WO2020036316A1 - Composition de suspension d'ibuprofène et forme posologique - Google Patents

Composition de suspension d'ibuprofène et forme posologique Download PDF

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Publication number
WO2020036316A1
WO2020036316A1 PCT/KR2019/008375 KR2019008375W WO2020036316A1 WO 2020036316 A1 WO2020036316 A1 WO 2020036316A1 KR 2019008375 W KR2019008375 W KR 2019008375W WO 2020036316 A1 WO2020036316 A1 WO 2020036316A1
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Prior art keywords
suspension composition
pharmaceutical
active ingredient
ibuprofen
packaging container
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PCT/KR2019/008375
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English (en)
Korean (ko)
Inventor
전준호
한상덕
김희은
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동아제약 주식회사
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Publication of WO2020036316A1 publication Critical patent/WO2020036316A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/1468—Containers characterised by specific material properties
    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to suspension compositions and dosage forms containing the active ingredient, and more particularly, to a suspension composition and dosage form of ibuprofen, which easily obtains an accurate dosage of the active ingredient and improves the convenience of the patient.
  • the present invention relates to pharmaceutical packages, kits and methods for making the same comprising the suspension composition and the dosage form.
  • Fever refers to a condition in which the body temperature rises above the normal range due to the action of the thermoregulatory center of the hypothalamus due to infection or inflammation. Pain refers to an uncomfortable sensation caused by stimulation of a particular nerve with a pain receptor. Treatment of fever and pain can be attempted in a variety of ways, depending on the cause. In particular, if the cause of the fever or pain is determined by determining the cause of the fever or pain, it may not be significant even if it is temporary or not. It is preferable to perform symptomatic therapy.
  • Ibuprofen is a compound with propionic acid derivatives in nonsteroidal anti-inflammatory drugs (NSAIDs), developed by Stewart Adam in 1961 and marketed under the name BURUFEN®. Advil®, Mortrin®, Nurofen It is sold under brand names, such as ®. Ibuprofen inhibits cyclooxygenase, which converts arachidonic acid to prostaglandin H2 (PGH2), and does not produce inflammatory mediators. Although some side effects such as nausea, indigestion, diarrhea and constipation are known, they are widely used as antipyretic analgesics in adults and children because of their effectiveness and safety, such as antipyretic, analgesic and anti-inflammatory effects.
  • NSAIDs nonsteroidal anti-inflammatory drugs
  • Ibuprofen is sold in various formulations such as tablets, liquid soft capsules, powders, and liquids.
  • various dosage forms can be selected depending on the convenience of taking, the speed of effect expression, and the taste of the consumer.
  • infants and children who have low swallowing ability and cannot tolerate bitter taste can be easily swallowed, have a viscosity, are difficult to spit, and are preferably administered in a suspension-type syrup formulation that can be masked and consumed with a sweet taste.
  • Suspended syrup formulation is a formulation in which ibuprofen is suspended in a syrup that contains a lot of sugar of Sucrose or High Fructose Corn Syrup. Because it is not dissolved, it can minimize the bitter taste caused by drugs. In addition, it has a high sugar content, so it has a strong preservation ability against bacteria, which is safe against microbial contamination in case of production or distribution, and its sweetness is strong to mask the bitter taste of some dissolved drugs, which is a good dosage form for infants and children.
  • Ibuprofen's suspension syrup products have been on the market for a long time, with many products available in multiple doses in a single plastic or glass container. Most of these products add synthetic preservatives such as propylparaben and methylparaben to cope with various environments where microorganisms can be contaminated after opening. Synthetic preservatives, such as propylparaben, have been known in many studies for the risk of endocrine toxicity, and some countries are restricting their use in foods.
  • Sachet packaging takes only one dose of liquid or powder packaged into a thin film-packing paper made of multilayered plastics, including aluminum, so that you don't have to worry about microbial contamination during use. It is a packaging form that has the advantage of not using synthetic preservatives such as parabens.
  • Low patient medication compliance is a commonly known problem. This depends on factors such as the volume of the liquid formulation to be administered, the particular active agent, the concentration of the drug and the surface activity, and includes the viscosity of the active ingredient in the drug formulation and the viscosity due to the formulation. Still other factors include the condition or condition being treated and whether the active agent is in solution or suspension.
