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WO2000025744A1 - Composition pharmaceutique coulante en granules et forme galenique sous forme de paille pour administration orale - Google Patents

Composition pharmaceutique coulante en granules et forme galenique sous forme de paille pour administration orale Download PDF

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Publication number
WO2000025744A1
WO2000025744A1 PCT/US1999/025454 US9925454W WO0025744A1 WO 2000025744 A1 WO2000025744 A1 WO 2000025744A1 US 9925454 W US9925454 W US 9925454W WO 0025744 A1 WO0025744 A1 WO 0025744A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
oral administration
straw
medicament
dosage form
Prior art date
Application number
PCT/US1999/025454
Other languages
English (en)
Inventor
Joseph M. Morris
James S. Beahm
Original Assignee
Mcneil-Ppc, Inc.
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 Mcneil-Ppc, Inc. filed Critical Mcneil-Ppc, Inc.
Priority to AU12408/00A priority Critical patent/AU1240800A/en
Priority to JP2000579188A priority patent/JP2002528483A/ja
Priority to CA002348024A priority patent/CA2348024C/fr
Publication of WO2000025744A1 publication Critical patent/WO2000025744A1/fr

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
    • A61K9/0012—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol

Definitions

  • This invention relates to granular, free-flowing, pleasant tasting pharmaceutical compositions for oral administration, and also to straw-like dosage forms for administering same. These forms permit a more convenient and reliable way of administering a wide variety of medicaments and nutrients to those having difficulty in using other types of oral dosage forms.
  • Orally administered medicaments exist in many forms such as liquid solutions, emulsions, suspensions, capsules and tablets. Caplet and tablet forms are generally intended to be swallowed whole. Therefore, the often disagreeable taste of the medicament need not be taken into account when formulating such medicine, except in preventing any unpleasant taste while the medicine is in the mouth. This can be accomplished by placing a thin and quickly dissolving coating on the tablet, by using the gelatin capsule form, or by firmly compressing a tablet during manufacture so as to prevent its disintegration while in the mouth.
  • a common problem with chewable tablet forms is the often disagreeable taste of the active ingredient which manifests itself during chewing.
  • the taste of the medicament in a tablet can be overpowered by adding flavoring ingredients to the tablet so that when it is chewed, the taste of the medicament is simply overpowered. This has been done, for example, with children' s aspirin, where the dosage is small enough so that the amount of flavoring agents needed to mask the taste of the medicament is not so great that the tablet becomes unreasonably large.
  • acetaminophen is present in granules coated with polymers such as ethyl cellulose, or cellulose acetate and polyvinyl pyrrolidone. While the tablet is in the mouth, a significant proportion of the acetaminophen remains shielded by the coating and thus does not contribute to taste, despite some breakage of the polymer coating upon compression of the tablet during manufacture, and additional breakage of the coating during chewing. The acetaminophen becomes bioavailable from the granules where the coating is broken, and from permeation through the coating.
  • ethylcellulose films are water- permeable, and combination films, such as cellulose acetate and polyvinyl pyrrolidone, contain one soluble component which dissolves in the gastrointestinal tract, rendering the film permeable to water and dissolved active components.
  • This invention provides a dry, granular, free- flowing, stable pharmaceutical composition for oral administration comprising particles of medicament or nutrient coated with a suitable taste-masking agent, a salivation-inducing agent, and a pharmaceutically acceptable carrier.
  • This invention also provides a dosage form -for oral administration comprising a closed, moisture- resistant, straw-like container having therein a single unit dose of the instant pharmaceutical composition, and having an opening means for permitting the dry oral administration thereof.
  • this invention provides a dosage form for oral administration comprising a closed, moisture- resistant, non-straw-like container having therein a single unit dose of the instant pharmaceutical composition, and having an opening means for permitting the dry oral administration thereof.
  • Figure 1 shows examples of the instant dosage forms, i.e., a straw dosage form, a pouch dosage form, and a blister pack dosage form.
  • This invention provides dry, granular, free-flowing, stable, pleasant tasting pharmaceutical compositions for oral administration.
  • the invention also provides dosage forms employing both straw-like and non-straw-like containers for administering same. These forms are a convenient and reliable way of administering a wide variety of medicaments and nutrients to those having difficulty using other types of oral dosage forms,- especially tablets and capsules.
  • this invention provides a dry, granular, free-flowing, stable pharmaceutical composition for oral administration comprising particles of medicament or nutrient coated with a suitable taste-masking agent, a salivation-inducing agent, and a pharmaceutically acceptable carrier.
