WO2021144625A1 - Composition synergique orale et son procédé de préparation - Google Patents

Composition synergique orale et son procédé de préparation Download PDF

Info

Publication number
WO2021144625A1
WO2021144625A1 PCT/IB2020/057280 IB2020057280W WO2021144625A1 WO 2021144625 A1 WO2021144625 A1 WO 2021144625A1 IB 2020057280 W IB2020057280 W IB 2020057280W WO 2021144625 A1 WO2021144625 A1 WO 2021144625A1
Authority
WO
WIPO (PCT)
Prior art keywords
solid oral
oral composition
agent
sodium
pyridoxine
Prior art date
Application number
PCT/IB2020/057280
Other languages
English (en)
Inventor
Vinay Sapte
Ganesh Giram
Original Assignee
Maneesh Pharmaceuticals Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Maneesh Pharmaceuticals Ltd filed Critical Maneesh Pharmaceuticals Ltd
Publication of WO2021144625A1 publication Critical patent/WO2021144625A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K9/0058—Chewing gums
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; 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
    • A61K9/2013—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

Definitions

  • the present invention relates to solid oral composition of doxylamine, pyridoxine in combination with natural extract as synergistic additive and pharmaceutically acceptable excipients.
  • the present invention also relates to solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients.
  • the present invention also relates to solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients, wherein the solid oral composition in the form of granules/ powder is filled into sachets or compressed into tablets, especially chew able tablets.
  • the present invention specifically relates to solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients for the treatment of nausea and vomiting.
  • the present invention specifically relates to solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive, wherein the composition comprising granulating agent, stabilizing agent, taste masking agent, bulking agents, solubilizer, viscosity increasing agent, disintegrants, glidants or lubricants, sweetening agents, preservatives, buffering agent, diluents and other pharmaceutically acceptable excipients.
  • the present invention more specifically relates to method for the preparation of oral solid composition comprising steps of sifting, mixing, granulating, dry mixing, wet milling, rasping, lubricating and sachet filling or compressing into tablets.
  • Oral powders, granules and liquids normally provide greater dosing flexibility than oral solid single-unit dosage forms. Oral powders and granules are having more surface area which exhibits quick release thereby more bioavailability of active ingredient in systemic circulation and showed more therapeutic efficacy than oral solid single-unit dosage forms.
  • the advantage with oral powders or granules is those having more physical and chemical stability when compare to liquid formulations which means less prone to microbial growth and these formulations having the greater dosing flexibility with reconstitution water or any another acceptable liquid.
  • Some oral solid single-unit dosage forms such as dispersible or effervescent preparations are intended to be dispersed, suspended or dissolved prior to administration.
  • Oral powders are the preparations consisting of solid, loose, dry particles of varying degrees of fineness. They contain one or more active ingredients, with or without excipients and, an authorized colouring matter and flavouring substances should be added if preferable. Oral powders are generally administered in or with water or another suitable liquid. They may also be swallowed directly and which are presented as single-dose or multi-dose preparations. Granules are preparations containing solid, dry aggregated groups of smaller powder particles, or individual larger particles that may have overall dimensions greater than lOOOpm.
  • the powder formulations have good chemical and physical stability, good application properties, user friendliness or good doing compliance, having good biological activity and enhanced efficacy combined with high selectivity.
  • Oral powders preparations can be supplied as oral powder sachets or tablets such as chewable tablets, wherein the granular powder composition can be filled into sachets or compressed into chewable tablets.
  • Doxylamine is a first- generation antihistamine and is a potent anticholinergic agent first reported in 1949 as sleep aid with weak hypnotic and calming effects. Doxylamine acts primarily as an antagonist or inverse agonist of the histamine HI receptor. This action is responsible for its antihistamine and sedative properties. To a lesser extent, doxylamine acts as an antagonist of the muscarinic acetylcholine receptors, an action responsible for its minor hypnotic, anticholinergic, and (at high doses) deliriant effects. Doxylamine in its succinic acid salt form in combination with vitamin B6 (pyridoxine) used to prevent morning sickness in pregnant women.