  • the active agent generally has a viscosity of water or a higher solution or suspension viscosity, and as the viscosity increases, the time of administration and the amount remaining in the packaging container increase. If the formulation is a suspension, the additional energy required from the droplets containing suspended particulates results in longer discharge times and increased residual volume in the packaging machine than solution formulations with similar viscosities.
  • Fever usually lasts between 1 to 3 days and 3 to 7 days after the onset of the disease, so bottle-packed products for multiple doses cannot be used up or expire after opening the product. There are many cases. Therefore, there is an increasing need for a single-dose product that is only opened when there is a fever without using a preservative.
  • Korean Unexamined Patent Publication No. 10-2007-0085155 is a multilayer coated granule containing ibuprofen, having particles containing ibuprofen in the innermost layer, and containing alkyl acrylate-alkyl methacrylate copolymer, talc, and hydroxypropylmethylcellulose in the outer layer.
  • Coated granules containing ibufurophene having good controlled release properties in doses containing silicon dioxide and hydroxypropylcellulose in the layer and its outer layer are disclosed.
  • Korean Unexamined Patent Publication No. 10-2006-0130140 discloses a stable and aesthetically improved syrup comprising S (+)-ibuprofen, hydroxypropyl beta-cyclodextrin, at least one sweetener, water and optionally essential oils, and a preparation thereof have.
  • Korean Patent Laid-Open Publication No. 10-2006-0096492 describes a formulation for administering NSAID and acetaminophen in the form of a liquid suspension, which consists of a substantially immediate release one-part and enteric polymer upon contact of the dissolution medium with the pharmaceutical dosage form.
  • Pharmaceutical formulations are disclosed that are suitable for administration in the form of a suspension comprising two portions released in a release manner and having a therapeutic effect duration of at least 8 hours.
  • the present invention is to provide a suspension composition of ibuprofen and a dosage form thereof, which easily ensures an accurate dosage of the active ingredient and improves the patient's convenience of administration.
  • Another object of the present invention is to fill a unit dose, contain no preservatives or preservatives, and to fill a packaging container having an inner surface of various materials, for example, glass, aluminum, or polymer material, the inner layer of the packaging container. It is to provide a suspension composition of ibuprofen and a dosage form thereof to minimize the adsorption of the and to ensure that the target amount of active substance is administered without shaking during use.
  • the present inventors studied the dosage form which is easy to take the active substance even when taking without shaking, minimizing the interaction between the inner material of the film and the active substance when packed in a multi-layered film form of Sachet while containing ibuprofen as the active substance, As a result, the following composition was invented. It has been found that the composition of the present invention significantly eliminates the interaction between the film inner material and the active ingredient, so that the original dosage can be accurately administered without shaking.
  • a pharmaceutical suspension composition comprising a sugar or sugar alcohol, an active ingredient and silicon dioxide, wherein the active ingredient relates to a pharmaceutical suspension composition, which is ibuprofen, an isomer of ibuprofen, or a salt thereof.
  • Suspension compositions have low adhesion or adsorption to aluminum, glass or polymer materials, for example the adsorption can be up to 5% (w / v) of active substance administered.
  • the pharmaceutical suspension composition according to the present invention has the property that the dispersion stability is improved by making the dispersibility of the active ingredient constant.
  • a packaging container including an inner layer of aluminum, glass or polymer material
  • It relates to a pharmaceutical formulation, kit or package comprising a pharmaceutical suspension composition filled in the packaging.
  • the pharmaceutical formulations, unit dose containers, kits and methods described herein efficiently deliver a suspension composition comprising the active ingredient for treating a variety of diseases.
  • the pharmaceutical suspension composition according to the present invention comprises a) an active ingredient such as ibuprofen, stereoisomers of ibuprofen and salts thereof, b) at least one selected from the group consisting of sugars and sugar alcohols, and c) silicon dioxide do.
  • the active ingredient may be ibuprofen, an isomer of ibuprofen or a salt thereof, for example, the isomer of ibuprofen may be ibuprofen, dexibuprofen or ibuprofen lysine, and the salt of ibuprofen or ibuprofen It may be an acid or base addition salt of an isomer, for example sodium ibuprofen.
