WO2017146106A1 - Procédé de production d'un patch pour la cavité buccale - Google Patents

Procédé de production d'un patch pour la cavité buccale Download PDF

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Publication number
WO2017146106A1
WO2017146106A1 PCT/JP2017/006633 JP2017006633W WO2017146106A1 WO 2017146106 A1 WO2017146106 A1 WO 2017146106A1 JP 2017006633 W JP2017006633 W JP 2017006633W WO 2017146106 A1 WO2017146106 A1 WO 2017146106A1
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WO
WIPO (PCT)
Prior art keywords
layer
drug
tableting pressure
powder
tableting
Prior art date
Application number
PCT/JP2017/006633
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English (en)
Japanese (ja)
Inventor
利博 中西
靖久 古瀬
隆明 義永
Original Assignee
久光製薬株式会社
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.)
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Publication date
Application filed by 久光製薬株式会社 filed Critical 久光製薬株式会社
Priority to JP2018501739A priority Critical patent/JP6548809B2/ja
Publication of WO2017146106A1 publication Critical patent/WO2017146106A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4425—Pyridinium derivatives, e.g. pralidoxime, pyridostigmine
    • 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
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • the present invention relates to a method for producing an intraoral patch.
  • This application claims priority based on Japanese Patent Application No. 2016-034522 for which it applied to Japan on February 25, 2016, and uses the content here.
  • Patent Document 1 discloses a tablet for use as an intraoral patch comprising two layers, a drug layer and an adhesive layer, which is applied to an oral mucosa such as a palate.
  • Such a bilayer tablet (laminated tablet) can be produced using a known laminated tableting machine. First, the first layer powder is filled into a mortar and lightly compressed with an upper punch and a lower punch. Subsequently, the second layer powder is overlaid and filled on the first layer powder compressed in the die, and lightly compressed with an upper punch and a lower punch. Finally, the compressed first layer powder and second layer powder are strongly compressed with the upper and lower eyelids to obtain a bilayer tablet.
  • the drug layer as the first layer is blended with an elution control component for continuously eluting the drug at a ratio of 10% by mass or more, and the adhesive layer as the second layer.
  • An adhering component for adhering the preparation to the oral mucosa is blended in a proportion of 25 to 75% by mass.
  • the elution control component is, for example, hydroxypropylcellulose or hypromellose.
  • the adhering component is, for example, carmellose sodium or povidone.
  • the elution control components such as hydroxypropylcellulose and hypromellose are powders with good moldability, but the adhering components such as carmellose sodium and povidone are powders with poor moldability. For this reason, the moldability is greatly different between the tableting powder of the first layer and the tableting powder of the second layer. In the production of a two-layer tablet, if the moldability of each layer is different, compression molding of each layer works preferentially, the adhesive force at the boundary surface between both layers becomes weak, and delamination tends to occur.
  • the present invention has been made in view of the above circumstances, and an object thereof is to provide a method for producing an intraoral patch capable of reducing the occurrence of delamination between a drug layer and an adhesive layer. To do.
  • the method for producing an oral patch is at least selected from the group consisting of hydroxyalkylalkylcellulose, hydroxypropylcellulose, sodium carboxyalkylcellulose, ethylcellulose, hydrogenated castor oil, and sucrose fatty acid ester.
  • a method for producing an oral patch comprising a drug layer comprising a single drug release controlling agent, and an adhesive layer containing carboxyalkyl cellulose or a carboxyalkyl cellulose salt and polyvinylpyrrolidone as an adhesive. Then, the first layer powder constituting the drug layer is filled in the die of a tableting machine, and the drug layer is formed by compressing the first layer powder with a tableting pressure of 0.2 to 1.2 kN.
  • the second layer powder constituting the adhesion layer is filled on the drug layer in the die, and the drug layer and The second layer powder is compressed with a tableting pressure of 6.0 to 26 kN to form the adhesive layer, and the drug layer and the adhesive layer are compressed with a tableting pressure of 7.5 to 26 kN. To do.
  • the diameter of the oral patch in which the drug layer and the adhesive layer are compressed with a tableting pressure of 7.5 to 26 kN is the thickness of the oral patch. It may be 4 times or more.
  • the occurrence of delamination between the drug layer and the adhesive layer can be reduced.
  • the intraoral patch includes a drug layer and an adhesive layer.
  • the drug layer contains a drug release controlling agent consisting of at least one selected from the group consisting of hydroxyalkylalkylcellulose, hydroxypropylcellulose, sodium carboxyalkylcellulose, ethylcellulose, hydrogenated castor oil, and sucrose fatty acid ester.
  • the compounding amount of the drug release controlling agent is not particularly limited as long as it can delay the dissolution of the drug from the drug layer or the collapse of the drug layer.
  • the content of the drug release controlling agent is 10% by mass or more based on the total mass of the components of the drug layer.
  • the drug layer includes a pH regulator, a refreshing agent such as l-menthol, a sweetener, a corrigent, a coloring agent, an adsorbent, a stabilizer, a flavoring agent (fragrance), and the like. It may contain components.
  • the adhesion layer usually contains an adhesive as a component that adheres to the oral mucosa.
  • the adhesion layer comprises, as an adhesion agent, a group consisting of carboxyalkyl cellulose, carboxyalkyl cellulose salt, alginic acid, alginate, poly (N-vinyl lactam), polyvinyl alcohol, hydroxypropyl cellulose, carboxyvinyl polymer, pullulan and pregelatinized starch. Contains at least one selected.
  • the adhesion layer contains carboxyalkyl cellulose or carboxyalkyl cellulose salt and polyvinyl pyrrolidone as an adhesion agent.
  • the content of the adhesive is preferably 25 to 75% by mass based on the total mass of the adhesive layer components.
  • the intraoral patch according to this embodiment is a tablet, which is a two-layer tablet (laminated tablet) composed of two layers of a drug layer and an adhesive layer.
  • the intraoral patch is formed in a thin disk shape having a substantially circular outer periphery, and both the front surface and the back surface thereof are formed flat.