  • the instant dry composition has a total water content of less than 10% by weight. In the preferred embodiment, the instant dry composition has a total water content of less than 3% by weight.
  • stable shall mean physically as well as chemically stable. This term is well understood in the art and includes, but is not limited to, having a shelf life of at least about two years.
  • the medicament or nutrient used in this invention can be any medicament or nutrient suitable for ⁇ oral administration.
  • the types of medicaments envisioned for use in this invention include, without limitation, analgesics, antacids, antibiotics, decongestants, antitussives, expectorants, local anaesthetics, antihistamines, sympathomimetics, laxatives, and antidiarrheals.
  • the types of nurients envisioned for use in this invention include, without limitation, minerals such as iron, and vitamins such as B «, B 12 thiamin and folic acid.
  • analgesics include, by way of example, acetaminophen, acetyl salicylic acid, indomethacin and optically active isomers or racemates of ibuprofen, naproxen, flurbiprofen, carprofen, tiaprofenic acid, cicloprofen, ketoprofen, ketorolac, etodolac, indomethacin, sulindac, fenoprofen, diclofenac, piroxicam, benzydomine, nabumetone, their pharmaceutically acceptable salts and mixtures thereof.
  • the analgesic is acetaminophen.
  • Decongestants for use in the present invention include, for example, pseudoephedrine, phenylpropanolamine, phenylephrine and ephedrine, their pharmaceutically acceptable salts, and mixtures thereof.
  • Antitussives for use in this invention- include, for example, dextromethorphan, chlophedianol, carbetapentane, caramiphen, noscapine, diphenhydramine, codeine, hydrocodone, hydromorphone, fominoben, benzonatate, their pharmaceutically acceptable salts, and mixtures thereof.
  • Expectorants also known as ucolytic agents
  • glyceryl guaiacolate guaifenesin, terpin hydrate, ammonium chloride, N-acetylcysteine and bromhexine, ambroxol, their pharmaceutically acceptable salts, and mixtures thereof.
  • Local anaesthetics useful in this invention include, for example, hexylresorcinol, dyclonine, benzocaine, phenol, their pharmaceutically acceptable salts, and mixtures thereof.
  • Antihistamines useful in the present invention include, for example, chlorpheniramine, brompheniramine, diphenhydramine, dexchlorpheniramine, dexbromphreniramine, triprolidine, azatadine, doxylamine, tripelennamine, cyproheptadine, hydroxyzine, carbinoxamine, pheninda ine, bromodiphenhydramine, pyrilamine, their pharmaceutically acceptable salts and mixtures thereof, as well as the non-sedating antihistamines such as acrivastine, AHR-11325, astemizole, azatadine, azelastine, cetirizine, ebastine, ketotifen, lodoxamide, loratidine, levocabastine, mequitazine, oxatomide, setastine, tazifylline, warmthlastine, and terfenadine, their pharmaceutically acceptable salts and mixtures thereof.
  • Sympathomimetics suitable for use in this invention include, for example, pseudoephedrine, phenylpropanolamine, pharmaceutically acceptable salts thereof (e.g., pseudoephedrine hydrochloride) , and mixtures thereof.
  • Laxatives which can be used in the present invention include, for example, sennosides A and B.
  • Suitable antidiarrheals include, for example, loperamide and pharmaceutically acceptable salts thereof (e.g., loperamide HC1) .
  • salts refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts derived from inorganic bases include sodium, potassium, lithium, ammonia, calcium, magnesium, ferrous, zinc, manganous, aluminum, ferric, manganic salts and the like.
  • Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, tertiary and quaternary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins such as triethylamine, tripropylamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, amino acids generally and lysine, arginine and histidine specifically, caffeine, procaine, N-ethylpiperidine, hydraba ine, choline-, betaine, ethylenediamine, glucosamine, methylglycamine, theobromine, purines, piperazine, piperidine, polyamine resins and the like.
  • basic ion exchange resins such as triethylamine, tripropylamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, amino acids generally and lysine, arginine and histidine specifically, caffeine, procaine
  • taste-masking agents include, for example, ethyl cellulose ("EC”); cellulose acetate (“CA”); cellulose acetate butyrate (“CAB”) ; polymethacrylates such as dimethylaminoethyl methacrylate and neutral methacrylic acid ester (Eudragit ® E-100) ; hydroxypropyl cellulose (“HPC”) ; hydroxyethyl cellulose (“HEC”) ; and hydroxypropyl methyl cellulose (“HPMC”) .
  • medicament particles that are already taste-masked can be purchased commercially.
  • taste-masked acetaminophen particles are commercially available from Eurand America, Inc. (845 Center Drive, Vandalia, OH 45377) , and taste-masked pseudoephedrine ("PE”) and chlorpheniramine maleate
  • CPM Particle Dynamics, Inc. (2503 South Hanley Road, St. Louis, MO 63144J .
  • Pharmaceutically acceptable carriers are generally water-disintegratable carbohydrates which are described in Lieberman et al., Pharmaceutical Dosage Forms (Marcel Dekker, Inc., New York, 2 Ed. Vol. 1, pp. 205- 209 (1990) ) .
  • Preferred carriers include dextrose, sucrose, lactose, maltose, xylose, maltodextrins, dextrates, mannitol, sorbitol, and xylitol.
