, Pigmente, Benetzungsmittel (Tenside) und Weichmacher. Die Kapseln können auch mit einer dünnen Schicht überzogen werden, die z.B. die Feuchtigkeitsempfindlichkeit herabsetzt oder den Speichelfluß positiv beeinflußt. Der Wirkstoff (auch in "behandelter Form" z.B Mikro- /Nanopartikel) kann auch während der Kapselherstellung direkt in die rasch zerfallende Kapselhülle eingearbeitet werden, die Kapsel kann dann entweder mit Füllgut gefüllt oder auch nicht gefüllt werden.Further auxiliary substances can also be incorporated into the capsule shell. These include, for example, flavorings, sweeteners, colorants, preservatives, gelling agents (to support the formation of the capsule shell, for example during the immersion process), fillers, pigments, wetting agents (surfactants) and plasticizers. The capsules can also be coated with a thin layer which, for example, reduces sensitivity to moisture or has a positive effect on the flow of saliva. The active ingredient (also in "treated form", for example micro / nanoparticles) can also be incorporated directly into the rapidly disintegrating capsule shell during capsule production, the capsule can then either be filled with filling material or not.
Das Füllgut der Kapsel (Kapselinhalt) enthält den Wirkstoff und, falls erforderlich, verschiedene Hilfsstoffe. Das Füllgut kann fest, halbfest oder flüssig sein.The contents of the capsule (capsule content) contain the active ingredient and, if necessary, various auxiliary substances. The contents can be solid, semi-solid or liquid.
Die erfindungsgemäßen Darreichungsformen werden normalerweise für Wirkstoffe verwendet, die im Magen-Darm Kanal resorbiert werden oder lokal wirken. Eine Resorption oder lokale Wirkung in der Mundhöhle ist jedoch auch möglich.The dosage forms according to the invention are normally used for active substances which are absorbed in the gastrointestinal tract or which act locally. However, absorption or local effects in the oral cavity is also possible.
Neben der oralen Anwendung kann die Kapsel auch in anderen Körperöffnungen angewendet werden. Dazu zählen insbesondere der vaginale, rektale, nasale Applikationsweg und auch durch chirurgische Eingriffe oder Verletzungen entstandene Körperöffnunge .In addition to oral use, the capsule can also be used in other body openings. This includes in particular the vaginal, rectal, nasal route of application and also body openings caused by surgical interventions or injuries.
Die erfindungsgemäßen Darreichungsformen können zur Verabreichung einer Vielzahl von Wirkstoffen oder Wirkstoffkombinationen verwendet werden. Mögliche Arzneistoffe sind in dem Lehrbuch der Pharmakologie und Toxikologie "Arzneimittelwirkungen" von E. Mutschier, Wissenschaftliche Verlagsgesellschaf mbH aufgeführt.The dosage forms according to the invention can be used for the administration of a large number of active substances or combinations of active substances. Possible drugs are listed in the textbook of pharmacology and toxicology "drug effects" by E. Mutschier, Wissenschaftliche Verlagsgesellschaftsch mbH.
Ein besonderer Aspekt der Erfindung ist, daß der Wirkstoff in retardierter Form vorliegen kann. Der Wirkstoff kann z.B. in Pellets (Matrix- der Reservoirpellets), Mikropartikel (z.B. Mikrosphärulen oder Mikrokapseln) oder kolloidale Teilchen (z.B. Nanopartikel , Liposomen) eingearbeitet sein. Dabei können unterschiedliche retardierende Materialien eingesetzt werden, z.B. Polymere mit pH-abhängiger Löslichkeit (z.B. magensaftresistente Polymere) oder in Magen-Darmsaft unlösliche Polymere (z.B. Cellulosederivate, Acrylatderivate, Polyester) oder bioabbaubare Polymere (z.B. Poly (lactid-co-glycolide) oder Lipide .A special aspect of the invention is that the active ingredient may be in a delayed form. The active ingredient can, for example, be incorporated into pellets (matrix or reservoir pellets), microparticles (eg microsphere or microcapsules) or colloidal particles (eg nanoparticles, liposomes). Different retarding materials can be used, e.g. polymers with pH-dependent solubility (e.g. enteric polymers) or polymers insoluble in gastrointestinal juice (e.g. cellulose derivatives, acrylate derivatives, polyester) or biodegradable polymers (e.g. poly (lactide-co-glycolide) or lipids .
