WO2022176981A1 - Préparation de film oral - Google Patents

Préparation de film oral Download PDF

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Publication number
WO2022176981A1
WO2022176981A1 PCT/JP2022/006666 JP2022006666W WO2022176981A1 WO 2022176981 A1 WO2022176981 A1 WO 2022176981A1 JP 2022006666 W JP2022006666 W JP 2022006666W WO 2022176981 A1 WO2022176981 A1 WO 2022176981A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
present
drug layer
water
oral film
Prior art date
Application number
PCT/JP2022/006666
Other languages
English (en)
Japanese (ja)
Inventor
明生 三輪
裕洋 山崎
遼 内冨
Original Assignee
大正製薬株式会社
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 大正製薬株式会社 filed Critical 大正製薬株式会社
Priority to JP2022540926A priority Critical patent/JP7168133B1/ja
Publication of WO2022176981A1 publication Critical patent/WO2022176981A1/fr

Links

Classifications

    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • HPMC2910 TC-5E, TC-5EW manufactured by Shin-Etsu Chemical Co., Ltd., kinematic viscosity of 2% by mass aqueous solution at 20 ° C.: 2.5 to 3.5 mPa s, average molecular weight: 16,000
  • HPMC2910 TC-5MW manufactured by Shin-Etsu Chemical Co., Ltd., kinematic viscosity of 2% by mass aqueous solution at 20 ° C.: 3.6 to 5.1 mPa s, average molecular weight: 22,000
  • HPMC2910 TC-5R, TC-5RW, TC-5RG manufactured by Shin-Etsu Chemical Co., Ltd., kinematic viscosity of 2% by mass aque
  • plasticizer used in the formulation of the present invention is not particularly limited as long as it is acceptable as a formulation and does not cause problems with the rapid dissolution, formulation stability and moldability of the formulation of the present invention.
  • plasticizers include glycerin, sesame oil, sorbitol, castor oil, propylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate 80 (polyoxyethylene (20) sorbitan oleate), polyethylene glycol [e.g., Macrogol 400 (Polymerization degree n of oxyethylene units is 7 to 9, the same applies hereinafter), Macrogol 600 (n is 11 to 13), Macrogol 1500 (n is an equal mixture of 5 to 6 and n is 28 to 36 ), Macrogol 4000 (n is 59 to 84), Macrogol 6000 (n is 165 to 210)] and the like.
  • Macrogol 400 Polymerization degree n of oxyethylene units is 7 to 9, the same applies hereinafter
  • Macrogol 600 n is 11 to
  • Polyethylene glycol also called macrogol, is a compound represented by H(OCH 2 CH 2 ) n OH (where n is 4 or more) and has a molecular weight of about 200 to 9,000.
  • macrogol 200, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, etc. are known.
  • the number after "macrogol” means the average molecular weight.
  • the above plasticizers can be used singly or in combination.
  • emulsifiers can be added to the formulation of the present invention, if necessary. These are not particularly limited as long as they are acceptable as a formulation and do not cause problems with the rapid dissolution, formulation stability and moldability of the formulation of the present invention. They can also be added to the drug layer or the non-drug layer, or both.
  • emulsifiers include alkylbenzenesulfonate, carrageenan, carboxyvinyl polymer, guar gum, glycerin fatty acid ester, sucrose fatty acid ester, stearic acid, lanolin, egg yolk lecithin, cetanol, sorbitan fatty acid ester, soybean lecithin, sorbitan trioleate, pectin, polyoxyethylene hydrogenated castor oil, sodium lauryl sulfate, lauromacrogol and the like.
  • pH adjusters include tartaric acid, citric acid, phosphoric acid and the like, and pharmaceutically acceptable salts thereof.
  • Sweeteners include, for example, aspartame, stevia, sucralose, glycyrrhizic acid and its pharmaceutically acceptable salts (e.g. alkali metal salts), thaumatin, acesulfame potassium, saccharin and its pharmaceutically acceptable salts ( For example, alkali metal salts) and the like.
  • the above sweeteners can be used singly or in combination.
  • flavoring agents include ascorbic acid, tartaric acid, citric acid, malic acid, and pharmaceutically acceptable salts thereof.
  • the above corrigents can be used alone or in combination.
  • Flavors include, for example, menthol, vanilla, orange, strawberry, raspberry, chocolate, grapefruit, cranberry, plum, kokuto, herbs, coffee, black tea, cinnamon, honey lemon, and the like.
  • coloring agents include yellow iron sesquioxide, brown iron oxide, caramel, black iron oxide, titanium oxide, iron sesquioxide, tar pigments, aluminum lake pigments, sodium copper chlorophyllin, and the like.
  • the content (% by mass) of luseogliflozin, a pharmaceutically acceptable salt thereof, or a hydrate thereof, which is an active ingredient determines the rapid dissolution, formulation stability, and although it is not particularly limited as long as there is no problem with moldability, it is preferably 6 to 20% by mass, more preferably 9 to 13% by mass, based on the entire formulation, Here, one more preferable content is 9 to 13% by mass, Another more preferable content is 9 to 11% by mass.
  • the content (% by mass) of the water-soluble polymer is not particularly limited as long as there is no problem with the quick solubility, formulation stability, and moldability of the formulation of the present invention. preferably 55 to 74% by mass, more preferably 58 to 71% by mass, Here, one more preferable content is 58 to 66% by mass, Another more preferable content is 67 to 71% by mass.
  • the content ratio of D-mannitol to candy is preferably 1:0.5 to 1:1.5, more preferably 1:0.8 to 1:1.2, still more preferably 1:0.8 to 1:1.2, based on mass. 1:1.0.
  • a content ratio of 1:0.8 to 1:1.2 is preferable.
  • a content ratio of 1:1.0 is more preferred.
  • the content (% by mass) of the plasticizer is not particularly limited as long as there is no problem with the rapid solubility, formulation stability, and moldability of the formulation of the present invention. 0 to 9% by mass, more preferably 0 to 6% by mass, Here, one more preferable content is 2 to 6% by mass, Another more preferable content is 0% by mass, that is, no plasticizer is included.
  • the formulation of the present invention comprises a drug layer and a non-drug layer.
  • a non-drug layer is provided on one side or both sides of the drug layer, and the preparation may have two or three layers.
  • the preparation of the present invention can also be an oral film preparation having a single-layer structure.