  • salivation-inducing agents are appropriate for the proper ingestion of the instant pharmaceutical composition, given its dry, granular nature. Such agents are routinely used in the art, and are usually carboxylic acids.
  • the salivation-inducing agent is an edible carboxylic acid such as citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, or adipic acid.
  • anhydrous carboxylic acids are used. The use of carboxylic acids in specific formulations is shown in the Examples section below.
  • the instant pharmaceutical composition ideally includes components additional to the medicament, salivation-inducing agent, and carrier.
  • the pharmaceutical composition further comprises one or more of a soothing agent, a sweetener, and a flavoring agent.
  • the composition comprises all of these additional components.
  • Soothing agents create a "cooling" sensation in the mouth due to their negative heat of hydration.
  • These are widely used in the art and include, for - example, mannitol, sorbitol, and xylitol.
  • Suitable sweeteners include, for example, aspartame, sucralose, saccharine, cyclamate, acesulfame potassium, manitol, sorbitol, and xylitol.
  • Suitable flavoring agents include, for example, fruit flavoring (e.g. lemon flavor) and cream flavoring.
  • a more extensive list of soothing agents, sweeteners, and flavoring agents is provided in Handbook of Pharmaceutical Excipients, 2 nd ed. (American Pharmaceutical Association, Washington, D.C. (1994) ) .
  • the pharmaceutical composition comprises coated acetaminophen particles, citric acid, mannitol, a sweetener, and lemon flavoring. Additional, more specific embodiments of this composition are provided in the Examples section below.
  • the coated particles of the instant pharmaceutical composition comprise a plurality of medicaments and/or nutrients.
  • the composition has one type of coated particle containing a plurality of medicaments and/or nutrients, and (ii) the composition has more than one type of coated particle, each type containing a one or more medicaments and/or nutrients.
  • the composition comprises coated acetaminophen particles and coated particles of either chlorpheniramine maleate or pseudoepheddrine (Descote ® , Particle Dynamics, Inc.). This invention also provides two dosage forms for oral administration.
  • the first form comprises a closed, moisture-resistant, straw-like container having therein a single unit dose of the instant pharmaceutical composition, and having an opening means for permitting the dry oral administration thereojf.
  • the second form comprises a closed, moisture-resistant, non-straw-like container having therein a single unit dose of the instant pharmaceutical composition, and having an opening means for permitting the dry oral administration thereof.
  • dry oral administration means oral administration that does not require the concomitant intake of water or other liquid.
  • the coated medicament is acetaminophen, whose single unit dosages include, for example, 50 mg, 80 mg, 160 mg, 300 mg, 325 mg, 500 mg and 1000 mg.
  • the term "straw-like container” means any container having a cylindrical shape whose length is greater than its width.
  • the dimensions of the straw-like container used in this invention can vary widely. In one embodiment, its dimensions are those of an ordinary drinking straw, e.g., having a length of about 200 mm and a width of about 6 mm.
  • the straw-like container can be made from any non-toxic moisture-resistant material such as plastic (e.g. polyethylene) or wax-coated paper.
  • the opening means on the straw-like container includes, for example, an end that is opened by tearing, or by removing a cap (via twisting or otherwise) . Once open, the contents of the container are simply emptied directly into the user's mouth.
  • the straw-like container used in this invention is intended to function like the straw-like container used in the PIXIE STICKTM children's granular candy dispenser.
  • non-straw-like container means any container that does not have a cylindrical shape whose length is greater than its width.
  • the dimensions of the non-straw-like container used in this invention can vary widely.
  • the non-straw- like container can be a "blister pack", which is -a widely used type of pharmaceutical container typically made from polymers such as polyvinyl chloride, polyvinylidine chloride (“PVDC”) and polychlorotrifluoroethylene (“Aclar ® ”) .
  • non-straw-like container can be oblong and non- cylindrically shaped, oblong and having only a portion which is cylindrically shaped, or cylindrically shaped wherein the width is greater than the length.
  • non-straw-like container can be a pouch, such as a foil/foil pouch, a foil/paper pouch, or a paper/paper pouch.
  • the opening means includes, for example, an end which is opened by tearing, or by removing a cap.
  • the instant dosage forms are packaged, along with a desiccant, within an outer, child-resistant container.
  • Child-resistant containers which meet the requirements of the Poison Prevention Packaging Act of 1970 (16 C.F.R. 1700, et seq.)
  • their methods of manufacture are standard in the art.
  • analgesics such as acetaminophen
  • An example of the latter "periodic” scenario is the use of antihistamines, such as brompheniramine, for relief of symptoms of seasonal allergies.
  • USP United States Pharmacopeia.
  • JP Japan Pharmacopeia.
  • JPE means Japan Pharmaceutical Excipient.
  • TYLENOL Acetaminophen

