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
  • A61K31/13—Amines
  • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
  • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• • 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
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
  • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
  • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/365—Lactones
  • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/47—Quinolines; Isoquinolines
  • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
  • A61K31/52—Purines, e.g. adenine
  • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
  • A61K36/258—Panax (ginseng)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2013—Organic compounds, e.g. phospholipids, fats
  • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
  • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
  • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
  • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer

Definitions

• the invention relates to the field of tablets for oral delivery of active ingredients.
• the tablets of the invention are suitable for high load delivery of active ingredients.
• a high load of active ingredients may cause issues for the overall sensorial properties of the tablets. Both the nature of the active ingredients with respect to taste properties and pronounced bitterness for some active ingredients, and the high amount of actives relative to other ingredients in the tablets, may be a challenge to formulation specialists.
• One of the more critical issues is that it is often difficult to formulate tablets for oral delivery with suitable sensorial properties, particularly when the active ingredient is present in a high load.
• Sensorial properties in the present context include the overall mouthfeel of the tablet when chewed and the resulting delivery of the active ingredients in the oral cavity. For instance, a pronounced powdery sense is often not convenient to the user and as a result may often provide inferior tablets that are not used on a frequent basis.
• a formulation is to be provided that may also help in obtaining improved sensorics properties.
• important sensorics properties include friability, texture, flavor perception, sweetness perception and off-notes associated with the actives. These properties are both relevant from a convenience perspective in chewable tablets, but certainly also in order to support an appropriate delivery of actives from the tablets and avoid adverse side effects of the actives.
• an oral chewable tablet suitable for improved mouthfeel comprising dextrose in an amount from 50 to 95% by weight of the tablet; one or more active ingredients; and one or more binders, wherein the ratio between the one or more binders and dextrose is from 1 :250 to 1 :8.
• Providing a chewable tablet according to the invention may solve various problems of the prior art and aims at establishing a chewable tablet that combines beneficial delivery properties of actives combined with advantageous sensorial properties.
• the crux of the oral chewable tablets according to the invention is the combination of a relatively high amount of dextrose combined with one or more binders that are applied as separate elements in the formulation and one or more active ingredients.
• the “one or more binders” are to be understood as binders that are added separately in the formulation and not being part or integrated in other ingredients in the formulation.
• One advantage of the invention is a surprisingly strong saliva generation compared to conventional chewable tablets and lozenges. Increased generation of saliva may have a huge impact on the delivery of the one or more active ingredients. Specifically, when increased generation of saliva is coordinated with release of the one or more active ingredients from the tablet, relatively quick delivery is obtained. Hence, a synergy between the effect of the one or more active ingredients and increased saliva generation may be seen according to the invention.
• One unexpected advantage over the prior art is that the saliva generation is surprisingly sustained even after a user has swallowed the bulk-portion of the dextrose. This sustaining of the salivation generation may be advantageous in relation to many applications of a chewable tablet ranging from mouthfeel, taste, flavor perception, etc.
• a very important aspect of the present invention is the provision of beneficial sensorial properties.
• important sensorial properties include mouthfeel, ease of chewing/melting into liquid, friability (mechanical robustness), texture, flavor perception, sweetness perception and off-notes associated with the one or more active ingredients. These properties are both relevant from a convenience perspective in chewable tablets, but certainly also in order to support an appropriate delivery of the one or more active ingredients from the chewable tablet formulation, such as an improved release profile, and to avoid adverse side effects of the one or more active ingredients.
• the present inventor has shown very surprising results with the specific combination of features of the present invention in terms of these sensorial properties. It was an unexpected result that the invention could both contribute to an improved release profile, such as rapid release of the one or more active ingredients, and at the same time provide very beneficial sensorics properties which in terms may also support an appropriate delivery of the one or more active ingredients from the chewable tablet.
• friability of the oral tablet Both in order to secure a desired release of the one or more active ingredients and to improve the sensation by a consumer, it is critical that friability is balanced. Also, the mouthfeel of the oral tablet during use is critical for the release of the one or more active ingredients and the experience as well as convenience during use. These properties may be improved by the present invention which was not expected by the inventor of the present invention.
• a “chewable tablet” is intended to mean an oral tablet that is chewed upon oral administration, having characteristics allowing convenient chewing without adverse side effects associated with the texture of the oral tablet.