  • hydroxypropylcellulose is soluble in water, ethanol, and water-ethanol mixed solvents, and has the advantage that the solubility range can be selected from a wide range.
  • hydroxypropyl methylcellulose is a highly water-soluble polymer substance that is not easily affected by the humidity of the outside air. It has the advantage that it can be used as a support layer because it does not easily lose its physical strength.
  • Rapid dissolution is defined in accordance with the Japanese Pharmacopoeia dissolution test method 2nd method (paddle method) (test conditions: rotation speed 50 rpm, temperature: 37 ⁇ 0.5 ° C., test liquid: purified water, test liquid volume: 900 ml). A dissolution rate of 85% or more after 15 minutes.
  • Example 1 According to the formulation shown in Table 1-1, luseogliflozin hydrate and the components to be added were added to an appropriate amount of solvent (water-ethanol mixed solvent) and dissolved or dispersed by stirring to prepare a drug layer preparation solution. Similarly, a non-drug layer preparation solution was prepared. Next, the non-drug layer preparation solution was spread on a release film such as polyester and dried to form a film with an appropriate thickness. The drug layer preparation solution was spread and dried thereon to form a two-layer film. The oral film formulation was obtained by laminating the drug layers of the two films to form a three-layer film. The thickness of the oral film formulation was adjusted to 0.05 to 0.14 mm.
  • Comparative example 1 According to the formulation shown in Table 1-1, the oral film preparation was obtained by the method described in Example 1 or a method analogous thereto.
  • Example 1 The formulations of Examples and Comparative Examples are shown in Table 1 below.
  • the oral film preparations of the formulations described in Examples 2 to 14 and Comparative Examples 2 to 5 were produced by the method described in Example 1 or Comparative Example 1 or a method similar thereto.
  • Test example 1 Evaluation of Dissolution of Oral Film Preparations of Examples As evaluation of rapid dissolution, dissolution of each oral film preparation was evaluated according to the following procedure. The results are also shown in Table 1. The results were evaluated as "O” when dissolution of 85% or more was shown in 15 minutes, and as "X" when no dissolution was shown. According to the Japanese Pharmacopoeia dissolution test method 2 (paddle method), the paddle rotation number was 50, water was used as the test liquid, and the amount was determined by the HPLC method.
  • Table 1 show that the formulations of the present invention disclosed as examples satisfy the aforementioned requirements for rapid dissolution (dissolution rate of 85% or more in 15 minutes). Desirably, the dissolution of the evaluated formulation is 85% or more at 15 minutes.
  • Test example 2 Evaluation of Formulation Stability (Color Change) of Oral Film Preparations of Examples The formulation stability (color change) of each oral film preparation was evaluated according to the following procedure. The results are also shown in Table 1.
  • Example 13 produced less analogues.
  • the results described in Comparative Example 1 indicate that this formulation does not have a property of quick dissolution.
  • the results described in Comparative Example 2 indicate that the addition of crystalline cellulose to the formulation described in Comparative Example 1 caused a problem of formulation stability (discoloration).
  • the results described in Comparative Example 3 show that the addition of D-mannitol to the formulation described in Comparative Example 1 also caused the problem of formulation stability (discoloration).
  • the results described in Comparative Examples 4 and 5 indicate that the formulation stability (discoloration) problem also occurred due to the combination of crystalline cellulose and powdered hydrogenated maltose starch syrup.
  • Example 1 shows that the formulation stability (discoloration) problem was surprisingly solved by adding D-mannitol in addition to crystalline cellulose and powdered hydrogenated maltose starch syrup. It is shown that. As described above, the addition of D-mannitol in the formulation described in Comparative Example 3 poses a problem of formulation stability (discoloration).
  • Test example 4 Evaluation of Moldability of Oral Film Preparations of Examples The moldability of each oral film preparation was evaluated according to the following procedure. It was evaluated by a bending test. Specifically, the film formulation was manually folded up to 180°, and the state of the film formulation after releasing the hand was evaluated according to the following criteria. ⁇ : Not cracked after bending. x: Cracked after bending. All the preparations of the present invention disclosed as Examples in Table 1 did not crack after being folded (evaluation result: ⁇ ), and had no problem in formability.
  • the present invention has made it possible to provide an oral film preparation that contains luseogliflozin and has both rapid dissolution and formulation stability. Since this oral film preparation can be easily taken by rapidly dissolving in the oral cavity, it can be safely administered to the elderly and children.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention porte sur une préparation de film oral contenant de la luéogliflozine et permettant à la fois une dissolution rapide et une stabilité de préparation.　La présente invention concerne une préparation de film oral comprenant une couche médicamenteuse et une couche non médicamenteuse, la couche médicamenteuse étant caractérisée en ce qu'elle contient (a) luseogliflozine, un sel pharmaceutiquement acceptable de celle-ci, ou un hydrate desdites substances, (b) un polymère soluble dans l'eau, (c) de la cellulose cristalline, et (d) du sirop de maltose hydrogéné en poudre et du D-mannitol ; et la couche non médicamenteuse est caractérisée en ce qu'elle contient (e) un polymère soluble dans l'eau.
PCT/JP2022/006666 2021-02-19 2022-02-18 Préparation de film oral WO2022176981A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2022540926A JP7168133B1 (ja) 2021-02-19 2022-02-18 経口フィルム製剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021-025308 2021-02-19
JP2021025308 2021-02-19

