CA2348024C - Granular, free-flowing pharmaceutical composition, and straw-like dosage form for oral administration thereof - Google Patents
Granular, free-flowing pharmaceutical composition, and straw-like dosage form for oral administration thereof Download PDFInfo
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- CA2348024C CA2348024C CA002348024A CA2348024A CA2348024C CA 2348024 C CA2348024 C CA 2348024C CA 002348024 A CA002348024 A CA 002348024A CA 2348024 A CA2348024 A CA 2348024A CA 2348024 C CA2348024 C CA 2348024C
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- 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
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- 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
Abstract
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 dosage forms for oral administration comprising a closed, moisture-resistant container, either straw-like or non-straw-like, each 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 also provides dosage forms for oral administration comprising a closed, moisture-resistant container, either straw-like or non-straw-like, each having therein a single unit dose of the instant pharmaceutical composition, and having an opening means for permitting the dry oral administration thereof.
Description
GRANULAR, FREE-FLOWING PHARMACEUTICAL COMPOSITION, AND
STRAW-LIKE DOSAGE FORM FOR ORAL ADMINISTRATION THEREOF
Field of the Invention This invention relates to granular, free-flowing, pleasant tasting pharmaceutical compositions for or-al 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.
Background of the Invention 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 uripleasant 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. In some cases, 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.
A different approach is taken with a commercially available children's size tablet of acetaminophen, where the 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. This phenomenon is due to the fact that 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.
Despite the existing ability to mask unpleasant medicament taste in tablets and capsules, a need still exists for a more convenient way of administering these medicaments to those such as the very young and very old, who often have difficulty swallowing these types of -30 dosage forms. Even among the broader population, a great many people report difficulty in swallowing tablets and capsules.
For pediatric medicines, the use of liquid and chewable dosage forms predominates until children reach approximately 10-12 years of age. These dosages do not address all the needs of children in this age group. For example, problems with liquid dosage forms include uncertainty of delivered dose, limited stability after reconstitution (as seen with antibiotics), and poor .taste. As for older patients, many require medicine tablets to be crushed because of swallowing difficulties.
Indeed, the National Hospital Discharge Survey indicates that there is a 67% incidence of a discharge diagnosis of dysphagia among patients over age 65 (Department af Health and Human Services, National Center for Health Statistics (1989)). This incidence is almost five times higher than that seen among younger patients.
STRAW-LIKE DOSAGE FORM FOR ORAL ADMINISTRATION THEREOF
Field of the Invention This invention relates to granular, free-flowing, pleasant tasting pharmaceutical compositions for or-al 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.
Background of the Invention 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 uripleasant 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. In some cases, 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.
A different approach is taken with a commercially available children's size tablet of acetaminophen, where the 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. This phenomenon is due to the fact that 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.
Despite the existing ability to mask unpleasant medicament taste in tablets and capsules, a need still exists for a more convenient way of administering these medicaments to those such as the very young and very old, who often have difficulty swallowing these types of -30 dosage forms. Even among the broader population, a great many people report difficulty in swallowing tablets and capsules.
For pediatric medicines, the use of liquid and chewable dosage forms predominates until children reach approximately 10-12 years of age. These dosages do not address all the needs of children in this age group. For example, problems with liquid dosage forms include uncertainty of delivered dose, limited stability after reconstitution (as seen with antibiotics), and poor .taste. As for older patients, many require medicine tablets to be crushed because of swallowing difficulties.
Indeed, the National Hospital Discharge Survey indicates that there is a 67% incidence of a discharge diagnosis of dysphagia among patients over age 65 (Department af Health and Human Services, National Center for Health Statistics (1989)). This incidence is almost five times higher than that seen among younger patients.
Sumraary of the Invention 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 ther.eof.
Finally,,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.