  • Ibuprofen has the chemical name Isobutylpropanoicphenolic acid, a representative nonsteroidal anti-inflammatory drug, and is known to have analgesic, antipyretic, anti-inflammatory and anti-inflammatory effects. Therefore, the composition according to the present invention is also used as an analgesic for pain, such as fever, headache, toothache, muscle pain and neuralgia due to cold.
  • Ibuprofen and isomers of the dexibuprofen and salts of the two components included in the present invention are 100% (w / v) of the total suspension composition in an amount that is convenient to administer to infants and children and exhibits sufficient pharmacological effect. More preferably, it is contained as 0.2 to 8.0% (w / v), 0.5 to 8.0% (w / v), 0.2 to 6.0% (w / v), or 0.5 to 6.0% (w / v) as a reference.
  • the composition according to the present invention comprises at least one selected from the group consisting of b) sugars and sugar alcohols.
  • the sugars and sugar alcohols included in the present invention impart sufficient viscosity in the suspension syrup and inhibit the microbial growth by inhibiting the water activity when present in high concentrations in the formulation, thereby eliminating microbial growth in the manufacturing process or distribution process as well. It gives a sweetness that can mask the bitter taste of the active ingredient, making it easy to administer.
  • the sugars that may be included in the present invention may be one or more selected from the group consisting of monosaccharides, disaccharides and oligosaccharides, for example sucrose, maltose, isomaltose, lactose, lactulose, trehalose, cerevis and There are monosaccharides such as disaccharides, fructose, galactose, glucose, and mannose, and may be one or more selected from the group consisting of these monosaccharides, and sugar alcohols include lactitol, maltitol, isomalt, galactitol, sorbitol, mannitol, and xylitol.
  • the oligosaccharides may include isomaltooligosaccharide, malto oligosaccharide, fructooligosaccharide, galactooligosaccharide and xylo oligosaccharide, and may be one or more selected from the group consisting of the oligosaccharides.
  • Preferred contents of the sugars and sugar alcohols which may be contained in the present invention are 3.0 to 95.0% (w / v) based on 100% (w / v) of the suspension composition, preferably 5.0 to 90.0% (w / v). Can be.
  • the composition according to the invention comprises c) silicon dioxide.
  • Silicon dioxide also called silica, is a very small particle with a large surface area, hydrophilic and lipophilic amphoteric properties, which makes it easy to disperse in aqueous solutions and also interacts with the active ingredient, which interacts with the inner material of the packaging. Rather than acting on adsorption, it acts to be well dispersed in suspension syrup.
  • the silicon dioxide which may be contained in the present invention should be sufficient to eliminate the adsorption of the active ingredient, for example 0.01 to 10% (w / v) based on 100% (w / v) of the suspension composition, preferably May be 0.01 to 6.0% (w / v).
  • composition according to the invention may comprise further compositions in addition to the compositions listed above.
  • it may further include one or more additives selected from the group consisting of viscosity modifiers, acidulants, suspending agents, surfactants, co-solvents, preservatives, flavoring agents, stabilizers and solvents.
  • Viscosity modifiers or suspending agents can be used to disperse solid particles evenly in a liquid, and may use gums such as guar gum and xanthan gum, and viscosity regulators such as hydroxypropyl cellulose, hydroxyethyl cellulose and polyethylene oxide
  • a mixture of microcrystalline cellulose and carboxymethylcellulose sodium such as Avicel RC591 can be used as an example.
  • the invention may also include acidulants or pH adjusting agents. pH adjusters can be used to reduce the solubility of the active ingredient to make the bitter taste less, or to make the pH acidic to ensure antiseptic ability against microorganisms.
  • the types and amounts of additional compositions according to various functions that may be included in the compositions of the present invention are well illustrated in the Handbook of Pharmaceutical Excipients 7th edition (Raymond C. Rowe).
  • the pharmaceutical composition according to the present invention is to minimize the adsorption of the ibuprofen active substance to the inner surface of the container by eliminating the interaction with the inner surface of the container so that the correct amount can be administered to the patient without shaking the container, so that the patient does not shake or shake gently This can prevent the situation where a small amount of active substance is administered.