• a content of about 1% of one or more binders in the chewable tablets according to the invention such as a range about 0.5 to 3% of one or more binders in the chewable tablet according to the invention.
• this amount as well as the range may provide superior results for tablets with a content of 50 to 95% by weight of dextrose.
• this amount may be beneficial both for tablets with a high of active ingredients, such as 30% load, or low load of active ingredients, such as 1 mg. While this amount is preferred, however, as will appear from further embodiments of the invention, other amounts or ranges may be applied with suitable results.
• the ratio between the one or more binders and dextrose is from 1 :250 to 1 :25 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet.
• the term “if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet” or similar wordings is intended to be understood as a proviso that under the circumstances where the content of dextrose is in the range of 70 to 95% by weight of the tablet, then the ratio between the one or more binders and dextrose is from 1 :250 to 1 :25.
• This proviso is to be understood in context of the broader ratio between the one or more binders and dextrose and the broader range of the presence of dextrose, i.e., the proviso is a sub-division of the broader ratios and ranges.
• the proviso illustrates this dynamic in the present invention for some embodiments.
• the ratio between the one or more binders and dextrose is from 1 :250 to 1 :50 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet.
• the ratio between the one or more binders and dextrose is higher than 1 :250 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet. In some further embodiments of the invention, the ratio between the one or more binders and dextrose is higher than 1 :200 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet. In some further embodiments of the invention, the ratio between the one or more binders and dextrose is higher than 1 : 150 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet.
• the ratio between the one or more binders and dextrose is higher than 1 : 125 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet. In some further embodiments of the invention, the ratio between the one or more binders and dextrose is higher than 1 : 100 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet.
• the ratio between the one or more binders and dextrose is lower than 1 :25 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet. In some further embodiments of the invention, the ratio between the one or more binders and dextrose is lower than 1 :50 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet. In some further embodiments of the invention, the ratio between the one or more binders and the dextrose is lower than 1 :75 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet.
• the ratio between the one or more binders and dextrose is from 1 :200 to 1 :50 if the tablet comprises dextrose in an amount from 70 to 95% by weight of the tablet.
• the term “if the tablet comprises dextrose in an amount from 50 to 70% by weight of the tablet” or similar wordings is intended to be understood as a proviso that under the circumstances where the content of dextrose is in the range of 50 to 70% by weight of the tablet, then the ratio between the one or more binders and dextrose is from 1 : 100 to 1 :8.
• This proviso is to be understood in context of the broader ratio between the one or more binders and dextrose and the broader range of the presence of dextrose, i.e., the proviso is a sub-division of the broader ratios and ranges.
• the ratio between the one or more binders and dextrose is from 1 : 100 to 1 : 10 if the tablet comprises dextrose in an amount from 50 to 70% by weight of the tablet.
• the ratio between the one or more binders and dextrose is from 1 :75 to 1 : 15 if the tablet comprises dextrose in an amount from 50 to 70% by weight of the tablet.
• the ratio between the one or more binders and dextrose is lower than 1 :8 if the tablet comprises dextrose in an amount from 50 to 70% by weight of the tablet. In some further embodiments of the invention, the ratio between the one or more binders and dextrose is lower than 1 : 10 if the tablet comprises dextrose in an amount from 50 to 70% by weight of the tablet. In some further embodiments of the invention, the ratio between the one or more binders and dextrose is lower than 1 :20 if the tablet comprises dextrose in an amount from 50 to 70% by weight of the tablet.
• the ratio between the one or more binders and the one or more active ingredients is from 1 : 50 to 1 : 10.
• the ratio between the one or more binders and the one or more active ingredients is from 1 :30 to 1 : 15.
• the ratio between the one or more binders and the one or more active ingredients may be from 8: 1 to 1 :8. In some embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients may be from 6: 1 to 1 :6. In some embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients may be from 4: 1 to 1 :4. In some embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients may be from 2: 1 to 1 :2.
• the ratio between the one or more binders and the one or more active ingredients is lower than 1 :25. In some further embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients is lower than 1 :50. In some further embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients is lower than 1 :75.
• the ratio between the one or more binders and the one or more active ingredients is lower than 1 :8. In some further embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients is lower than 1 : 10. In some further embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients is lower than 1 :20. In some further embodiments of the invention, the ratio between the one or more binders and the one or more active ingredients is lower than 1 : 15.