  • vitamin B6 pyridoxine
  • Doxylamine succinate is chemically, ethanamine, N, N-dimethyl-2-[l-phenyl- l-(2-pyridinyl)ethoxy]-, butanedioate (1:1).
  • the empirical formula is C 17 H 22 N 2 O C H 6 0 and the molecular mass is 388.46 g/mol, the structural formula is:
  • Doxylamine succinate is a white to creamy white powder, is an antihistamine with sedative and hypnotic properties. It is very soluble in water and alcohol, freely soluble in chloroform and very slightly soluble in ether and benzene.
  • Pyridoxine (also called pyridoxol) is one form of vitamin B6. Its hydrochloride salt, pyridoxine hydrochloride, is used as a vitamin B6 dietary supplement. Pyridoxine hydrochloride is a vitamin B6 analog.
  • the chemical name for pyridoxine hydrochloride is 3,4-pyridinedimethanol,5-hydroxy-6-methyl-, hydrochloride.
  • the empirical formula is C X H iN(3 ⁇ 4 ⁇ HO and the molecular mass is 205.64 g/mol and the structural formula is:
  • Pyridoxine HC1 is a white or practically white crystalline powder or crystals. Pyridoxine HC1 is freely soluble in water, slightly soluble in alcohol and insoluble in ether. Pyridoxine is one of the compounds analog with pyridoxal and pyridoxamine that are referred to as vitamin B6. Pyridoxine HC1 is used in oral vitamin supplements and injectable vitamin formulation products.
  • Ginger powder Ginger is the root or underground stem (rhizome) of the ginger plant Zingiber officinale belongs to Zingiberaceae family. Ginger plant is a flowering plant whose rhizome, ginger root or ginger, is widely used as a spice and a folk medicine. It is an herbaceous perennial grows annual pseudostems about one meter tall bearing narrow leaf blades. Ginger powder is used in food preparations intended primarily for pregnant or nursing women.
  • the present invention is an improvement over the prior art in that it delivers doxylamine succinate and pyridoxine hydrochloride in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients for the treatment of nausea and vomiting.
  • US Pat No. 6,340,695 B1 discloses the formulation comprising combination of doxylamine succinate and pyridoxine HC1, preferably in form of an enterically coated tablet, a medicament comprising synergistic duo of active ingredients is useful in the treatment of nausea and vomiting, during pregnancy “NVP”, wherein the “rapid onset” formulation comprising the following non- active excipients: a filler or binder, a disintegrating agent, a lubricant, a silica flow conditioner and a stabilizing agent, wherein the formulation exhibiting a dissolution profile indicative of a rapid onset.
  • US Pat No. 9,089,489 B2 discloses the dual release oral dosage system comprising doxylamine or analog, derivative, prodrug, metabolite and salt thereof and pyridoxine or analog, derivative, prodrug, metabolite and salt thereof, wherein said dual release oral dosage system comprising an immediate release component and delayed release component.
  • US Pub. No. 2007/0048367 A1 discloses herbal composition for treating morning sickness includes a mixture of vitamin B6, folic acid, ginger root extract, and red raspberry leaf.
  • US Pub. No. 2014/0335176 A1 discloses the disintegrant-free delayed release doxylamine succinate and pyridoxine HC1 formulation and a manufacturing process by using direct compression or dry granulation.
  • Doxylamine preparations are available typically in combination with Pyridoxine that may also contain folic acid.
  • Different combinations of Ginger and vitamin B6 (Pyridoxine) or combination of vitamin B6, vitamin B12 and folic acid are available in market. None of the prior-art reported the combination formulation comprising doxylamine or its salt, pyridoxine or its salt and in combination with natural extract such as ginger powder as synergistic additive, in the form of oral solid composition.
  • the main objective of the present invention is to provide solid oral composition of doxylamine, pyridoxine in combination with natural extract as synergistic additive and pharmaceutically acceptable excipients.
  • Another objective of the present invention is to provide solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients.
  • Another objective of the present invention is to provide solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients for the treatment of nausea and vomiting.
  • Another objective of the present invention is to provide solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients, wherein the solid oral composition in the form of granules/ powder is filled into sachets or compressed into tablets, especially chewable tablets.
  • Another objective of the present invention is to provide solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive, wherein the composition comprising granulating agent, stabilizing agent, taste masking agent, bulking agents, solubilizer, viscosity increasing agent, disintegrants, glidant or lubricants, sweetening agents, preservatives, buffering agent, diluents and other pharmaceutically acceptable excipients.