=74'374-4 According to one aspect of the present invention, there is provided a dosage form for oral administration comprising: a closed, moisture resistant, straw-like container having therein a single unit dose of a pharmaceutical composition comprising a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable taste masking agent; particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
According to another aspect of the present invention, there is provided a dosage form for oral administration comprising: a closed, moisture resistant, non-straw-like container having therein a single unit dosage of a pharmaceutical composition consisting essentially of a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable polymeric taste masking agent;
particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid; and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
According to still another aspect of the present invention, there is provided a dosage form for oral administration comprising: a closed, moisture-resistant, non-straw-like container having therein a single unit dose 4a .74374-4 of a pharmaceutical composition consisting essentially of a dry, granular, free-flowing pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of a pharmaceutically effective amount of acetaminophen coated with a suitable polymeric taste-masking agent; particles of citric acid in an amount sufficient to permit dry oral administration without any intake of water or other liquid; particles of mannitol at a level of from about 30 to about 60% by weight, and particles of a sweetener, and having an opening means for permitting the dry oral administration thereof.
According to yet another aspect of the present invention, there is provided a dosage form for oral administration comprising a closed, moisture resistant container having a drinking straw shape and having therein a single unit dose of a pharmaceutical composition comprising a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising: a) particles of acetaminophen coated with a suitable taste masking agent; b) particles of an edible carboxylic acid selected from the group consisting of citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, adipic acid, and mixtures thereof in an amount sufficient to permit dry oral administration without any intake of water or other liquid; and c) particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof and wherein the pharmaceutical composition has a total water content of less than about 10% by weight.
4b Brief Description of the Figures 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 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 ther.eof.
Finally,,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.
=74'374-4 According to one aspect of the present invention, there is provided a dosage form for oral administration comprising: a closed, moisture resistant, straw-like container having therein a single unit dose of a pharmaceutical composition comprising a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable taste masking agent; particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
According to another aspect of the present invention, there is provided a dosage form for oral administration comprising: a closed, moisture resistant, non-straw-like container having therein a single unit dosage of a pharmaceutical composition consisting essentially of a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable polymeric taste masking agent;
particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid; and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
According to still another aspect of the present invention, there is provided a dosage form for oral administration comprising: a closed, moisture-resistant, non-straw-like container having therein a single unit dose 4a .74374-4 of a pharmaceutical composition consisting essentially of a dry, granular, free-flowing pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of a pharmaceutically effective amount of acetaminophen coated with a suitable polymeric taste-masking agent; particles of citric acid in an amount sufficient to permit dry oral administration without any intake of water or other liquid; particles of mannitol at a level of from about 30 to about 60% by weight, and particles of a sweetener, and having an opening means for permitting the dry oral administration thereof.
According to yet another aspect of the present invention, there is provided a dosage form for oral administration comprising a closed, moisture resistant container having a drinking straw shape and having therein a single unit dose of a pharmaceutical composition comprising a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising: a) particles of acetaminophen coated with a suitable taste masking agent; b) particles of an edible carboxylic acid selected from the group consisting of citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, adipic acid, and mixtures thereof in an amount sufficient to permit dry oral administration without any intake of water or other liquid; and c) particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof and wherein the pharmaceutical composition has a total water content of less than about 10% by weight.
4b Brief Description of the Figures 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.
Detailed Description of the Invention 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.
More specifically, 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.
In one embodiment, 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.
As used herein, the term "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 B6, B12, thiamin and folic acid.
Numerous analgesics are known in the art and 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. In the preferred embodiment, 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 mucolytic agents) useful in this invention include, for example, glyceryl guaiacolate, guaifenesin, terpin hydrate, ammonium chloride, N-acetylcysteine and -30 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.
especially tablets and capsules.
More specifically, 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.
In one embodiment, 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.
As used herein, the term "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 B6, B12, thiamin and folic acid.
Numerous analgesics are known in the art and 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. In the preferred embodiment, 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 mucolytic agents) useful in this invention include, for example, glyceryl guaiacolate, guaifenesin, terpin hydrate, ammonium chloride, N-acetylcysteine and -30 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, phenindamine, 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, temelastine, 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).