• dextrose is present in an amount from 55 to 95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount from 60 to 95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount from 65 to 95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount from 70 to 95% by weight of the tablet. In some embodiments of the invention, dextrose is present in an amount from 70 to 90% by weight of the tablet.
• the oral chewable tablet is consisting essentially of dextrose, one or more active ingredients and one or more binders, except for auxiliary ingredients present up to about 5% by weight of the tablet.
• Flavors, high intensity sweeteners and glidant are examples of auxiliary ingredients that may be added in low amounts according to the invention without compromising the platform consisting of dextrose, the one or more binders and the one or more active ingredients according to the invention.
• auxiliary ingredients that may be added in low amounts according to the invention without compromising the platform consisting of dextrose, the one or more binders and the one or more active ingredients according to the invention.
• a major part of the chewable tablets is composed of dextrose, the one or more binders and the one or more active ingredients according to the invention.
• the overall system of the chewable tablet is controlled by these ingredients, including the special improved sensorial benefits of the invention, such as an improved mouth-feel, as well as saliva generation, and as well as friability properties.
• the oral chewable tablet is consisting essentially of dextrose, one or more active ingredients and one or more binders.
• the oral chewable tablet does not comprise sugar alcohol. It is contemplated that sugar alcohols in some embodiments are detrimental to the platform properties according to the invention, including sensorial properties, such as mouth-feel. In some embodiments, however, low amounts of sugar alcohol may be added, such as low amount of mannitol, such as less than 5% by weight.
• the oral chewable tablet does not comprise gum base.
• the presence of gum base may impact the sensorial properties of the tablet as well as release of active ingredients.
• the dextrose comprises anhydrous dextrose. In some embodiments of the invention, the dextrose comprises hydrated dextrose. In some embodiments of the invention, the dextrose comprises dextrose monohydrate. In some embodiments of the invention, the dextrose comprises at least 90% dextrose equivalents calculated on a dry basis. In some embodiments of the invention, the dextrose comprises at least 93% dextrose equivalents calculated on a dry basis. In some embodiments of the invention, the dextrose comprises at least 95% dextrose equivalents calculated on a dry basis. In some embodiments of the invention, the dextrose comprises at least 98% dextrose equivalents calculated on a dry basis.
• the dextrose is directly compressible (DC).
• the dextrose comprises at least 80% by weight of particles below 500 microns.
• the dextrose comprises at most 10% by weight of particles above 500 microns.
• the dextrose comprises at most 35% by weight of particles below 100 microns.
• the dextrose comprises at least 30% by weight of particles in the range of 180 to 500 microns.
• the dextrose comprises at least 50% by weight of particles in the range of 180 to 500 microns.
• the dextrose comprises at least 30% by weight of particles in the range of 250 to 500 microns.
• the dextrose comprises at least 50% by weight of particles above 250 microns.
• the dextrose comprises at least 10% by weight of particles above 500 microns. In some embodiments of the invention, the dextrose comprises at most 35% by weight of particles below 100 microns. In some embodiments of the invention, the dextrose comprises at most 10% by weight of particles above 500 microns.
• One presently preferred grade of dextrose comprises C*DexTM 02001 provided by Cargill.
• Another grade of dextrose comprises Cerelose® dextrose 020010 provided by Ingredion.
• the dextrose comprises at most 25% by weight of particles below 149 microns. In some embodiments of the invention, the dextrose comprises at most 35% by weight of particles below 177 microns.
• One grade of dextrose comprises Royal-T® provided by Ingredion.
• the one or more binders is present in an amount of 0.4 to 5% by weight of the tablet.
• the one or more binders is present in an amount of 0.7 to 3% by weight of the tablet.
• the one or more binders is present in an amount of 0.7 to 2% by weight of the tablet.
• the one or more binders is present in an amount of 0.7 to 1.3% by weight of the tablet. In some embodiments of the invention, the one or more binders is present in an amount of 2 to 15% by weight of the tablet.
• the one or more binders is present in an amount of 3 to 10% by weight of the tablet.