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Pain & Pain Management (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une composition pharmaceutique stable coulante sèche en granules conçue pour être administrée par voie orale et contenant des particules de médicaments ou de substances nutritives revêtus par un agent approprié masquant le goût, un agent provoquant la salivation et un véhicule acceptable sur le plan pharmaceutique. L'invention concerne également des formes galéniques pour une administration orale composées d'un récipient fermé résistant à l'humidité, soit sous forme de paille, soit sous une autre forme, possédant chacune une dose unitaire unique de la composition pharmaceutique et comportant des moyens d'ouverture permettant son administration orale sèche.
PCT/US1999/025454 1998-10-30 1999-10-28 Composition pharmaceutique coulante en granules et forme galenique sous forme de paille pour administration orale WO2000025744A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU12408/00A AU1240800A (en) 1998-10-30 1999-10-28 Granular, free-flowing pharmaceutical composition, and straw-like dosage form for oral administration thereof
JP2000579188A JP2002528483A (ja) 1998-10-30 1999-10-28 顆粒状で自由流動性の薬剤組成物、およびその経口投与のためのストロー状の投与形態
CA002348024A CA2348024C (fr) 1998-10-30 1999-10-28 Composition pharmaceutique coulante en granules et forme galenique sous forme de paille pour administration orale

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10630298P 1998-10-30 1998-10-30
US60/106,302 1998-10-30

Publications (1)

Publication Number Publication Date
WO2000025744A1 true WO2000025744A1 (fr) 2000-05-11

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PCT/US1999/025454 WO2000025744A1 (fr) 1998-10-30 1999-10-28 Composition pharmaceutique coulante en granules et forme galenique sous forme de paille pour administration orale