As used herein, the term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts deriv6d 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, hydrabamine, choline-, betaine, ethylenediamine,, glucosamine, methylglycamine, theobromine, purines, piperazine, piperidine, polyamine resins and the like.
All of these medicaments, as well as their acceptable dosage ranges, are described in U.S. Patent Nos. 4,783,465 and 4,619,934. Additional antitussives, expectorants, antihistamines, sympathomimetics, laxatives, antidiarrheals and analgesics suitable for use in the present invention'are described in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA, 18th ed., Chapters 39, 42, 43, 58 and 59 (1990)).
Methods of coating medicament and nutrient particles used in this invention with taste-masking agents are well known and commercially available in the pharmaceutical industry. Such methods are taught, for example, in U.S. Patent Nos. 5,489,436, 5,260,072, 5, 215, 755, 5, 489, 436, 5, 460, 825, and 4, 851, 224. These taste-masking agents include, for example, ethyl cellulose ("EC"); cellulose acetate ("CA"); cellulose -30 acetate butyrate ("CAB"); polymethacrylates such as dimethylaminoethyl methacrylate and neutral methacrylic acid ester (Eudragito E-100); hydroxypropyl cellulose ("HPC"); hydroxyethyl cellulose ("HEC"); and hydroxypropyl methyl cellulose ("HPMC").
Alternatively, medicament particles that are already taste-masked can be purchased commercially. For example, taste-masked acetaminophen particles are commercially available from Eurand America, Inc. (845 Center Drive, Vandalia, OH 45377), and taste-masked pseudoephedrine ("PE") and chiorpheniramine maleate ("CPM") particles are available from Particle Dynamics, Inc. (2503 South Hanley Road, St. Louis, MO 63144).
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.
One or more 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. In one embodiment, the salivation-inducing agent is an edible carboxylic acid such as citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, or adipic acid. Preferably, anhydrous carboxylic acids are used. The use of carboxylic acids in specific formulations is shown in the Examples section below.
In order to enhance its taste, mouth-feel and other physical properties, the instant pharmaceutical composition ideally includes components additional to the medicament, salivation-inducing agent, and carrier.
Thus, in one embodiment, the pharmaceutical composition further comprises one or more of a soothing agent, a sweetener, and a flavoring agent. In the-preferred embodiment, 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, 2nd ed. (American Pharmaceutical Association, Washington, D.C. (1994)).
In one embodiment, 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.
In another embodiment, the coated particles of the instant pharmaceutical composition comprise a plurality of medicaments and/or nutrients. Here, two possibilities exist, i.e., (i) 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.
In one example, 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 thereof.
'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. As used herein, "dry oral administration" means oral administration that does not require the concomitant intake of water or other liquid. In the preferred embodiment of the instant dosage forms, 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.
As used herein, 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. Finally, 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.
As used herein, the term "non-straw-like container" means any container that does not have a cylindrical shape whose length is greater than its width. As with the straw-like container, the dimensions of the non-straw-like container used in this invention can vary widely. For example, 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*"). Alternatively, the 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.
Moreover, non-straw-like container can be a pouch, such as a foil/foil pouch, a foil/paper pouch, or a paper/paper pouch. As with the straw-like container, the non-straw-like container can be made from any non-toxic moisture-resistant material such as plastic or wax-coated paper, and the opening means includes, for example, an end which is opened by tearing, or by removing a cap.
In one embodiment (and in the case of straw dosage forms the preferred embodiment), 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.)) and their methods of manufacture are standard in the art. Ideally, within each outer container is a plurality of individual dosage forms to be administered either on an "as needed" basis, or periodically over a prescribed length of time. An example of the former "as needed" scenario is the use of analgesics, such as acetaminophen, for pain relief. An example of the latter "periodic" scenario is the use of antihistamines, such as brompheniramine, for relief of symptoms of seasonal allergies.
This invention will be better understood by reference to the Examples that follow, but those skilled in the art will readily appreciate that they are only illustrative of the invention as described more fully in the claims which follow thereafter. In addition, various publications are cited throughout this application. The disclosure of these publications is hereby incorporated by reference into this application to describe more fully the state of the art to which this invention pertains.