• the one or more binders is present in an amount of 4 to 6% by weight of the tablet. In some embodiments of the invention, the one or more binders is present in an amount of 2 to 7% by weight of the tablet. In some embodiments of the invention, the one or more binders is present in an amount of 2 to 5% by weight of the tablet. In some embodiments of the invention, the one or more binders is present in an amount of 3 to 7% by weight of the tablet. In some embodiments of the invention, the one or more binders is present in an amount of 3 to 6% by weight of the tablet. In some embodiments of the invention, the one or more binders is present in an amount of 3 to 5% by weight of the tablet.
• the one or more binders is added separately in the formulation and being separate from any binder being integrated in other ingredients in the tablet.
• HPMC may be applied as a particular attractive binder.
• this binder when used with dextrose, exhibits an advantageous sensory experience when compared to other well-known binders.
• the use of HPMC lower than 4 % by weight of the tablet is advantageous, such as 0.1 to 3%, such as 0.1 to 2% by weight of the tablet.
• the one or more active ingredients is present in an amount of 5 to 30% by weight of the tablet.
• the one or more active ingredients is present in an amount of 10 to 30% by weight of the tablet.
• the one or more active ingredients comprise a non-directly compressible (non-DC) active ingredient in an amount of 5 to 50% by weight of the tablet.
• the one or more active ingredients comprise a non-directly compressible (non-DC) active ingredient in an amount of 20 to 50% by weight of the tablet. In some embodiments of the invention, the one or more active ingredients comprise a non-directly compressible (non-DC) active ingredient in an amount of 30 to 50% by weight of the tablet.
• the one or more active ingredients comprise a directly compressible (DC) active ingredient.
• DC directly compressible
• the one or more active ingredients comprise an immune supporting active ingredient.
• the one or more active ingredients comprise a mixture of immune supporting active ingredients.
• the one or more active ingredients comprise an energy stimulating active ingredient
• the one or more active ingredients comprise a mixture of vitamins, minerals, and herbals.
• the one or more active ingredients comprise Vitamin C. In some embodiments of the invention, the one or more active ingredients comprise melatonin. In some embodiments of the invention, the one or more active ingredients comprise theanine. In some embodiments of the invention, the one or more active ingredients comprise calcium carbonate. In some embodiments of the invention, the one or more active ingredients comprise caffeine.
• the one or more active ingredients comprise multivitamin. In some embodiments of the invention, the one or more active ingredients comprise Zn-oxide. In some embodiments of the invention, the one or more active ingredients comprise Zn-citrate. In some embodiments of the invention, the one or more active ingredients comprise Zn-gluconate. In some embodiments of the invention, the one or more active ingredients comprise Vitamin D.
• the one or more active ingredients comprise acetaminophen. In some embodiments of the invention, the one or more active ingredients comprise phenylephrine. In some embodiments of the invention, the one or more active ingredients comprise dextromethorphan. In some embodiments of the invention, the one or more active ingredients comprise guaifenesin. In some embodiments of the invention, the one or more active ingredients comprise a combination of acetaminophen, phenylephrine, dextromethorphan, and guaifenesin.
• the active ingredient is selected from acetylcysteine, ambroxol, amylmetacresol, benzocaine, bisacodyl, bismuth subsalicylate, bromhexine, cetirizine, , dextromethorphan hydrobromide, 2,4- di chlorobenzyl alcohol, doxylamine succinate, , flurbiprofen, glycerin, hexylresorcinol, lidocaine, menthol, myrrh, paracetamol, pectin, peppermint oil, phenol, phenylephrine hydrochloride, povidone-iodine, pseudoephedrine, ranitidine, simethicone, sodium docusate, spearmint, zinc, or any combination thereof.
• active ingredients are active ingredients that may be delivered to the throat.
• the tablet may comprise further active ingredient, e.g. a combination of two or more active ingredients from the above list, or as a combination of an active ingredient from the above list and another active ingredient.
• the active ingredient is an analgesic.
• analgesics include e.g. ibuprofen, paracetamol (acetaminophen), ketoprofen, aspirin (acetylsalicylic acid), and naproxen.
• the active ingredient is an anesthetic.
• the active ingredient is an anti-inflammation agent.
• the active ingredient is a disinfectant.
• the active ingredient is a cough suppressant.
• cough suppressants include e.g. dextromethorphan.
• the active ingredient is an expectorant, such as guaifenesin.
• the active ingredient is a local anesthetic.
• local anesthetics include e.g. ambroxol, benzocaine and hexylresorcinol.