  • the thickness of the oral patch is, for example, 1.0 to 2.5 mm, preferably 1.5 to 2.0 mm. Among them, the thickness of the drug layer as the first layer is 0.67 to 1.67 mm, and the thickness of the adhesion layer as the second layer is 0.33 to 0.83 mm.
  • the diameter of the oral patch is, for example, 5 to 15 mm, preferably 7 to 10 mm.
  • the intraoral patch according to the present embodiment is preferably formed as thin as possible in consideration of ease of application in the oral cavity and less uncomfortable feeling when applied.
  • a shape is represented by a ratio of diameter to thickness (diameter / thickness), it is approximately 4 or more.
  • the drug layer and adhesive layer of the tablet further contain components commonly used in tablets such as excipients such as lactose hydrate, binders such as crystalline cellulose, and lubricants such as stearate and talc. You may do it.
  • excipients such as lactose hydrate
  • binders such as crystalline cellulose
  • lubricants such as stearate and talc. You may do it.
  • FIG. 1 is a diagram showing a method for producing an intraoral patch 30 according to this embodiment.
  • (A) to (e) of FIG. 1 show each step of tableting.
  • the first layer powder 10 constituting the drug layer 11 and the second layer powder 20 constituting the adhesion layer 21 are prepared.
  • each component is weighed based on a predetermined blending ratio and mixed to obtain a first layer powder 10 which is a tableting powder for the first layer.
  • each component is weighed based on a predetermined
  • These first layer powder 10 and second layer powder 20 are respectively set in the hopper of the tableting machine 1.
  • the tableting machine 1 compresses the first layer powder 10 and the second layer powder 20.
  • the first layer powder 10 is filled into the die 2 from the hopper of the tableting machine 1 (see FIG. 1A).
  • the first layer powder 10 is compressed with a tableting pressure (first tableting pressure) of 0.2 to 1.2 kN by the upper punch 3 and the lower punch 4 of the tableting machine 1 to form the drug layer 11 (FIG. 1 (b)).
  • the second layer powder 20 is filled onto the drug layer 11 in the die 2 from the hopper of the tableting machine 1 (see FIG. 1C).
  • the upper layer 3 and the lower layer 4 are used to compress the second layer powder 20 with a tableting pressure (second tableting pressure) of 6.0 to 26 kN to form the adhesion layer 21 (see FIG. 1 (d)).
  • the drug layer 11 and the adhesive layer 21 are compressed by the upper punch 3 and the lower punch 4 with a tableting pressure (third tableting pressure) of 7.5 to 26 kN.
  • the intraoral patch 30 can be manufactured (refer FIG.1 (e)).
  • Example 1 In this example, the ranges of the first tableting pressure and the second tableting pressure were examined by changing the magnitudes of the first tableting pressure and the second tableting pressure to reduce delamination.
  • Example formation procedure Varying tablet pressures of the first tableting pressure and second tableting pressure were changed to produce tablets for oral patch of sample numbers A1 to A60.
  • each component shown in Table 1 was weighed and mixed based on the respective blending ratios to obtain a first layer powder.
  • the adhesion layer each component shown in Table 1 was weighed based on the blending ratio and mixed to obtain a second layer powder.
  • the first layer powder and the second layer powder were set in a tableting machine, and tableting was performed by the process shown in FIG.
  • evaluation results The evaluation results for each sample number are shown in Table 2. As shown in Table 2, when the first tableting pressure was 1.4 kN or more, the evaluation criteria were not satisfied regardless of the magnitude of the second tableting pressure. When the first tableting pressure was 1.0 to 1.2 kN, the degree of delamination varied depending on the magnitude of the second tableting pressure. When the first tableting pressure was 0.8 kN or less, the evaluation criteria were satisfied regardless of the magnitude of the second tableting pressure.
  • the second layer powder is stacked without compressing the first layer powder, so that the layer interface between the first layer and the second layer is disturbed in the two-layer tablet. End up. Since this is not preferable in appearance, this condition is not suitable as a manufacturing condition.
  • the upper limit of the second tableting pressure is 26 kN due to the allowable pressure limit of the punch of the tableting machine.
  • the first tableting pressure is 0.2 to 1.2 kN
  • the second tableting pressure is 5 to 26 kN
  • the third tableting pressure is 18.5 kN.
  • Example 2 In the present example, the range of the second tableting pressure and the third tableting pressure that can reduce delamination was examined by changing the magnitudes of the second tableting pressure and the third tableting pressure and using the friability as an index.
  • Example formation procedure Varying tablet pressures of the second tableting pressure and third tableting pressure were changed to produce tablets for oral patch of sample numbers B1 to B7.
  • each component shown in Table 3 was weighed based on the blending ratio and mixed to obtain a first layer powder.
  • each component shown in Table 3 was weighed based on the blending ratio and mixed to obtain a second layer powder.
  • the first layer powder and the second layer powder were set in a tableting machine, and tableting was performed by the process shown in FIG.
  • Example numbers B1 to B7 of the oral patch consisting of two layers having a diameter of 8 mm, a drug layer thickness of 1.3 mm, and an adhesive layer thickness of 0.6 mm.
  • the friability (mass percentage of reduced mass with respect to the initial mass) was measured according to the “Tablet friability test method” described in the reference information of the 16th revision Japanese Pharmacopoeia. Using the friability as an index, delamination was evaluated based on the following evaluation criteria. ⁇ : Abrasion degree is 3.0% or less ⁇ : Abrasion degree exceeds 3.0%
  • the first tableting pressure is 1.0 kN
  • the second tableting pressure is 6.0 to 26 kN
  • the third tableting pressure is 7.5 to 26 kN.
  • the first tableting pressure is 0.2 to 1.2 kN
  • the second tableting pressure is 6.0 to 26 kN
  • the third The tableting pressure is 7.5 to 26 kN.
  • the tablets produced in Example 1 and Example 2 described above have a diameter of 8 mm and a thickness of 1.9 mm (the sum of the drug layer thickness of 1.3 mm and the adhesive layer thickness of 0.6 mm). .
  • it is a thin disc-shaped bilayer tablet having a diameter of 4 times or more with respect to the thickness, it is difficult to cause delamination by applying the method for producing an oral patch according to the above-described embodiment.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
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Abstract