Example 1 TYLENOL (Acetaminophen) Granules - I
Ingredient Unit Weight Weight Mg Percent Encapsulated Acetaminophen* 1075.3 59.74 Citric Acid USP (Anhydrous 20.0 1.11 Powder) Aspartame NF (Powder) 46.0 2.55 Alpine Cream Flavor Power 6.6 0.37 Natural and Artificial Lemon Juice Flavor 6.6 0.37 Mannitol (Granular) 645.5 35.86 Total 1800.0 100.00 *Equivalent to 1,000 mg of acetaminophen.
Physicals Actual Mesh Size % Retained Particle Size 20 0.1%
Analysis .30 2.0%
40 16.0%
60 62.9%
80 11.8%
100 2.5%
Pan 4.8%
Bulk Density 0.60g/mL
Tap Density 0.74 g/mL at 250 taps 0.74 g/mL at 500 taps Note: the following acronyms are used in the Examples.
"NF" means National Formulary.
"USP" means United States Pharmacopeia.
"JP" means Japan Pharmacopeia.
"JPE" means Japan Pharmaceutical Excipient.
Example 2 TYLENOL (Acetaminophen) Granules - I2 Ingredient Unit Weight Weight Mg Percent Encapsulated Acetaminophen* 1070.1 58.48 Fumaric Acid NF (Powder) 60.0 3.28 Aspartame NF (Powder) 46.0 2.51 Alpine Cream Flavor 6.6 0.36 Natural and Artificial 6.6 0.36 Lemon Juice Flavor Mannitol (Granular) 640.7 35.01 Total 1830.0 100.00 *Equivalent to 1,000 mg of acetaminophen.
Physicals Actual Mesh Size % Retained Particle Size Analysis 20 0.2%
30 1.8%
40 13.2%
60 63.4%
80 10.2%
100 7.0%
Pan 4.1%
Bulk Density 0.63g/mL
Tap Density 0.80g/mL at 50 taps Example 3 TYLENOL (Acetaminophen) Granules - III
Ingredient Unit Max. Daily Weight Weight Dose (mg) Percent (mg) ($) JP Mannitol 358.70 1076.10 51.24 JP Citric Acid Anhydrous 3.70 11.10 0.53 Lemon Juice Flavor 2.30 6.90 0.33 JP Magnesium Stearate 2.00 6.00 0.28 JP Acetaminophen 300.00 900.00 '42.86 JPE Ethylcellulose 33.30 99.90 4.76 Total Weight 700.00 2100.00 100.00 Physicals Actual Mesh Size % Retained Particle Size 20 0%
Analysis 35 1.8%
200 97.6%
Pan 0.6%
Example 4 Sore Throat Granules Ingredient Unit Weight Weight Percent Mg Encapsulated Acetaminophen* 571.4 56.95 Citric Acid USP (Anhydrous 7.0 0.7 Powder) Aspartame NF (Powder) 15.0 1.5 Prosweet Power 4.0 6.4 Artificial Cherry Flavor 2.5 0.25 Mixed Berry Flavor 1.0 0.1 Mannitol (Granular) 399.1 39.8 Dyclonine HC1 3.0 0.3 Total 1003.0 100.0 *Equivalent to 500 mg of acetaminophen.
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).
As used herein, the term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts deriv6d 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, hydrabamine, choline-, betaine, ethylenediamine,, glucosamine, methylglycamine, theobromine, purines, piperazine, piperidine, polyamine resins and the like.
All of these medicaments, as well as their acceptable dosage ranges, are described in U.S. Patent Nos. 4,783,465 and 4,619,934. Additional antitussives, expectorants, antihistamines, sympathomimetics, laxatives, antidiarrheals and analgesics suitable for use in the present invention'are described in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA, 18th ed., Chapters 39, 42, 43, 58 and 59 (1990)).