  • Still another objective of the present invention is to provide method for the preparation of oral solid composition comprising steps of sifting, mixing, granulating, dry mixing, wet milling, rasping, lubricating and sachet filling or compressing into tablets.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with natural extract as synergistic additive and pharmaceutically acceptable excipients.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients for the treatment of nausea and vomiting.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients, wherein the solid oral composition in the form of granules/ powder is filled into sachets or compressed into tablets, especially chew able tablets.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive, wherein the composition comprising granulating agent, stabilizing agent, taste masking agent, bulking agents, solubilizer, viscosity increasing agent, disintegrants, glidants or lubricants, sweetening agents, preservatives, buffering agent, diluents and other pharmaceutically acceptable excipients.
  • the present invention provides solid oral composition comprising of:
  • solubilizer or solubility enhancer 0.5% to 3.0% (w/w) of solubilizer or solubility enhancer
  • the present invention provides solid oral composition comprising of:
  • colloidal silicon dioxide 0.05% to 1.75 % (w/w) of colloidal silicon dioxide
  • croscarmellose sodium and sodium starch glycolate 1% to 5% (w/w) of croscarmellose sodium and sodium starch glycolate
  • the present invention provides method for the preparation of oral solid composition comprising steps of sifting, mixing, granulating, dry mixing, wet milling, rasping, lubricating and sachet filling or compressing into tablets.
  • the present invention provides a process for preparing solid oral composition, the process comprising steps of:
  • step (e) adding purified water to granulating agent for preparing slurry, then adding this slurry to mixture obtained form step (d),
  • Step (f) filter the obtained mixture or paste through the # 100 mesh nylon filter cloth and cooled to room temperature, (g) unloading Step (a) materials into Rapid mixer granulator and mixing upto 30 minutes at slow speed,
  • step (k) sifting of dried granules obtained from step (j) through #20 mesh, separating the passed and retained granules separately,
  • step (p) adding final lubricant to the above step (o) in blender and lubricate for 3 minutes, and
  • the present invention provides a process for preparing solid oral composition, the process comprising steps of:
  • step (d) adding and mixing polyvinyl pyrrolidone to the mixture obtained from the step (c) with stirring until to obtain clear mixture
  • step (e) adding purified water to maize starch for preparing slurry, then adding this slurry to mixture obtained form step (d),
  • step (k) sifting of dried granules obtained from step (j) through #20 mesh, separating the passed and retained granules separately,
  • step (p) adding final magnesium stearate to the above step (o) in blender and lubricate for 3 minutes, and (r) filling the required quantity of lubricated blend into sachet by automatic sachet filling machine in 4 ply aluminum laminates or foil or compressing the lubricated blend using 12.4 mm round punches into tablets, specifically chew able tablets.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with natural extract as synergistic additive and pharmaceutically acceptable excipients.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients for the treatment of nausea and vomiting.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive and pharmaceutically acceptable excipients, wherein the solid oral composition in the form of granules/ powder is filled into sachets or compressed into tablets, especially chew able tablets.
  • the present invention provides solid oral composition of doxylamine, pyridoxine in combination with ginger powder as synergistic additive, wherein the composition comprising granulating agent, stabilizing agent, taste masking agent, bulking agents, solubilizer, viscosity increasing agent, disintegrants, glidants or lubricants, sweetening agents, preservatives, buffering agent, diluents and other pharmaceutically acceptable excipients.
  • active ingredients are doxylamine, pyridoxine, ginger powder combination is effective in treatment of nausea and vomiting.
  • the “active ingredients” used in the present invention can be used as pharmaceutically acceptable salts.
  • the pharmaceutically acceptable salts used in the present invention are doxylamine in its succinate salt form as first active ingredient and pyridoxine in its hydrochloride salt form as second active ingredient.
  • the synergistic additive ginger powder is used in the present invention is obtained from market which is freely available.