Viele Wirkstoffe haben einen schlechten Geschmack oder Geruch. Zur Umgehung dieses Problems können dem Füllgut entsprechende Zusätze beigegeben werden oder der Wirkstoff kann umhüllt oder an Ionenaustauscherharz gebunden sein.Many active ingredients have a bad taste or smell. In order to circumvent this problem, appropriate additives can be added to the filling material or the active ingredient can be coated or bound to ion exchange resin.
Falls erforderlich kann die Wirkstoffauflösung durch bekannte galenische Verfahren verbessert werden (z.B. Auflösen in einem geeigneten Lösungsmittel, Einbettung in Trägermaterialen, Verringerung der Teilchengröße durch physikalische oder chemische Verfahren - auch Nanoteilchen, Nanokristalle, Verkapselung in kolloidale Trägerteilchen, wie z.B. Liposomen, Lipid- oder Polymernanopartikel) und der Wirkstoff in dieser Form dem Füllgut beigeben oder eingearbeitet werden.If necessary, the active ingredient dissolution can be improved by known galenic methods (e.g. dissolving in a suitable solvent, embedding in carrier materials, reducing the particle size by physical or chemical methods - also nanoparticles, nanocrystals, encapsulation in colloidal carrier particles, such as liposomes, lipid or polymer nanoparticles ) and the active ingredient is added or incorporated into the product in this form.
Außer Arzneistoffen kann die erfindungsgemäßeIn addition to drugs, the invention
Darreichungsform auch für Süßwaren, Lebensmittel (u.a. Vitamine, Mineralstoffe) und Kosmetika (z.B. zurDosage form also for confectionery, food (e.g. vitamins, minerals) and cosmetics (e.g. for
Mundhygiene) zur oralen Anwendung oder Einnahme eingesetzt werden .Oral hygiene) used for oral use or ingestion become .
Das Füllgut kann sowohl fest, als auch halbfest oder flüssig sein. Der Wirkstoff oder der wie oben beschriebene verarbeitete Wirkstoff kann in einer Flüssigkeit gelöst und/oder dispergiert werden und dann in flüssiger Form in die Kapsel abgefüllt werden. Das feste Füllgut kann in Pulver-oder Granulatform vorliegen oder auch in Form kleiner Tabletten oder Pellets oder rasch zerfallender Matrixsysteme.The contents can be solid, semi-solid or liquid. The active ingredient or the active ingredient processed as described above can be dissolved and / or dispersed in a liquid and then filled into the capsule in liquid form. The solid filling material can be in powder or granule form or also in the form of small tablets or pellets or rapidly disintegrating matrix systems.
Das Füllgut kann neben dem Wirkstoff auch Hilfsstoffe erhalten. Dazu zählen z.B. Geschmacksmittel, Aromastoffe, Süßstoffe, Zerfallsmittel, Benetzungsmittel, Farbstoffe, Fließregulierungsmittel, Füllstoffe, Bindemittel. Auch ein Brausesatz kann zum schnelleren Zerfall des Kapselinhalts oder zur Geschmacksverbesserung und Anregung des Speichelflusses verwendet werden. Es können auch dem Fachmann bekannte Hilfsstoffe beigegeben werden, die das Mundgefühl der Darreichungsform verbessern.In addition to the active ingredient, the contents can also contain auxiliary substances. These include e.g. Flavors, flavors, sweeteners, disintegrants, wetting agents, colorants, flow regulators, fillers, binders. An effervescent set can also be used to help the capsule contents disintegrate more quickly or to improve taste and stimulate salivation. Auxiliaries known to the person skilled in the art can also be added, which improve the mouthfeel of the dosage form.