Methods of coating medicament and nutrient particles used in this invention with taste-masking agents are well known and commercially available in the pharmaceutical industry. Such methods are taught, for example, in U.S. Patent Nos. 5,489,436, 5,260,072, 5, 215, 755, 5, 489, 436, 5, 460, 825, and 4, 851, 224. These taste-masking agents include, for example, ethyl cellulose ("EC"); cellulose acetate ("CA"); cellulose -30 acetate butyrate ("CAB"); polymethacrylates such as dimethylaminoethyl methacrylate and neutral methacrylic acid ester (Eudragito E-100); hydroxypropyl cellulose ("HPC"); hydroxyethyl cellulose ("HEC"); and hydroxypropyl methyl cellulose ("HPMC").
Alternatively, medicament particles that are already taste-masked can be purchased commercially. For example, taste-masked acetaminophen particles are commercially available from Eurand America, Inc. (845 Center Drive, Vandalia, OH 45377), and taste-masked pseudoephedrine ("PE") and chiorpheniramine maleate ("CPM") particles are available from Particle Dynamics, Inc. (2503 South Hanley Road, St. Louis, MO 63144).
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.
One or more 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. In one embodiment, the salivation-inducing agent is an edible carboxylic acid such as citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, or adipic acid. Preferably, anhydrous carboxylic acids are used. The use of carboxylic acids in specific formulations is shown in the Examples section below.
In order to enhance its taste, mouth-feel and other physical properties, the instant pharmaceutical composition ideally includes components additional to the medicament, salivation-inducing agent, and carrier.
Thus, in one embodiment, the pharmaceutical composition further comprises one or more of a soothing agent, a sweetener, and a flavoring agent. In the-preferred embodiment, 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, 2nd ed. (American Pharmaceutical Association, Washington, D.C. (1994)).
In one embodiment, 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.
In another embodiment, the coated particles of the instant pharmaceutical composition comprise a plurality of medicaments and/or nutrients. Here, two possibilities exist, i.e., (i) 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.
In one example, 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 thereof.
'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. As used herein, "dry oral administration" means oral administration that does not require the concomitant intake of water or other liquid. In the preferred embodiment of the instant dosage forms, 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.
As used herein, 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. Finally, 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.
As used herein, the term "non-straw-like container" means any container that does not have a cylindrical shape whose length is greater than its width. As with the straw-like container, the dimensions of the non-straw-like container used in this invention can vary widely. For example, 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*"). Alternatively, the 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.
Moreover, non-straw-like container can be a pouch, such as a foil/foil pouch, a foil/paper pouch, or a paper/paper pouch. As with the straw-like container, the non-straw-like container can be made from any non-toxic moisture-resistant material such as plastic or wax-coated paper, and the opening means includes, for example, an end which is opened by tearing, or by removing a cap.
In one embodiment (and in the case of straw dosage forms the preferred embodiment), 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.)) and their methods of manufacture are standard in the art. Ideally, within each outer container is a plurality of individual dosage forms to be administered either on an "as needed" basis, or periodically over a prescribed length of time. An example of the former "as needed" scenario is the use of analgesics, such as acetaminophen, for pain relief. An example of the latter "periodic" scenario is the use of antihistamines, such as brompheniramine, for relief of symptoms of seasonal allergies.
This invention will be better understood by reference to the Examples that follow, but those skilled in the art will readily appreciate that they are only illustrative of the invention as described more fully in the claims which follow thereafter. In addition, various publications are cited throughout this application. The disclosure of these publications is hereby incorporated by reference into this application to describe more fully the state of the art to which this invention pertains.
Example 1 TYLENOL (Acetaminophen) Granules - I
Ingredient Unit Weight Weight Mg Percent Encapsulated Acetaminophen* 1075.3 59.74 Citric Acid USP (Anhydrous 20.0 1.11 Powder) Aspartame NF (Powder) 46.0 2.55 Alpine Cream Flavor Power 6.6 0.37 Natural and Artificial Lemon Juice Flavor 6.6 0.37 Mannitol (Granular) 645.5 35.86 Total 1800.0 100.00 *Equivalent to 1,000 mg of acetaminophen.