  • the solid oral composition of the invention comprises first active ingredient is doxylamine succinate.
  • concentration of doxylamine succinate used in the solid oral composition of the invention is from 0.1% to 5%, preferably 3.6% (w/w).
  • the solid oral composition of the invention comprises second active ingredient is pyridoxine hydrochloride.
  • the concentration of pyridoxine hydrochloride used in the solid oral composition of the invention is from 0.1% to 5%, preferably 3.6% (w/w).
  • the solid oral composition of the invention comprises natural extract as synergistic additive is ginger powder.
  • the concentration of ginger powder used in the solid oral composition of the invention is from 30% to 56.5%, preferably 36.0% to 54% (w/w).
  • the solid oral composition according to the present invention comprise bulking agent or taste masking agent which includes mannitol, calcium carbonate, glycine, polydextrose, raffinose, sucralose, attapulgite, bentonite, carrageenan, Erythritol, glyceryl palmitostearate, neohesperidin dihydrochalcone, tributyl citrate.
  • the bulking agent or taste masking agent used in the solid oral composition is mannitol.
  • the concentration of bulking agent or taste masking agent used in the solid oral composition of present invention is from 10% to 18.5% (w/w). Most preferably used concentration of bulking agent or taste masking agent is from 13.5% to 18.5% (w/w).
  • the solid oral composition according to the present invention comprise solubilizer or solubility enhancer which includes cyclodextrin in its beta form, Hydroxypropyl Betadex, Sulfobutylether b-Cyclodextrin, Meglumine.
  • the solubilizer or solubility enhancer used in the solid oral composition is beta cyclodextrin.
  • the concentration of solubilizer or solubility enhancer used in the solid oral composition of present invention is from 0.5% to 3.0% (w/w). Most preferably used concentration of solubili er or solubility enhancer is from 0.9% to 2.7% (w/w).
  • the solid oral composition according to the present invention comprise viscosity increasing agent which includes but not limited to sodium carboxy methyl cellulose, polyvinyl pyrrolidone, carbomer, crosslinked polyacrylic acid polymers, gellan gum, xanthan gum and carrageenan.
  • the viscosity increasing agent used in the solid oral composition is polyvinyl pyrrolidone.
  • the concentration of viscosity increasing agent used in the solid oral composition of present invention is from 0.5% to 1.75% (w/w). Most preferably used concentration of viscosity increasing agent is from 0.9% to 1.62% (w/w).
  • the solid oral composition according to the present invention comprise granulating agent which includes acacia, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, pregelatinized starch, calcium sulfate, amylose, glycine, bentonite, ethylcellulose, disodium pyrosulfite, polyvinyl alcohol, gelatin, glucose, guar gum, magnesium aluminum silicate, maltodextrin, polyethylene oxide, polymethacrylates, povidone, sodium alginate, tragacanth, microcrystalline cellulose, maize starch and zein.
  • the granulating agent used in the solid oral composition is maize starch.
  • concentration of granulating agent used in the solid oral composition of present invention is from 0.1% to 1.5% (w/w). Most preferably used concentration of granulating agent is from 0.9% to 1.35% (w/w).
  • the solid oral composition according to the present invention comprise stabilizing agent which includes but not limited to calcium carbonate, colloidal silicone dioxide, microcrystalline cellulose, kaolin, activated charcoal, dibasic calcium phosphate, Bentonite, natural clay, activated alumina, zeolites and the like.
  • the stabilizing agent used in the solid oral composition is colloidal silicone dioxide.
  • the concentration of stabilizing agent used in the solid oral composition of present invention is from 0.05% to 1.75% (w/w). Most preferably used concentration of stabilizing agent is from 0.9% to 1.62% (w/w).
  • the solid oral composition according to the present invention comprise disintegrants which includes croscarmellose sodium, alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose (low substituted), microcrystalline cellulose, powdered cellulose, crospovidone, methylcellulose, polacrilin potassium, sodium alginate, sodium starch glycolate, starch, disodium disulfite, disodium edathamil, disodium edetate, disodiumethylenediaminetetraacetate (EDTA) crosslinked polyvinylpyrollidines, pregelatinized starch, carboxymethyl starch, sodium carboxymethyl starch, microcrystalline cellulose.
  • the disintegrants used in the solid oral composition is of one or more disintegrants includes crosscarmelose sodium and sodium starch glycolate.
  • concentration of disintegrants used in the solid oral composition of present invention is from 1% to 5% (w/w). Most preferably used concentration of disintegrants is from 2.7% to 4.45% (w/w).