Gegenstand der Erfindung sind auch Verfahren zur Herstellung der erfindungsgemäßen Darreichungsform. Die Kapselhüllen können durch bekannte Kapselherstellverfahren, analog der Herstellung von Weich- oder Hartkapseln hergestellt werden. Dazu zählt z.B. das Eintauchverfahren, bei dem kapseiförmige Metallstifte in eine Flüssigkeit, welche die Kapselmaterialien/Hilfsstoffe enthält, eintaucht, die Flüssigkeit an der Stiftoberfläche festhält und nach Trocknung die Kapselhüllen erhalten werden. Die Kapselmaterialien und weitere Hilfsstoffe werden dazu in einem Lösungsmittel oder Lösemittelgemischen (bevorzugt wasserhaltig) gelöst bzw. dispergiert. Bei schmelzenden Kapselhüllmaterialien können die Kapselhüllen auch durch Eintauchen der Stifte in die Schmelze und anschließendes Abkühlen hergestellt werden. Die Größe und Form der Kapselhülle wird durch die Größe und Form der Stifte mitbestimmt .The invention also relates to processes for producing the dosage form according to the invention. The capsule shells can be produced by known capsule production methods, analogous to the production of soft or hard capsules. This includes, for example, the immersion process, in which capsule-shaped metal pins are immersed in a liquid which contains the capsule materials / auxiliary substances, the liquid adheres to the surface of the pin and the capsule shells are obtained after drying. The capsule materials and other auxiliary substances are described in a solvent or solvent mixture (preferably containing water) dissolved or dispersed. In the case of melting capsule shell materials, the capsule shells can also be produced by immersing the pins in the melt and then cooling them. The size and shape of the capsule shell is determined by the size and shape of the pins.
In einem anderen Verfahren werden die Kapseln mittels Spritzgußverfahren, bei denen die Kapselmasse in vorgeformte Formen eingeben wird, hergestellt.In another method, the capsules are manufactured by means of injection molding, in which the capsule mass is introduced into preformed forms.
Die Kapseln können durch die dem Fachmann bekannte Verfahren mit dem Füllgut befüllt und verschlossen werden.The capsules can be filled with the contents and sealed by the process known to the person skilled in the art.
Beispiele für die in dieser Erfindung verwendbarenExamples of those usable in this invention
Makromoleküle, Hilfsstoffe, Füllgüter und Verfahren können neben der Fachliteratur auch in entsprechenden LehrbüchernMacromolecules, auxiliaries, filling materials and processes can be found in the corresponding literature as well as in the corresponding textbooks
(z.B. Modern Pharmaceutics, Marcel Dekker; Pharmaceutical Dosage Forms : Tablets, Band 1-3, Marcel Dekker; The Theory and Practice of Industrial Pharmacy, Lea&Febiger ; Pharmazeutische Technologie, Thieme-Verlag; Pharmazeutische Technologie, Fischer-Verlag; Die Kapsel; APV Paperback, Wissenschaftliche Verlagsgesellschaft mbH) gefunden werden.(e.g. Modern Pharmaceutics, Marcel Dekker; Pharmaceutical Dosage Forms: Tablets, Volume 1-3, Marcel Dekker; The Theory and Practice of Industrial Pharmacy, Lea &Febiger; Pharmaceutical Technology, Thieme-Verlag; Pharmaceutical Technology, Fischer-Verlag; Die Kapsel; APV Paperback, Wissenschaftliche Verlagsgesellschaft mbH) can be found.
Die folgenden Beispiele erläutern die Erfindung:The following examples illustrate the invention:
Beispiel 1example 1
Kapseiförmige Tauchstifte (Kapselgröße 00) wurden in eine erwärmte autoklavierte Gelatinelösung (20-40%) , in derCapsule-shaped dip sticks (capsule size 00) were placed in a heated, autoclaved gelatin solution (20-40%) in the
Glycerol und Sorbitol aufgelöst wurde, eingetaucht und wieder herausgezogen. Nach Trocknung wurden die Kapselhälften abgezogen, geschnitten und zusammengesteckt. Die Kapselhüllen zerfielen in der Mundhöhle in weniger als 30 sec.Glycerol and sorbitol was dissolved, immersed and pulled out again. After drying, the capsule halves were pulled off, cut and put together. The capsule shells disintegrated in the oral cavity in less than 30 seconds.