Physicals Actual Mesh Size % Retained Particle Size 20 0.1%
Analysis .30 2.0%
40 16.0%
60 62.9%
80 11.8%
100 2.5%
Pan 4.8%
Bulk Density 0.60g/mL
Tap Density 0.74 g/mL at 250 taps 0.74 g/mL at 500 taps Note: the following acronyms are used in the Examples.
"NF" means National Formulary.
"USP" means United States Pharmacopeia.
"JP" means Japan Pharmacopeia.
"JPE" means Japan Pharmaceutical Excipient.
Example 2 TYLENOL (Acetaminophen) Granules - I2 Ingredient Unit Weight Weight Mg Percent Encapsulated Acetaminophen* 1070.1 58.48 Fumaric Acid NF (Powder) 60.0 3.28 Aspartame NF (Powder) 46.0 2.51 Alpine Cream Flavor 6.6 0.36 Natural and Artificial 6.6 0.36 Lemon Juice Flavor Mannitol (Granular) 640.7 35.01 Total 1830.0 100.00 *Equivalent to 1,000 mg of acetaminophen.
Physicals Actual Mesh Size % Retained Particle Size Analysis 20 0.2%
30 1.8%
40 13.2%
60 63.4%
80 10.2%
100 7.0%
Pan 4.1%
Bulk Density 0.63g/mL
Tap Density 0.80g/mL at 50 taps Example 3 TYLENOL (Acetaminophen) Granules - III
Ingredient Unit Max. Daily Weight Weight Dose (mg) Percent (mg) ($) JP Mannitol 358.70 1076.10 51.24 JP Citric Acid Anhydrous 3.70 11.10 0.53 Lemon Juice Flavor 2.30 6.90 0.33 JP Magnesium Stearate 2.00 6.00 0.28 JP Acetaminophen 300.00 900.00 '42.86 JPE Ethylcellulose 33.30 99.90 4.76 Total Weight 700.00 2100.00 100.00 Physicals Actual Mesh Size % Retained Particle Size 20 0%
Analysis 35 1.8%
200 97.6%
Pan 0.6%
Example 4 Sore Throat Granules Ingredient Unit Weight Weight Percent Mg Encapsulated Acetaminophen* 571.4 56.95 Citric Acid USP (Anhydrous 7.0 0.7 Powder) Aspartame NF (Powder) 15.0 1.5 Prosweet Power 4.0 6.4 Artificial Cherry Flavor 2.5 0.25 Mixed Berry Flavor 1.0 0.1 Mannitol (Granular) 399.1 39.8 Dyclonine HC1 3.0 0.3 Total 1003.0 100.0 *Equivalent to 500 mg of acetaminophen.
Claims (33)
1. A dosage form for oral administration comprising:
a closed, moisture resistant, straw-like container having therein a single unit dose of a pharmaceutical composition comprising a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable taste masking agent; particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid; and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
a closed, moisture resistant, straw-like container having therein a single unit dose of a pharmaceutical composition comprising a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable taste masking agent; particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid; and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
2. The dosage form of claim 1, wherein the medicament is acetaminophen.
3. The dosage form of claim 1 or 2, wherein the form is packaged, along with a desiccant, within an outer, child-resistant container.
4. The dosage form of any one of claims 1 to 3, wherein the salivation-inducing agent is an edible carboxylic acid.
5. The dosage form of any one of claims 1 to 3, wherein the salivation-inducing agent is selected from the group consisting of citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, adipic acid, and mixtures thereof.
6. The dosage form of any one of claims 1 to 5, further comprising a soothing agent and a sweetener.
7. The dosage form of claim 6, wherein the soothing agent exhibits a negative heat of hydration.
8. The dosage form of claim 7, wherein the soothing agent is selected from the group consisting of mannitol, sorbitol, and xylitol.
9. The dosage form of claim 6, wherein said sweetener is selected from the group consisting of aspartame, sucralose, saccharine, cyclamate, acesulfame potassium, mannitol, sorbitol, and xylitol.