Publications (1)

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WO2022176981A1 true WO2022176981A1 (fr) 2022-08-25

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WO (1) WO2022176981A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7504949B2 (ja) 2022-07-26 2024-06-24 Ｎｉｓｓｈａ株式会社 可食性フィルム及びその製造方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003097103A1 (fr) * 2002-05-16 2003-11-27 Kyukyu Pharmaceutical Co.,Ltd. Preparations de film rapidement soluble
JP2011246428A (ja) * 2010-05-26 2011-12-08 Nisshin Seiyaku Kk 口腔内崩壊型医薬品及びその製造方法
JP2013253038A (ja) * 2012-06-07 2013-12-19 Otsuka Pharmaceut Co Ltd 口腔内溶解型フィルム製剤
WO2014034842A1 (fr) * 2012-08-30 2014-03-06 大正製薬株式会社 Association d'un inhibiteur du sglt2 et d'un antihypertenseur
JP2016204347A (ja) * 2015-04-20 2016-12-08 高田製薬株式会社 モンテルカストナトリウム顆粒製剤
CN106539766A (zh) * 2015-09-18 2017-03-29 天津市汉康医药生物技术有限公司 鲁格列净片剂及其制备方法
CN106606488A (zh) * 2015-10-22 2017-05-03 天津市汉康医药生物技术有限公司 一种鲁格列净药物组合物及其制备方法
CN106727445A (zh) * 2016-12-21 2017-05-31 河北科技大学 一种达格列净口腔膜剂及其制备方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003097103A1 (fr) * 2002-05-16 2003-11-27 Kyukyu Pharmaceutical Co.,Ltd. Preparations de film rapidement soluble
JP2011246428A (ja) * 2010-05-26 2011-12-08 Nisshin Seiyaku Kk 口腔内崩壊型医薬品及びその製造方法
JP2013253038A (ja) * 2012-06-07 2013-12-19 Otsuka Pharmaceut Co Ltd 口腔内溶解型フィルム製剤
WO2014034842A1 (fr) * 2012-08-30 2014-03-06 大正製薬株式会社 Association d'un inhibiteur du sglt2 et d'un antihypertenseur
JP2016204347A (ja) * 2015-04-20 2016-12-08 高田製薬株式会社 モンテルカストナトリウム顆粒製剤
CN106539766A (zh) * 2015-09-18 2017-03-29 天津市汉康医药生物技术有限公司 鲁格列净片剂及其制备方法
CN106606488A (zh) * 2015-10-22 2017-05-03 天津市汉康医药生物技术有限公司 一种鲁格列净药物组合物及其制备方法
CN106727445A (zh) * 2016-12-21 2017-05-31 河北科技大学 一种达格列净口腔膜剂及其制备方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7504949B2 (ja) 2022-07-26 2024-06-24 Ｎｉｓｓｈａ株式会社 可食性フィルム及びその製造方法

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Publication number Publication date
JP7168133B1 (ja) 2022-11-09
JPWO2022176981A1 (fr) 2022-08-25

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