  • the solid oral composition according to the present invention comprise glidant or lubricant which includes include calcium stearate, magnesium oxide, magnesium stearate, mineral oil, poloxamer, polyethylene glycol, sodium lauryl sulfate, sodium stearate fumarate, stearic acid, talc and, zinc stearate, glyceryl behanate, magnesium lauryl sulfate, boric acid, sodium benzoate, sodium acetate, combination of sodium benzoate and sodium acetate.
  • the glidant or lubricant used in the solid oral composition is magnesium stearate.
  • the concentration of glidant or lubricant used in the solid oral composition of present invention is from 0.5% to 2.5% (w/w). Most preferably used concentration of glidant or lubricant is from 1.35% to 2.25% (w/w).
  • the solid oral composition according to the present invention comprise sweetening agents which includes neotame, saccharin, aspartame, sucralose, thaumatin, acesulfame potassium, stevioside, stevia extract, paramethoxy cinnamic aldehyde, neohesperidyl dihydrochalcone and perillartine.
  • the sweetener used in the solid oral composition is neotame.
  • concentration of sweetening agents used in the solid oral composition of present invention is from 0.01% to 0.65% (w/w). Most preferably used concentration of sweetening agents is from 0.18% to 0.54% (w/w).
  • the solid oral composition according to the present invention comprise buffering agent which includes, citric acid, lactic acid, tartaric acid, sodium hydroxide, sodium dihydrogen phosphate and its hydrates, sodium phosphate and its hydrates, disodium hydrogen phosphate and its hydrates, disodium sulfate, sodium hydrogen sulfate, sodium carbonate, sodium hydrogen carbonate, calcium hydrogen carbonate.
  • buffering agent used in the solid oral composition is citric acid.
  • concentration of buffering agent used in the solid oral composition of present invention is from 0.01% to 0.65% (w/w). Most preferably used concentration of buffering agent is from 0.3% to 0.54% (w/w).
  • the solid oral composition according to the present invention comprise diluent or filler which includes cellulose or derivatives, modified cellulose, sodium carboxymethyl cellulose, ethyl cellulose hydroxymethyl cellulose, cellulose acetate, hydroxypropylcellulose, microcrystalline cellulose, dibasic calcium phosphate, sucrose, corn starch, potato starch and combinations thereof.
  • diluent diluent used in the solid oral composition is lactose.
  • concentration of diluent or filler used in the solid oral composition of present invention is from 5% to 35.5% (w/w). Most preferably used concentration of diluent or filler is from 5.54% to 34.45% (w/w).
  • the solid oral composition according to the present invention comprise preservative which include, parabens such as methyl paraben, propyl paraben, benzyl alcohol, sodium benzoate, phenol, benzalkonium chloride, thimerosal, chlorobutanol, benzoic acid, sodium bisulfite, and sodium proprionate.
  • preservative which include, parabens such as methyl paraben, propyl paraben, benzyl alcohol, sodium benzoate, phenol, benzalkonium chloride, thimerosal, chlorobutanol, benzoic acid, sodium bisulfite, and sodium proprionate.
  • the preservative used in the solid oral composition is methyl paraben.
  • concentration of preservative used in the solid oral composition of present invention is from 0.01% to 0.15% (w/w). Most preferably used concentration of preservative is from 0.045% to 0.135% (w/w).
  • solid oral composition comprising doxylamine succinate, pyridoxine hydrochloride and ginger powder
  • suitable volume container includes 4 ply aluminum foil sachet with different sizes ranges and the solid oral composition comprising doxylamine succinate, pyridoxine hydrochloride and ginger powder can be compressed into tablets, specifically chewable tablets.
  • the present invention provides a process for preparing solid oral powder composition or solid oral chewable tablet composition, the process comprising steps includes first active ingredient, second active ingredient, natural extract powder, stabilizing agent, diluent, bulking agent or taste masking agent, solubilizer or solubility enhancer, granulating agent were sifted through the sieve, purified water was added in SS Vessel and warmed and preservative is added and dissolved in the warm purified water with stirring, viscosity increasing agent is added and mixed with stirring until clear mixture obtained, purified water added to granulating agent for preparing slurry, then this slurry is added to previously obtained clear mixture, the obtained mixture or paste was filtered through the # 100 mesh nylon filter cloth and cooled to room temperature, unloaded sifted materials into Rapid mixer granulator and mixing upto 30 minutes at slow speed, granulated the obtained mixture by adding paste, obtained mixture passed through multimill fitted with 8 mm screen and wet mass is collected into fluidized bed dryer, wet granules