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JP (1) JP2002528483A (fr)
AU (1) AU1240800A (fr)
CA (1) CA2348024C (fr)
WO (1) WO2000025744A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102006007830A1 (de) * 2006-02-17 2007-08-30 Grünenthal GmbH Lagerstabile orale Darreichungsform von Amoxicillin und Clavulansäure
WO2007041367A3 (fr) * 2005-09-30 2007-11-29 Mcneil Ppc Inc Préparation orale contenant un agent induisant la salivation
US9919007B2 (en) 2013-03-15 2018-03-20 Braintree Laboratories, Inc. Dual use oral pharmaceutical composition tablets of sulfate salts and methods of use thereof
GR1010682B (el) * 2023-02-03 2024-04-29 Ιουλια Κλεωνος Τσετη Φαρμακευτικη συνθεση παρακεταμολης για αμεση καταποση χωρις νερο με βελτιωτικο γευσης συμβατο με την παρακεταμολη

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0317274A1 (fr) * 1987-11-16 1989-05-24 McNEIL-PPC, INC. Comprimé médicinal à mâcher contenant des moyens pour le masquage du goût
EP0383503A1 (fr) * 1989-02-17 1990-08-22 Eli Lilly And Company Dispositif pour administrer des médicaments par voie orale
WO1996007601A1 (fr) * 1994-09-07 1996-03-14 Ortho Pharmaceutical Corporation Emballage thermoforme a element de securite destine aux enfants et comportant un agent deshydratant
EP0717986A1 (fr) * 1994-12-19 1996-06-26 McNEIL-PPC, INC. Rotogranulation et enrobage d'acetaminophène, pseudoéphédrine, chlorphéniramine, et, eventuellement, dextrométhorphane
WO1997018798A1 (fr) * 1995-11-22 1997-05-29 Recordati S.A. Chemical And Pharmaceutical Company Compositions pharmaceutiques a liberation rapide
US5891476A (en) * 1997-12-22 1999-04-06 Reo; Joe P. Tastemasked pharmaceutical system

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0317274A1 (fr) * 1987-11-16 1989-05-24 McNEIL-PPC, INC. Comprimé médicinal à mâcher contenant des moyens pour le masquage du goût
EP0383503A1 (fr) * 1989-02-17 1990-08-22 Eli Lilly And Company Dispositif pour administrer des médicaments par voie orale
WO1996007601A1 (fr) * 1994-09-07 1996-03-14 Ortho Pharmaceutical Corporation Emballage thermoforme a element de securite destine aux enfants et comportant un agent deshydratant
EP0717986A1 (fr) * 1994-12-19 1996-06-26 McNEIL-PPC, INC. Rotogranulation et enrobage d'acetaminophène, pseudoéphédrine, chlorphéniramine, et, eventuellement, dextrométhorphane
WO1997018798A1 (fr) * 1995-11-22 1997-05-29 Recordati S.A. Chemical And Pharmaceutical Company Compositions pharmaceutiques a liberation rapide
US5891476A (en) * 1997-12-22 1999-04-06 Reo; Joe P. Tastemasked pharmaceutical system

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007041367A3 (fr) * 2005-09-30 2007-11-29 Mcneil Ppc Inc Préparation orale contenant un agent induisant la salivation
US8007825B2 (en) 2005-09-30 2011-08-30 Mcneil-Ppc, Inc. Oral compositions containing a salivation inducing agent
DE102006007830A1 (de) * 2006-02-17 2007-08-30 Grünenthal GmbH Lagerstabile orale Darreichungsform von Amoxicillin und Clavulansäure
US9919007B2 (en) 2013-03-15 2018-03-20 Braintree Laboratories, Inc. Dual use oral pharmaceutical composition tablets of sulfate salts and methods of use thereof
GR1010682B (el) * 2023-02-03 2024-04-29 Ιουλια Κλεωνος Τσετη Φαρμακευτικη συνθεση παρακεταμολης για αμεση καταποση χωρις νερο με βελτιωτικο γευσης συμβατο με την παρακεταμολη

Also Published As

Publication number Publication date
CA2348024C (fr) 2008-02-19
AU1240800A (en) 2000-05-22
CA2348024A1 (fr) 2000-05-11
JP2002528483A (ja) 2002-09-03

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