• the active ingredient is a member of the morphinan class.
• members of the morphinan class include e.g. dextromethorphan.
• the active ingredient is a non-steroidal antiinflammatory drug (NSAID).
• NSAIDs non-steroidal anti-inflammatory drugs
• flurbiprofen examples include e.g. flurbiprofen.
• the active ingredient is an anti-inflammation agent. In an embodiment of the invention the active ingredient is a disinfectant.
• the active ingredient is a cough and cold agent.
• the tablet comprises cough and cold agents including acetaminophen, dextromethorphan hydrobromide, guaifenesin and phenylephrine hydrochloride.
• the tablet comprises cough and cold agents including acetaminophen, dextromethorphan hydrobromide and phenylephrine hydrochloride.
• the active ingredient is an enzyme.
• One advantage of enzymes may be that digestion may be accelerated and/or that intestinal balance is restored or improved.
• the active ingredient is an opioid.
• the tablet is a medical device for alleviating or treating dysphagia by inducing saliva generation.
• the active ingredient is cetirizine. In an embodiment of the invention the active ingredient is bromhexine. In an embodiment of the invention the active ingredient is amylmetacresol. In an embodiment of the invention the active ingredient is paracetamol. In an embodiment of the invention active ingredient is acetaminophen. In an embodiment of the invention the active ingredient is dextromethorphan HBr. In an embodiment of the invention the active ingredient is guaifenesin. In an embodiment of the invention the active ingredient is phenylephrine HC1. In an embodiment of the invention the active ingredient is penicillin.
• the tablet further comprising a plant extract, such as red clover or willow extract.
• the tablet further comprising a plant extract, such as Echinacea, Camille or Lavender.
• the plat extract is combined in the tablet with zinc gluconate and ascorbic acid.
• the oral tablet is essentially consisting of ingredients that are present in nature.
• the may comprise further active ingredient, e.g. a combination of two or more active ingredients from the above list, or as a combination of an active ingredient from the above list and another active ingredient.
• the active ingredient is an analgesic.
• analgesics include e.g. ibuprofen, paracetamol (acetaminophen), ketoprofen, aspirin (acetylsalicylic acid), and naproxen.
• the active ingredient is an anesthetic.
• the active ingredient is an antiinflammation agent.
• the active ingredient is a disinfectant.
• the active ingredient is an antibiotic. Examples of antibiotics include e.g. ampicillin, erythromycin, tetracycline, clarithromycin, penicillin, and metronidazole.
• the tablet comprises a combination of caffeine, L-theanine, vitamin B3, vitamin B6, and vitamin B12. In some embodiments of the invention, the tablet comprises a combination of caffeine, and vitamin B6. In some embodiments of the invention, the tablet comprises a combination of ginseng, and vitamin B12. In some embodiments of the invention, the tablet comprises a combination of melatonin, vitamin C, and zinc. In some embodiments of the invention, the tablet comprises a combination of L-theanine, and GABA. In some embodiments of the invention, the tablet comprises a combination of L-theanine, and bacopa.
• the active ingredient is a triptan.
• triptans include e.g. sumatriptan.
• the tablet generates more than 1.5 mL saliva within a period from 90 to 180 seconds from onset of mastication.
• the tablet generates more than 1.5 mL saliva within a period from 180 to 300 seconds from onset of mastication.
• the oral chewable tablet further comprises a saliva production inhibiting agent for controlling saliva production.
• the oral chewable tablet is designed to release the active ingredient in the oral cavity and designed to deliver a part of the active ingredient to the gastrointestinal tract as part of saliva generated upon mastication of the tablet.
• the content of disintegrants greatly facilitate disintegration of the tablet according to the invention.
• disintegrants have previously been used in tablet formulation science, the particular combination of disintegrants with dextrose according to the application would have been seen as problematic in view of the specific properties of dextrose.
• Various problems were suspected by the inventors of the present application, such as sensorial drawbacks and concentration issues with a high load of the active ingredients.
• the oral chewable tablet comprises one or more disintegrants selected from the group consisting of sodium croscarmellose, crospovidone, sodium starch glycolate, and combinations thereof.
• the unit weight of the tablet is from about 100 mg to about 2000 mg. In some embodiments of the invention, the unit weight of the tablet is from about 100 mg to about 1800 mg. In some embodiments of the invention, the unit weight of the tablet is from about 500 mg to about 1600 mg. In some embodiments of the invention, the unit weight of the tablet is from about 600 mg to about 1500 mg.