Landscapes

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

Abstract

La présente invention concerne une composition orale solide de doxylamine, pyridoxine en combinaison avec un extrait naturel en tant qu'additif synergique et excipients pharmaceutiquement acceptables. La présente invention concerne également une composition orale solide de doxylamine, pyridoxine en combinaison avec de la poudre de gingembre en tant qu'additif synergique et excipients pharmaceutiquement acceptables, la composition orale solide sous la forme de granulés/poudre étant introduite dans des sachets ou comprimée en comprimés, en particulier des comprimés à croquer. La présente invention concerne en outre une composition orale solide de doxylamine, pyridoxine en combinaison avec de la poudre de gingembre en tant qu'additif synergique et excipients pharmaceutiquement acceptables pour le traitement de la nausée et des vomissements. La présente invention concerne plus particulièrement un procédé de préparation d'une composition solide orale comprenant les étapes de tamisage, de mélange, de granulation, de mélange à sec, de broyage humide, de râpage, de lubrification et de remplissage en sachet ou de compression en comprimés.
PCT/IB2020/057280 2020-01-18 2020-07-31 Composition synergique orale et son procédé de préparation WO2021144625A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ININ202021002251 2020-01-18
IN202021002251 2020-01-18

Publications (1)

Publication Number Publication Date
WO2021144625A1 true WO2021144625A1 (fr) 2021-07-22

Family

ID=76863670

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2020/057280 WO2021144625A1 (fr) 2020-01-18 2020-07-31 Composition synergique orale et son procédé de préparation

Country Status (1)

Country Link
WO (1) WO2021144625A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2021225255B1 (en) * 2021-09-03 2022-06-16 Patel, Mihir MR Compositions, kits, and methods to provide synergistic and/or additive effects from comprised ingredients for the prevention, treatment and management of nausea and vomiting.