10. The dosage form of any one of claims 1 to 9, wherein the pharmaceutical composition has a total water content of less than about 10% by weight.
11. A dosage form for oral administration comprising:
a closed, moisture resistant, non-straw-like container having therein a single unit dosage of a pharmaceutical composition consisting essentially of a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable polymeric taste masking agent; particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
a closed, moisture resistant, non-straw-like container having therein a single unit dosage of a pharmaceutical composition consisting essentially of a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of medicament or nutrient coated with a suitable polymeric taste masking agent; particles of a salivation inducing agent in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
and particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof.
12. The dosage form of claim 11, wherein the medicament is acetaminophen.
13. The dosage form of claim 11 or 12, wherein said container is a pouch.
14. The dosage form of any one of claims 11 to 13, wherein said pharmaceutical composition remains physically and chemically stable in said container for at least about two years.
15. The dosage form of any one of claims 11 to 14, wherein the form is packaged, along with a desiccant, within an outer, child-resistant container.
16. The dosage form of any one of claims 11 to 15, wherein the salivation-inducing agent is an edible carboxylic acid.
17. The dosage form of any one of claims 11 to 15, wherein the salivation-inducing agent is selected from the group consisting of citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, adipic acid, and mixtures thereof.
18. The dosage form of any one of claims 11 to 17, further comprising a soothing agent and a sweetener.
19. The dosage form of claim 18, wherein the soothing agent exhibits a negative heat of hydration.
20. The dosage form of claim 19, wherein the soothing agent is selected from the group consisting of mannitol, sorbitol, and xylitol.
21. The dosage form of claim 18, wherein said sweetener is selected from the group consisting of aspartame, sucralose, saccharine, cyclamate, acesulfame potassium, mannitol, sorbitol, and xylitol.
22. The dosage form of any one of claims 11 to 21, wherein the pharmaceutical composition has a total water content of less than 10% by weight.
23. A dosage form for oral administration comprising:
a closed, moisture-resistant, non-straw-like container having therein a single unit dose of a pharmaceutical composition consisting essentially of a dry, granular, free-flowing pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of a pharmaceutically effective amount of acetaminophen coated with a suitable polymeric taste-masking agent; particles of citric acid in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
particles of mannitol at a level of from about 30 to about 60% by weight, and particles of a sweetener, and having an opening means for permitting the dry oral administration thereof.
a closed, moisture-resistant, non-straw-like container having therein a single unit dose of a pharmaceutical composition consisting essentially of a dry, granular, free-flowing pharmaceutical composition for oral administration, said pharmaceutical composition comprising particles of a pharmaceutically effective amount of acetaminophen coated with a suitable polymeric taste-masking agent; particles of citric acid in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
particles of mannitol at a level of from about 30 to about 60% by weight, and particles of a sweetener, and having an opening means for permitting the dry oral administration thereof.
24. The dosage form of claim 23, wherein the pharmaceutical composition has a total water content of less than about 10% by weight.
25. The dosage form of claim 23 or 24, wherein said container is a pouch.
26. The dosage form of any one of claims 23 to 25, wherein said pharmaceutical composition remains physically and chemically stable in said container for at least about two years.
27. A dosage form for oral administration comprising a closed, moisture resistant container having a drinking straw shape and having therein a single unit dose of a pharmaceutical composition comprising a dry, granular, free flowing stable pharmaceutical composition for oral administration, said pharmaceutical composition comprising:
a) particles of acetaminophen coated with a suitable taste masking agent;
b) particles of an edible carboxylic acid selected from the group consisting of citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, adipic acid, and mixtures thereof in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
and c) particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof and wherein the pharmaceutical composition has a total water content of less than about 10% by weight.
a) particles of acetaminophen coated with a suitable taste masking agent;
b) particles of an edible carboxylic acid selected from the group consisting of citric acid, malic acid, fumaric acid, benzoic acid, sorbic acid, adipic acid, and mixtures thereof in an amount sufficient to permit dry oral administration without any intake of water or other liquid;
and c) particles of a pharmaceutically acceptable carrier, said container having an opening means for permitting the dry oral administration thereof and wherein the pharmaceutical composition has a total water content of less than about 10% by weight.