Beispiel 2Example 2
Kapseiförmige Tauchstifte (Kapselgröße 00) wurde in eine autoklavierte Gelatinelösung (20-40%) , in der Glycerol und Sorbitol aufgelöst wurde und feine Luftblasen diespergiert wurden, eingetaucht und wieder herausgezogen. Nach Trocknung wurde die Kapselhälften abgezogen, geschnitten, und zusammengesteckt. Die Kapselhüllen zerfielen in der Mundhöhle in weniger als 30 sec.Capsule-shaped dip sticks (capsule size 00) were immersed in an autoclaved gelatin solution (20-40%) in which glycerol and sorbitol were dissolved and fine air bubbles were dispersed, and pulled out again. After drying, the capsule halves were peeled off, cut, and put together. The capsule shells disintegrated in the oral cavity in less than 30 seconds.
Beispiel 3Example 3
Die nach Beispiel 1 oder 2 hergestellten Kapseln wurden mit einem Gemisch aus Laktose und mikroverkapselten Paracetamol (geschmacksmaskiert, mit Ethylcellulose überzogen) vor dem Zusammenstecken der Kapselhüllen befüllt. Die Kapseln zerfielen in der Mundhöhle in weniger als 30 sec.The capsules produced according to Example 1 or 2 were filled with a mixture of lactose and microencapsulated paracetamol (taste masked, coated with ethyl cellulose) before the capsule shells were put together. The capsules disintegrated in the oral cavity in less than 30 seconds.
Beispiel 4Example 4
Die nach Beispiel 1 oder 2 hergestellten Kapseln wurden mit einem Gemisch aus mikrokristalliner Cellulose, Brausesalz und Propranolol HCl Retardpellets (mit Ethylcellulose überzogen) vor dem Zusammenstecken der Kapselhüllen befüllt. Die Kapseln zerfielen in der Mundhöhle in weniger als 30 sec. The capsules produced according to Example 1 or 2 were filled with a mixture of microcrystalline cellulose, effervescent salt and propranolol HCl sustained release pellets (coated with ethyl cellulose) before the capsule shells were put together. The capsules disintegrated in the oral cavity in less than 30 seconds.

Claims

Patentansprüche claims
1. Kapsel zur Applikation von Wirkstoffen, umfassend mindestens ein in wäßrigen Flüssigkeiten lösliches und/oder rasch zerfallendes Makromolekül oder eine Mischung aus mindestens zwei dieser Stoffe, wobei die Kapsel nach Applikation in Körperöffnungen rasch zerfällt .1. capsule for application of active substances, comprising at least one macromolecule soluble and / or rapidly disintegrating in aqueous liquids or a mixture of at least two of these substances, the capsule rapidly disintegrating into body openings after application.
2. Kapsel gemäß Anspruch 1 zur oralen Applikation von Wirkstoffen, wobei die Kapsel im Mund oder in der Mundhöhle rasch zerfällt.2. Capsule according to claim 1 for oral administration of active ingredients, the capsule rapidly disintegrating in the mouth or in the oral cavity.
3. Kapsel gemäß Anspruch 1 zur vaginalen, rektalen oder nasalen Applikation von Wirkstoffen, wobei die Kapsel nach Einbringen in die Körperöffnung rasch zerfällt.3. Capsule according to claim 1 for vaginal, rectal or nasal application of active ingredients, the capsule rapidly disintegrating after insertion into the body opening.
4. Kapsel gemäß Anspruch 1, wobei die Kapsel nach Einbringen in Körperöffnungen, die durch chirurgische4. Capsule according to claim 1, wherein the capsule after insertion into body openings by surgical
Eingriffe oder Verletzungen entstanden sind, rasch zerfällt .Interventions or injuries occurred, quickly disintegrated.
5. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß das Makromolekül ausgewählt ist aus natürlichen und/oder synthetischen Polymeren, Proteinen, Peptiden, nämlich Gelatine, Albumin, Polysacchariden, nämlich Agar-Agar, Alginate, Carageen, Chitosan, Dextrin, Dextran, Pektin, Stärke und ihren Derivaten, Gummen, Cellulosederivaten, nämlich Hydroxypropylmethylcellulose , Hydroxypropylcellulose , Methylcellulose, Carboxymethylcellulose, Polyacrylate, nämlich Polyacrylsäure, Polyacrylamid,5. Capsule according to one of the preceding claims, characterized in that the macromolecule is selected from natural and / or synthetic polymers, proteins, peptides, namely gelatin, albumin, polysaccharides, namely agar-agar, alginates, carageen, chitosan, dextrin, dextran , Pectin, starch and their derivatives, gums, cellulose derivatives, namely hydroxypropylmethyl cellulose, hydroxypropyl cellulose, Methyl cellulose, carboxymethyl cellulose, polyacrylates, namely polyacrylic acid, polyacrylamide,
Polyethylenglykol, Polyvinylalcohol (auch teilhydrolysiert) , Polyvinylpyrrolidon, Polyoxyethylenoxypropylen und Copolymere aus den genannten Verbindungen.Polyethylene glycol, polyvinyl alcohol (also partially hydrolyzed), polyvinyl pyrrolidone, polyoxyethylene oxypropylene and copolymers from the compounds mentioned.
6. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß als weitere Hilfsstoffe ein oder mehrere Zerfallsbeschleuniger, Quellmittel (Quellstoffe) und/oder Lösungsvermittler oder deren Mischungen enthalten sind.6. Capsule according to one of the preceding claims, characterized in that one or more disintegrants, swelling agents (swelling agents) and / or solubilizers or mixtures thereof are contained as further auxiliaries.
7. Kapsel gemäß Anspruch 9, dadurch gekennzeichnet, daß der Zerfallsbeschleuniger ausgewählt ist aus7. Capsule according to claim 9, characterized in that the decay accelerator is selected from
Brausesalzen, Zucker, Zuckerderivaten, Saccharose, Sorbitol, Mannitol .Effervescent salts, sugar, sugar derivatives, sucrose, sorbitol, mannitol.
8. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß weitere Hilfsstoffe, nämlich Aromastoffe, Süßstoffe, Farbstoffe, Konservierungsmittel, Gelierungsmittel , Füllstoffe, Pigmente, Benetzungsmittel (Tenside) und Weichmacher enthalten sind.8. Capsule according to one of the preceding claims, characterized in that it contains further auxiliaries, namely flavorings, sweeteners, colorants, preservatives, gelling agents, fillers, pigments, wetting agents (surfactants) and plasticizers.
9. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß die Kapselhülle Mikroporen aufweist .9. Capsule according to one of the preceding claims, characterized in that the capsule shell has micropores.
10. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß die Kapselhülle Hohlräume in Form von Gasblasen umschließt.10. Capsule according to one of the preceding claims, characterized in that the capsule shell cavities encloses in the form of gas bubbles.
11. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß die Kapselhülle selbst einen Wirkstoff umfaßt.11. Capsule according to one of the preceding claims, characterized in that the capsule shell itself comprises an active ingredient.
12. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß das Wirkstoffhaltige Füllgut fest, halbfest oder flüssig ist.12. Capsule according to one of the preceding claims, characterized in that the active substance-containing filling is solid, semi-solid or liquid.
13. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß der Wirkstoff in retardierter Form vorliegt.13. Capsule according to one of the preceding claims, characterized in that the active ingredient is in retarded form.
14. Kapsel gemäß einem der voranstehenden Ansprüche, dadurch gekennzeichnet, daß der Wirkstoff in geschmacksmaskierter Form vorliegt.14. Capsule according to one of the preceding claims, characterized in that the active ingredient is in taste-masked form.
15. Arzneimittel, umfassend eine Kapsel gemäß einem der voranstehenden Ansprüche und eine darin enthaltene pharmazeutische Zubereitung, umfassend mindestens einen pharmazeutischen Wirkstoff und gegebenenfalls weitere verträgliche Hilfs- und Zusatzstoffe. 15. Medicament, comprising a capsule according to one of the preceding claims and a pharmaceutical preparation contained therein, comprising at least one pharmaceutical active ingredient and optionally further compatible auxiliaries and additives.
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EP1178777A2 (en) 2002-02-13

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