  • Existing products do not shake due to the adsorption of the active material ibuprofen and the inner surface of the container there is a problem that can be administered less than the active material to be originally administered because some of the adsorbed active material is not discharged.
  • the pharmaceutical composition according to the present invention there is almost no difference between the suspension or the active ingredient discharged from the packaging container in the water vibration state (hand-shaking the packaging container) and in the non-vibration state (fixing state without shaking the packaging container by hand), The remaining amount in the packaging can be minimized. Therefore, there is an advantage that the target amount of the active substance can be administered without shaking when taking and can improve the convenience of taking the patient.
  • the content of the active ingredient remaining in the packaging container is 5.0% (w / v) or less, 4.5% (w / v) or less, 4.0% (w / v) or less, 3.5% (w / v) or less, or 2.0% (w / v) or less Can be.
  • the difference in the content of the active ingredient discharged in each of the vibration-free and water vibration state is less than 5% (w / v), 4.5 % (w / v) or less, 4.0% (w / v) or less, 3.5% (w / v) or less, 3.0% (w / v) or less, 2.5% (w / v) or less, or 2.0% (w / v) v) can be
  • the water vibration state of the packaging container may mean, for example, when the packaging container is shaken by hand for 10 seconds to 60 seconds, for example, 20 seconds to lower the adhesion or adhesion of the drug to the inner surface of the packaging container.
  • the packaging container included in the pharmaceutical preparation according to the present invention may preferably contain a single dose of the active ingredient since it is preferably a unit dose container of the drug.
  • the packaging container may be manufactured in various forms, for example, in the form of a pouch.
  • the pharmaceutical formulation, package or kit according to the invention is preferably a one-dose container of the active ingredient, ie a unit dose container.
  • a unit dose container When packaged in unit-dose containers, the single-use Sachet formulation is used only once, so there is no change in the quality of medicines due to microbial contamination after opening without the use of preservatives or preservatives that are harmful to the human body, and the remaining amount may be discarded due to the opening. There is no need for packaging, which has many advantages.
  • the packaging container may have a packaging form selected from the group consisting of Sachet, Stick or pouch.
  • the packaging container may be filled with 1 to 20 mL of a suspension composition containing the active ingredient, has a unit dosage of the drug formulation, and has a low internal surface area, so that the residual amount of the active ingredient in the container is low.
  • the active ingredient filled in the packaging container may be included in 5 to 80 mg per 1mL pharmaceutical suspension composition.
  • the content of the active ingredient remaining in the packaging after discharging the suspension composition from the packaging may be 6% (w / v) or less of the content of the active ingredient filled.
  • the unit dose container may be provided as a kit, which may be formed by packaging a plurality of individual unit dose containers or a plurality of containers together.
  • the packaging container includes a single layer or a multilayer polymer (polymer) layer, and the cavity inner layer of the container filled with the suspension composition or the active ingredient is PE, PP, EVA, EAA, EMAA, EEA, EMA, It comprises at least one polymer material selected from the group consisting of EMMA and PET, the inner layer may be made of a film layer.
  • the packaging material used in the present invention is selected from the group consisting of aluminum, PE, PP, EVA, EAA, EMAA, EEA, EMA, EMMA, and PET, as necessary, such as moisture or fragrance volatilization, surface design method, etc.
  • One or more polymers, paper, or the like may be combined to form and package a film in multiple layers.
  • the pharmaceutical formulation, package or kit according to the invention is packaged in a material having an inner surface of polyethylene, polypropylene or polyethylene copolymer as a single dose package.
  • the inner surface of the packaging material in the present invention is easy to heat adhesion, excellent heat resistance, chemical resistance, and should not be used a lot of plasticizers should be a safe material.
  • Polyethylene is a low density polyethylene and a high density polyethylene, but low density polyethylene is preferred because it is sufficiently warped and easy to squeeze out.
  • Polyethylene copolymers that can be used in the present invention include ethylene-vinylacetate copolymer (EVA), ethylene-acrylic acid copolymer (EAA), ethylene-methacrylic acid copolymer (EMAA), ethylene-ethylacrylate copolymer (EEA) , Ethylene-methyl acrylate copolymer (EMA), ethylene-methyl methacrylate (EMMA) and the like can be used.