L'invention concerne un procédé de production d'un patch pour la cavité buccale comprenant une couche de médicament et une couche adhésive, et qui consiste : à installer une première couche de poudre, qui constitue la couche de médicament, dans le mortier d'une machine de compression ; à comprimer la première couche de poudre avec une pression de compression comprise entre 0,2 et 1,2 kN pour former la couche de médicament ; à ajouter une seconde couche de poudre, qui constitue la couche adhésive, sur la couche de médicament à l'intérieur du mortier ; à comprimer la couche de médicament et la poudre de la seconde couche avec une pression de compression comprise entre 6,0 et 26 kN pour former la couche adhésive ; et à comprimer la couche de médicament et la couche adhésive avec une pression de compression comprise entre 7,5 et 26 kN.
PCT/JP2017/006633 2016-02-25 2017-02-22 Procédé de production d'un patch pour la cavité buccale WO2017146106A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2018501739A JP6548809B2 (ja) 2016-02-25 2017-02-22 口腔内貼付剤の製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016034522 2016-02-25
JP2016-034522 2016-02-25

Publications (1)

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WO2017146106A1 true WO2017146106A1 (fr) 2017-08-31

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PCT/JP2017/006633 WO2017146106A1 (fr) 2016-02-25 2017-02-22 Procédé de production d'un patch pour la cavité buccale

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TW (1) TW201804988A (fr)
WO (1) WO2017146106A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006527184A (ja) * 2003-06-06 2006-11-30 エティファーム 口腔内分散性多層錠剤
WO2014192918A1 (fr) * 2013-05-31 2014-12-04 久光製薬株式会社 Timbre pour cavité buccale

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006527184A (ja) * 2003-06-06 2006-11-30 エティファーム 口腔内分散性多層錠剤
WO2014192918A1 (fr) * 2013-05-31 2014-12-04 久光製薬株式会社 Timbre pour cavité buccale

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Publication number Publication date
JP6548809B2 (ja) 2019-07-24
TW201804988A (zh) 2018-02-16
JPWO2017146106A1 (ja) 2018-09-20

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