JP-7854897-B2 - Film-coated granules, formulations containing the same, and methods for producing the same.

JP7854897B2JP 7854897 B2JP7854897 B2JP 7854897B2JP-7854897-B2

Inventors

尾曲克彦
高田新也
木全崚太
吉原尚輝

Assignees

沢井製薬株式会社

Dates

Publication Date: 20260507
Application Date: 20220819
Priority Date: 20210910

Claims (17)

It comprises core particles containing a molten component and a film disposed on the surface of the core particles, The aforementioned film is a film-coated granule comprising a porous material, a plasticizer, and a polymer.
The film-coated granules according to claim 1, wherein the plasticizer is selected from plasticizers that can be positioned between the molecules of the polymer.
The film-coated granules according to claim 1, wherein the plasticizer is one or more selected from the group consisting of triethyl citrate, polyethylene glycol, propylene glycol, triacetin, and tributyl acetyl citrate, and the polymer is one or more selected from the group consisting of hypromellose acetate succinate, hydroxypropyl cellulose, ethyl cellulose, vinyl acetate, methacrylic acid copolymer L, ammonia alkyl methacrylate copolymer, and methacrylic acid copolymer S.
The film-coated granules according to claim 1, wherein the core particles comprise a core material, a molten component layer disposed on the surface of the core material, and an active pharmaceutical ingredient-containing layer disposed on the surface of the molten component layer.
The aforementioned core particle comprises the active pharmaceutical ingredient and a molten component. The film-coated granules according to claim 1, wherein the active pharmaceutical ingredient and the molten component are bound together.
The aforementioned nuclear particle further contains a polymer, The film-coated granules according to claim 5, wherein the active pharmaceutical ingredient, the molten component, and the polymer are bound together.
The film-coated granules according to claim 1, wherein the film further comprises one or more pharmaceutically acceptable first additives.
A film-coated granule according to any one of claims 1 to 7, A formulation comprising one or more pharmaceutically acceptable second excipients.
By adsorbing a plasticizer onto a porous material, The porous material on which the plasticizer has been adsorbed is adsorbed onto core particles containing molten components to obtain first particles. A method for producing film-coated granules, comprising adsorbing a polymer onto the first particles to form a film on the core particles comprising the porous material, the plasticizer, and the polymer.
The polymer is adsorbed onto the first particles at a first temperature. A method for producing film-coated granules according to claim 9, wherein the film is formed on the nucleus particles at a second temperature equal to or higher than the first temperature.
The method for producing film-coated granules according to claim 9, wherein the plasticizer is selected from plasticizers that can be positioned between the molecules of the polymer.
The method for producing film-coated granules according to claim 9, wherein the plasticizer is one or more selected from the group consisting of triethyl citrate, polyethylene glycol, propylene glycol, triacetin, and tributyl acetyl citrate, and the polymer is one or more selected from the group consisting of hypromellose acetate succinate, hydroxypropyl cellulose, ethyl cellulose, vinyl acetate, methacrylic acid copolymer L, ammonia alkyl methacrylate copolymer, and methacrylic acid copolymer S.
The molten component is adsorbed onto the nuclear material to form a molten component layer. The active pharmaceutical ingredient is adsorbed onto the aforementioned molten component. A method for producing film-coated granules according to claim 9, comprising forming an active pharmaceutical ingredient-containing layer comprising the molten component and the active pharmaceutical ingredient to obtain the core particles.
The molten component and the active pharmaceutical ingredient are bound together. A method for producing film-coated granules according to claim 9, comprising obtaining the core particles containing the molten component and the active pharmaceutical ingredient.
The molten component, the active pharmaceutical ingredient, and the polymer are bonded together. A method for producing film-coated granules according to claim 9, comprising obtaining the core particles comprising the molten component, the active pharmaceutical ingredient, and the polymer.
A method for producing film-coated granules according to claim 9, wherein one or more pharmaceutically acceptable lubricants are further added when forming the film on the nucleus particles.
A method for producing a pharmaceutical formulation, comprising mixing film-coated granules obtained by the method for producing film-coated granules according to any one of claims 9 to 16 with one or more pharmaceutically acceptable second additives, and then compressing the mixture into tablets.