• the oral chewable tablet provides an improved melting sensation compared to an oral chewable tablet comprising less than 50% by weight of dextrose.
• the oral chewable tablet provides a less stickiness sensation compared to an oral chewable tablet comprising less than 50% by weight of dextrose. In some embodiments of the invention, the oral chewable tablet provides a less bitterness sensation from the one or more active ingredients compared to an oral chewable tablet comprising less than 50% by weight of dextrose.
• the oral chewable tablet is designed to turn into liquid within 15 seconds of mastication.
• the chewable tablet comprises at least two modules.
• a tablet comprising two or more modules will have module sizes which each are comparable to the volume of the complete tablet. Comparable in the present context means that the modules are not understood as small particles and a module should at least be greater than 1/20 of the complete tablet volume, preferably greater than 1/10 of the complete tablet volume.
• the oral tablet comprises a plurality of oral tablet modules.
• two modules are in particular advantageous as the use of dextrose may result in a more fragile tablet or at least the module in which the dextrose is present.
• dextrose may be present primarily in one module thereby optimizing the desired salivation and sensory experience from the module and the tablet as such whereas another module may serve as a support ensuring that the desired stability and friability of the complete tablet is obtained.
• the plurality of modules are slice-like layers.
• the term “slice-like” layer is a plain but very precise way of to the skilled person how a module may be provided, as such a layer is a standard structure obtained through conventional tableting procedures.
• Such application may e.g. include the use of a gum module and a non-gum module, where the non-gum modules are containing the dextrose particles.
• the non-gum layer may release the advantageous dextrose and the gum layer may both stabilize the tablet as described above but also interact with the dextrose during in particular the initial release for establishment of a very pleasant and impressing initial chew phase. This includes an increased saliva and moisture experience.
• said population of particles is tableted into a first module and combined with a second population of particles that is tableted into a second module, where the second population of particles is different from the first population of particles.
• the dextrose is evenly distributed in the tablet or at least one module of the tablet.
• One advantage of the above embodiment may be that the even distribution of the dextrose promotes an effective disintegration of the module upon mastication, e.g., due to lower mechanical strength contribution from the dextrose, thereby facilitating effective contacting of the resulting mastication fragments formed by the mastication with saliva, again increasing dissolving of the tablet. Also, the even distribution of the dextrose promotes a high number of mastication fragments with dextrose, which again effectively promotes salivation.
• the oral chewable tablet comprises a further tablet module with a different disintegration time.
• the one or more active ingredients is located in a first layer of the tablet.
• the one or more active ingredients is located in a second layer of the tablet. In some embodiments of the invention, the one or more active ingredients is both located in a first and a second layer of the tablet.
• one active ingredient is located in a first and another active ingredient is located in a second layer of the tablet.
• the one or more active ingredients is located in a first layer of the tablet and no active ingredients is located in a second layer of the tablet.
• the resistance to crunching of the tablet is greater than 60N, such as greater than 70N, such as greater than 80N, such as greater than 90N, such as greater than 100 N, such as greater than 110, such as greater than 13 ON such as greater than 150N, wherein the resistance to crunching of the tablet is less than 300N, such as less than 250N, such as less than 200N, wherein the resistance to crunching is determined according to European Pharmacopoeia 9.1, test method 2.9.8. by using a pharmaceutical resistance to crunching tester model Pharma Test type PTB 311.
• High intensity artificial sweetening agents can also be used alone or in combination with the above dextrose.
• Preferred high intensity sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside (natural intensity sweetener) and the like, alone or in combination.
• the tablet comprises flavor.
• the tablet comprises particles comprising gum base.
• the dextrose, one or more binders and one or more active ingredients are comprised in a first module and particles comprising gum base is comprised in a second module.
• the oral tablet comprises a first module and a second module, the first module comprising the dextrose, one or more binders and one or more active ingredients, the second module comprising particles comprising gum base.
• the dextrose, one or more binders and one or more active ingredients are tableted into a first module and particles comprising gum base is tableted into a second module, wherein the first module is free of gum base.
• the particles comprising gum base have an average particle size of at least 400 pm, such as between 400pm and 1400pm.
• the particles comprising gum base consists of gum base.