  • EVA ethylene-vinylacetate copolymer
  • EAA ethylene-acrylic acid copolymer
  • EAA ethylene-methacrylic acid copolymer
  • EAA ethylene-ethylacrylate copolymer
  • EMA Ethylene-methyl acrylate copolymer
  • EMMA ethylene-methyl methacrylate
  • polypropylene which is inferior in workability but excellent in thermal stability and fire resistance, may be used as the inner material of the present invention.
  • composition according to the present invention eliminates the interaction with the inner packaging material, the active substance is not adsorbed on the wrapping paper, so that the exact amount may be administered even without administration.
  • precise amount can be administered even when divided administration without shaking to ensure excellent suspension stability of the active ingredient in the container. Consumer discomfort, which had to be shaken sufficiently before use, is reduced, allowing the medication to be administered comfortably.
  • Figure 1 compares the contents of ibuprofen obtained by discharging the contents of the stationary state without shaking after storage for 2 months in the accelerated test conditions of Examples 1-18 and Comparative Examples 1-10.
  • Figure 2 is a graph comparing the contents of ibuprofen remaining in the packaging material after the contents of the stationary state is discharged without shaking after storage for 2 months in the accelerated test conditions of Examples 1-18 and Comparative Examples 1-10.
  • Example 1-4 Formulations Containing Various Active Substances
  • the content of microcrystalline cellulose / sodium carboxymethyl cellulose, xanthan gum, silicon dioxide, citric acid and glycerin are the same, and the type and / or content of the active ingredient, sugar and / or sugar alcohol
  • microcrystalline cellulose / carboxymethyl cellulose sodium was added to purified water and homogenized at 5000 rpm for 5 minutes.
  • Xanthan gum was added and Homomixed again for 5 minutes.
  • Sucrose, D-sorbitol, glycerin, and silicon dioxide were added thereto, and warmed and homogenized to dissolve.
  • Ibuprofen, dexibuprofen, ibuprofen lysine and ibuprofen sodium were added, mixed by Homomixing, and the suspension composition was prepared by adjusting the capacity to 100 ml.
  • Example 5-11 Formulations Containing Various Contents of Silicon Dioxide
  • microcrystalline cellulose / carboxymethyl cellulose sodium was added to purified water and Homomixed at 5000 rpm for 5 minutes. Add xanthan gum and Homomix again for 5 minutes. Add sucrose, D-sorbitol, glycerin and various amounts of silicon dioxide, and heat it if necessary to homomix and dissolve. Ibuprofen was added, mixed by Homomixing, and adjusted to a volume of 100 ml to prepare a suspension composition.
  • Example 12-18 Formulations Using Packaging Machines of Various Inner Materials
  • a composition containing ibuprofen was prepared as the composition shown in Table 3 below. Specifically, microcrystalline cellulose / sodium carboxymethyl cellulose was added to purified water and homogenized at 5000 rpm for 5 minutes, xanthan gum was added, and then homogenized for 5 minutes. Sucrose, D-sorbitol, glycerin, and silicon dioxide were added thereto, and warmed and homogenized to dissolve. Ibuprofen was added, mixed by Homomixing, and the formulation was prepared by adjusting the dose to 100 ml.
  • the inner material of the packaging machine is LDPE (low density polyethylene), EVA (ethylene-vinylacetate copolymer), EMAA (ethylene-methacrylic acid copolymer), EEA (ethylene-acrylate copolymer), EMA (ethylene-methacrylate air)
  • LDPE low density polyethylene
  • EVA ethylene-vinylacetate copolymer
  • EMAA ethylene-methacrylic acid copolymer
  • EEA ethylene-acrylate copolymer
  • EMA ethylene-methacrylate air
  • the formulations of Examples 12 to 18 were prepared by filling 5 ml each of the compositions with a packaging paper which was a combination), EMMA (ethylene-methyl methacrylate copolymer) and PP (polypropylene).
  • the component content unit of Table 3 is w / v%.