Description

One embodiment of the present invention relates to film-coated granules. Alternatively, one embodiment of the present invention relates to a formulation containing film-coated granules. Alternatively, one embodiment of the present invention relates to a method for producing film-coated granules. Alternatively, one embodiment of the present invention relates to a method for producing a formulation containing film-coated granules. In pharmaceutical formulations, coatings are used for various purposes, such as controlling drug dissolution (e.g., gastric soluble, enteric coated, sustained-release) and masking the bitter taste of drugs. Coating methods are broadly classified into dry and wet methods. Wet methods generally require a considerable amount of manufacturing time for solvent spraying and drying. Furthermore, in wet methods, the solvent can adversely affect the stability of the drug. Therefore, for example, Patent Document 1 describes a solvent-free method in which a mixture of a liquid substance with a contact angle of 10° or less with the polymer coating agent and a plasticizer is continuously sprayed onto a solid drug while simultaneously coating it with a powdered polymer coating agent. However, the method in Patent Document 1 requires special equipment that can introduce a fixed amount of powder into the manufacturing apparatus. Also, the method in Patent Document 1 is prone to granulation and is only applicable to large particles or tablets. On the other hand, as a dry method, Patent Document 2 describes a method in which a polymer is dry-applied to particles having a core and a wax layer covering it, followed by a layering step in which the particles are crushed. However, since many existing dry methods involve coating in powder form, the resulting film may lack density, potentially failing to achieve the desired function. Furthermore, when forming a dense film using conventional techniques, there is a problem in that the polymers used for coating are limited to those with low minimum film-forming temperatures. Patent No. 3417772Patent No. 6067154 This is a schematic diagram (cross-sectional end view) showing film-coated granules 100 according to one embodiment of the present invention.This is a schematic diagram (cross-sectional end view) showing a nucleus particle 10 according to one embodiment.This is a flowchart illustrating a method for manufacturing a nuclear particle 10 according to one embodiment of the present invention.This is a schematic diagram (cross-sectional end view) showing a nuclear particle 20 according to one embodiment.This is a flowchart illustrating a method for manufacturing a nuclear particle 20 according to one embodiment.This is a schematic diagram (cross-sectional end view) showing film-coated granules 200 according to one embodiment.(A) is a flowchart illustrating the process of preparing a porous material 150 on which a plasticizer has been adsorbed according to one embodiment, and (B) is a flowchart illustrating the method for manufacturing film-coated granules 100 according to one embodiment.(A) is a scanning electron microscope image of the particles of Example 1 before curing, (B) is a scanning electron microscope image of the particles of Example 1 after curing, (C) is a scanning electron microscope image of the particles of Example 2 before curing, and (D) is a scanning electron microscope image of the particles of Example 2 after curing.(A) is a scanning electron microscope image of the particles of Comparative Example 2 before curing, and (B) is a scanning electron microscope image of the particles of Comparative Example 2 after curing.This figure shows the dissolution rate of duloxetine hydrochloride in the film-coated granules of Example 3 and Comparative Example 4. The film-coated granules, formulations containing them, and methods for producing them according to the present invention will be described below with reference to the drawings. However, the film-coated granules, formulations containing them, and methods for producing them according to the present invention are not limited to the descriptions of the embodiments and examples shown below. In the drawings referenced in this embodiment and the examples described later, the same parts or parts having similar functions are denoted by the same reference numerals, and repeated descriptions thereof are omitted. As mentioned above, when using the dry process, the polymer is attached in powder form, resulting in lower film density. In the dry process, to create a dense film, it is necessary to soften the polymer by heating it to a temperature above its minimum film-forming temperature. However, considering the thermal stability of the active pharmaceutical ingredient and the heating limits of the manufacturing equipment, only polymers with low minimum film-forming temperatures can be used. Therefore, when using other polymers, it is necessary to lower the minimum film-forming temperature of the polymer. Fo