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2401185T3 (es) * 2004-09-27 2013-04-17 Sigmoid Pharma Limited Formulaciones de microcápsulas que comprenden dos ingredientes farmacéuticamente activos
US20190183141A1 (en) * 2017-12-14 2019-06-20 Hesson, LLC Systems and methods for modified confectionary items

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2401185T3 (es) * 2004-09-27 2013-04-17 Sigmoid Pharma Limited Formulaciones de microcápsulas que comprenden dos ingredientes farmacéuticamente activos
US20190183141A1 (en) * 2017-12-14 2019-06-20 Hesson, LLC Systems and methods for modified confectionary items

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NIEBYL JR: "Nausea and vomiting in pregnancy", NEW ENGLAND JOURNAL OF MEDICINE, vol. 363, no. 16, 14 October 2010 (2010-10-14), pages 1544 - 1550, DOI: 10.106/NEJMcpl003896 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2021225255B1 (en) * 2021-09-03 2022-06-16 Patel, Mihir MR Compositions, kits, and methods to provide synergistic and/or additive effects from comprised ingredients for the prevention, treatment and management of nausea and vomiting.
WO2023031779A1 (fr) * 2021-09-03 2023-03-09 PATEL, Natvarlal Hargovinddas Compositions, kits et procédés pour fournir des effets synergiques et/ou additifs à partir d'ingrédients composés pour la prévention, le traitement et la gestion de la nausée et des vomissements

Similar Documents

Publication Publication Date Title
TWI635863B (zh) 帕博西里之固態劑型
EP2068839B1 (fr) Composition pharmaceutique comprenant de la nilotinib ou son sel
EP3525766A1 (fr) Comprimés comprenant de 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)méthoxy)benzaldéhyde
JP4316013B2 (ja) エプロサルタン二水和物ならびにその製法および処方
PT1480622E (pt) Composições farmacêuticas em grânulos de libertação imediata e processo contínuo para as produzir
US8545879B2 (en) Fast disintegrating compositions of meloxicam
KR20130091319A (ko) 4-아미노-5-플루오로-3-[6-(4-메틸피페라진-1-일)-1ｈ-벤즈이미다졸-2-일]-1ｈ-퀴놀린-2-온 락테이트 일수화물을 포함한 제약 조성물
KR101977785B1 (ko) 에제티미브 및 로수바스타틴을 포함하는 경구용 복합제제 및 그 제조방법
JP2015527321A (ja) アルカリ化剤を含まないラキニモド製剤
CN104721230A (zh) 乳碱性蛋白与乳矿物盐的组合物及其制备方法和应用
TWI586353B (zh) Pharmaceutical preparations containing calcium antagonists and angiotensin II receptor antagonists
JP3586471B2 (ja) トラセミド含有医薬組成物
JPWO2020090970A1 (ja) 抗腫瘍剤を含む医薬組成物
JP2013533881A (ja) バノキセリンを含有する医薬組成物
WO2021144625A1 (fr) Composition synergique orale et son procédé de préparation
US9192615B2 (en) Method for the treatment of acne and certain dosage forms thereof
US20160008328A1 (en) Stable Pharmaceutical Package Comprising Azilsartan Medoxomil
JP2019530727A (ja) ラモトリギンを含む経口懸濁液用の粉末
CN110613692A (zh) 一种托匹司他片剂及其制备方法
WO2019012552A4 (fr) Compositions de composés organiques ferriques
CN118284415A (zh) 一种达罗他胺药物组合物及其制备方法和用途
US20180344648A1 (en) Clobazam tablet formulation and process for its preparation
TWI574705B (zh) Capsules
US8703188B1 (en) Dispersible tablet
JPWO2019230937A1 (ja) 溶出性に優れた経口固形製剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20913726

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20913726

Country of ref document: EP

Kind code of ref document: A1