• the gum base particles consist of gum base, they typically have an average particle size between 800pm and 1400pm.
• the tablet comprises at least 20% by weight of gum base in a second module.
• the saliva generation may be tested using the following method:
• Table C*dex was melatonin available from JiaHerb. The tablets were pressed at 30 kN.
• Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below. In all of the tablet examples, the amount of the various ingredients is given as % by weight of the tablet.
• Table C*dex was calcium carbonate available from Nutrigranulation . The tablets were pressed at 30 kN.
• the dextrose tablets of Table 2 were made again as tablet numbers 100-2 A*, 100-2B*, 100-2C*, and 100-2D* replacing HPC with HPMC as binder.
• test persons gave a rating from “+” to “+++-1-1-”, where “+” is poor and “+++++” is excellent. “0“ indicated that it was not tested.
• “Liquid feeling” the impression of the tablet when placed in the mouth and chewed with respect to the sense of liquid in the mouth. For instance, if more liquid is sensed during and/or after chewing, then the score is high.
• “Mouthfeel” the overall impression of the tablet during chewing with respect to mouthfeel, including melting and tacking sensations.
• a high scoring mouthfeel is associated with a clean liquid (no sense of particles), no tablet residuals sticking in teeth and a creamy feeling (higher viscosity than water).
• a low scoring mouthfeel is associated with sense of particles in the liquid (incomplete dissolution), tablet residuals sticking in the teeth and a watery feeling of the liquid.
• “Overall taste” the overall impression of the taste of the tablet during chewing. For instance, if the taste was decreasing rapidly, a very low rating was given.
• the results reveal that the level of active ingredients had an impact on the system.
• the products were not sensorially acceptable. It is contemplated that below 50% of dextrose is unsuitable for the dextrose tablets. It was not expected that a high amount of active ingredients as used in a number of the examples were possible to add in the dextrose tablets without compromising the suitability of the dextrose tablets.
• examples 100-2B and 100-2C revealed beneficial sensorial properties even with the high amount of actives used. With respect to example 100-2D, the amount of actives compromised the sensorial properties of the dextrose tablets.
• HPC was a superior binder with resulting low friability as a function of the level of binder.
• HPMC was also a very good binder providing a good mouthfeel.
• Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, here including caffeine in an amount of 100 mg and optionally vitamin B premix in an amount of 15 mg as active ingredient. In all of the tablet examples, the amount of the various ingredients is given as % by weight of the tablet. Table 9: It was secured that the binders were thoroughly mixed into the dry mixture. *Dextrose was C*dexTM 02001 commercially available from Cargill. ***Caffeine available from Siegfried, ****Vitamin B premix available from DSM. The tablets were pressed at 27 kN.
• Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, here including vitamin C in an amount of 300 mg and optionally melatonin in an amount of 1.5 mg as active ingredient. In all of the tablet examples, the amount of the various ingredients is given as % by weight of the tablet.
• Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, here including L-theanine in an amount of 150 mg and optionally bacopa in an amount of 15 mg as active ingredient. In all of the tablet examples, the amount of the various ingredients is given as % by weight of the tablet. Table 9B: It was secured that the binders were thoroughly mixed into the dry mixture. *Dextrose was C*dexTM 02001 commercially available from Cargill. ***L-theanine available from Sichuan Tongsheng, ****Bacopa available from Network Nutrition. The tablets were pressed at 28 kN.
• Example 13 Composition of dextrose tablets with different active ingredients focused on immune stimulants
• Dextrose tablets based on the procedure in Example 1 were made with the formulations outlined in the examples below, here including active ingredients suitable for treating cough and cold symptoms. In all of these tablet examples, the total tablet weight is 1750 mg, and the amount of the various ingredients is given as mg. Table 11: It was secured that the binders were thoroughly mixed into the dry mixture. *Dextrose was C*dexTM 02001 commercially available from Cargill. **Dextrose was Emdex commercially available from JRS Pharma. ***Acetaminophen available from Mallinckrodt, ****Dextromethorphan HBr available from LGM Pharma, *****Phenylephrine HCl available from Siegfried. The tablets were pressed at 70 kN.
• dextrose tablet 100-4B was providing a superior mouthfeel and liquifying sensation compared to the commercially available product Airborne which contains the same type of actives as dextrose tablet 100-4B.

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