28. The dosage form of claim 27, wherein the form is packaged, along with a desiccant, within an outer, child-resistant container.
29. The dosage form of claim 27 or 28, further comprising a soothing agent and a sweetener.
30. The dosage form of claim 29, wherein the soothing agent exhibits a negative heat of hydration.
31. The dosage form of claim 30, wherein the soothing agent is selected from the group consisting of mannitol, sorbitol, and xylitol.
32. The dosage form of claim 31, wherein said sweetener is selected form the group consisting of aspartame, sucralose, saccharine, cyclamate, acesulfame potassium, mannitol, sorbitol, and xylitol.
33. The dosage form of any one of claims 27 to 32, wherein said pharmaceutical composition remains physically and chemically stable in said container for at least about two years.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10630298P | 1998-10-30 | 1998-10-30 | |
| US60/106,302 | 1998-10-30 | ||
| PCT/US1999/025454 WO2000025744A1 (en) | 1998-10-30 | 1999-10-28 | Granular, free-flowing pharmaceutical composition, and straw-like dosage form for oral administration thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2348024A1 CA2348024A1 (en) | 2000-05-11 |
| CA2348024C true CA2348024C (en) | 2008-02-19 |
Family
ID=22310679
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002348024A Expired - Fee Related CA2348024C (en) | 1998-10-30 | 1999-10-28 | Granular, free-flowing pharmaceutical composition, and straw-like dosage form for oral administration thereof |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2002528483A (en) |
| AU (1) | AU1240800A (en) |
| CA (1) | CA2348024C (en) |
| WO (1) | WO2000025744A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070077300A1 (en) | 2005-09-30 | 2007-04-05 | Wynn David W | Oral compositions containing a salivation inducing agent |
| DE102006007830A1 (en) * | 2006-02-17 | 2007-08-30 | Grünenthal GmbH | Storage-stable oral dosage form of amoxicillin and clavulanic acid |
| ME03656B (en) | 2013-03-15 | 2020-07-20 | Braintree Laboratories Inc | Dual use oral pharmaceutical composition tablets of sulfate saltes and methods of use thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ226822A (en) * | 1987-11-16 | 1990-03-27 | Mcneil Consumer Prod | Chewable medicament tablet containing means for taste masking |
| US4981468A (en) * | 1989-02-17 | 1991-01-01 | Eli Lilly And Company | Delivery device for orally administered therapeutic agents |
| CH687615A5 (en) * | 1994-09-07 | 1997-01-15 | R W Johnson Pharmaceutical Res | Tropical packaging. |
| US5529783A (en) * | 1994-12-19 | 1996-06-25 | Mcneil-Ppc, Inc. | Rotor granulation and coating of acetaminophen, pseudoephedrine, chlorpheniramine, and, optionally dextromethorphan |
| IT1276160B1 (en) * | 1995-11-22 | 1997-10-27 | Recordati Chem Pharm | READY-RELEASE ORAL PHARMACEUTICAL COMPOSITIONS FOR EXTEMPORARY SUSPENSIONS |
| US5891476A (en) * | 1997-12-22 | 1999-04-06 | Reo; Joe P. | Tastemasked pharmaceutical system |
-
1999
- 1999-10-28 AU AU12408/00A patent/AU1240800A/en not_active Abandoned
- 1999-10-28 WO PCT/US1999/025454 patent/WO2000025744A1/en active Application Filing
- 1999-10-28 CA CA002348024A patent/CA2348024C/en not_active Expired - Fee Related
- 1999-10-28 JP JP2000579188A patent/JP2002528483A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000025744A1 (en) | 2000-05-11 |
| AU1240800A (en) | 2000-05-22 |
| JP2002528483A (en) | 2002-09-03 |
| CA2348024A1 (en) | 2000-05-11 |
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