  • Nurofen® a commercial formulation, was used as Comparative Example 1, and compositions of Examples 1 and 12 to 18 containing no silicon dioxide were used as Comparative Examples 2 to 9, and the silicon dioxide content in Example 5 was 0.005 w.
  • the composition prepared as / v% was compared with the composition according to the invention as Comparative Example 10.
  • the empty packaging machine was cut and put into 95% ethanol, and recovered ibuprofen using ultrasonic waves for 30 minutes, and the recovered solution was analyzed by HPLC. Indicated.
  • the content of ibuprofen shown in Table 4 is expressed in (w / v)% based on the amount to be included in the unit dosage form.
  • Example 12-18 having different inner materials of the packaging container were confirmed that the amount of ibuprofen discharged was almost constant, and there was no significant content difference even when the packaging machine was shaken or not shaken. This meant that the drug dosage was accurate because there was little adsorption between ibuprofen and the inner surface of the packaging machine.
  • Comparative Example 1 which is a drug package of Comparative Example 2-10 that uses the same inner material as the formulation of Example 12-18 but does not contain silicon dioxide and a commercial drug, 7-15% (w / v) of ibuprofen is adsorbed on the inner surface of the packaging, so that the drug was released without shaking the packaging machine, it was confirmed that the active ingredient of the exact content indicated is not administered.

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Abstract

La présente invention concerne une suspension contenant de l'ibuprofène et, plus spécifiquement : une composition de suspension pharmaceutique permettant l'administration d'une quantité précise d'une substance active même si un patient ne secoue pas la composition de suspension pharmaceutique lors de la prise ; un agent pharmaceutique dans lequel un récipient d'emballage comprenant une couche interne d'aluminium, de verre ou d'un polymère est chargé avec la composition de suspension pharmaceutique ; et son procédé de fabrication.
PCT/KR2019/008375 2018-08-14 2019-07-08 Composition de suspension d'ibuprofène et forme posologique WO2020036316A1 (fr)

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KR1020180095051A KR102145022B1 (ko) 2018-08-14 2018-08-14 이부프로펜의 현탁액 조성물 및 투여 제형
KR10-2018-0095051 2018-08-14

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20010042197A (ko) * 1998-03-27 2001-05-25 클래스 하인츠-게르트 경구용 활성제 현탁액
US20030157172A1 (en) * 2001-12-20 2003-08-21 Lu Guang Wei Pharmaceutical suspension for oral administration
KR20090023607A (ko) * 2006-05-19 2009-03-05 노르브룩 래보러토리 리미티드 안정한 수성현탁액
WO2009083759A1 (fr) * 2008-01-03 2009-07-09 Wockhardt Research Centre Suspension pharmaceutique orale contenant du paracétamol et de l'ibuprofène

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0347134A (ja) * 1989-03-08 1991-02-28 Hoechst Japan Ltd ヒドロゲル製剤およびキセロゲル製剤の製造法
ES2134796T3 (es) * 1992-12-01 1999-10-16 Spirig Ag Pharmazeutische Prap Composiciones farmaceuticas que contienen s(+)-ibuprofeno.
CZ297830B6 (cs) * 2005-08-30 2007-04-11 I.Q.A., A. S. Zpusob výroby jemne krystalické smesi obsahující nesteroidní protizánetlivé lécivo, jemne krystalická smes pripravitelná tímto zpusobem a pevný farmaceutický prostredek tuto smes obsahující

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20010042197A (ko) * 1998-03-27 2001-05-25 클래스 하인츠-게르트 경구용 활성제 현탁액
US20030157172A1 (en) * 2001-12-20 2003-08-21 Lu Guang Wei Pharmaceutical suspension for oral administration
KR20090023607A (ko) * 2006-05-19 2009-03-05 노르브룩 래보러토리 리미티드 안정한 수성현탁액
WO2009083759A1 (fr) * 2008-01-03 2009-07-09 Wockhardt Research Centre Suspension pharmaceutique orale contenant du paracétamol et de l'ibuprofène

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NYARKO-SEFAH, N. Y.: "Standardisation of oral liquid ibuprofen suspension for improved stability and efficacy", PH.D. THESIS, 23 January 2017 (2017-01-23), pages 1 - 109, XP055687289 *

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