JP2005160928A - Method for producing asymmetrical microcapsule having three-layer structure by jet blowout method and screen print method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for mass-producing an asymmetrical microcapsule being not more than 200 μm in size. <P>SOLUTION: A large amount of asymmetrical microcapsules are produced at low costs by the use of the methods by successively changing the amount of water insoluble polymer liquid, chemical liquid, and water soluble polymer liquid, while inserting a drying process, and discharging them onto a base board by trace amount, by performing printing on the base board by successively changing the amounts, while inserting the drying process, by the use of a screen printing mesh or by combining both the methods. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

The present invention provides a method capable of inexpensively mass-producing asymmetric microcapsules having a diameter of 500 μm or less in which microcapsules are provided with a plurality of functions (targetability, adhesion, release control, permeation promotion, etc.) in addition to release control. .

In Patent Documents 1 to 4 as manufacturing methods of asymmetric microcapsules, Takada invents the adhesion method, heat sealing method, ultrasonic sealing method, etc., but mass-produces asymmetrical microcapsules of 0.5 mm or less at low cost. Not suitable for.
Koji Takada, PCT / JP99 / 06602, An oral formulation for gastrointestinal drug delivery Koji Takada, Three-layered parenteral preparations. PCT / JP01 / 04355, Parenteral preparation with three-layer structure Koji Takada, small intestinal mucoadhesive patch Gastrointestinal mucoadhesive patch system (GI-MAPS) manufacturing method, Japanese Patent Application No. 2001-144002 Koji Takada, manufacturing method and apparatus for non-uniform millimeter and microcapsules, Japanese Patent Application 2003-153939

In order to mass-produce asymmetric microcapsules having a size of 0.5 mm or less at low cost, the drug layer must be wrapped with two different types of polymers. The conventional method of creating a recess in a film made of one polymer, inserting and injecting a drug, and then covering, sealing, and punching with the other polymer film cannot be mass-produced at low cost.

According to the present invention, the above problem can be solved by the following. That is, one polymer solution is first discharged onto a substrate such as a glass plate or a Teflon (registered trademark) plate by a blowing method such as inkjet. After drying or nearly drying, the liquid containing the drug is discharged onto the first polymer layer so as to have a smaller diameter. After drying or substantially drying, the other polymer solution is discharged with a diameter that is slightly larger than the drug layer. Finally, it is dried and peeled off from the substrate to obtain asymmetric microcapsules.
This problem can also be solved by using a screen printing method. That is, one polymer liquid is first printed on a substrate such as a glass plate by a screen printing method. After drying or nearly drying, the liquid containing the drug is printed on the first polymer layer so as to have a smaller diameter. After drying or almost drying, the other polymer solution is printed with a diameter larger than that of the drug layer. Finally, it is dried and peeled off from the substrate to obtain asymmetric microcapsules.
Furthermore, asymmetric microcapsules can be mass-produced at low cost by appropriately combining the above-described ejection method and printing method.

Thus, the method of mass-producing asymmetric microcapsules was invented by applying the microfabrication technology.

As the water-insoluble polymer solution, for example, an aqueous coating polymer solution such as Eudragit NE30D may be used. In addition, a solution obtained by dissolving a water-insoluble polymer such as ethyl cellulose or cellulose acetate using ethanol, methylene chloride, or a mixed solution thereof can also be used. As the chemical solution, in the case of a water-soluble drug, an aqueous solution or a solution prepared using a drug and an adhesive polymer such as methylcellulose using an appropriate solvent can be used. In the case of a fat-soluble drug, a suspended aqueous solution or a solution dissolved using an appropriate solvent can be used. In addition, oils and fats, a solution to which a surfactant is added, or a solvent in which a drug and an adhesive polymer are dispersed can also be used. As the water-soluble polymer solution, for example, an aqueous coating solution such as Eudragit L30D-55, hydroxypropylmethylcellulose acetate succinate (Aqoat, Acoat, Shin-Etsu Chemical) can be used. Alternatively, a solution obtained by dissolving an enteric polymer such as hydroxymethylcellulose phthalate, Eudragit L100, Eudragit S100, etc. using ethanol, methylene chloride or a mixture thereof can also be used.

As a water-insoluble polymer solution, 4 g of cellulose acetate, 2 g of hydroxypropylmethylcellulose phthalate (HP55 ^™ ), and 1.7 ml of triethyl citrate are added with 32 ml of acetone to obtain a dope solution. As a water-soluble polymer solution, HP55 ^™ 12.5 g, triethyl citrate 1.7 ml and acetone 37 ml are added and shaken well to obtain a dope solution. The chemical solution is prepared by dispersing 1 g of sodium cromoglycate and 100 mg of carboxymethyl cellulose in a 20% ethanol solution. First, a water-insoluble polymer liquid is printed on a glass plate using a screen having pores with a diameter of 150 μm. In the almost dry state, the chemical solution is then printed on the glass plate using a screen having pores with a diameter of 100 μm. Similarly, after becoming almost dry, a water-soluble polymer liquid is printed using a screen having pores with a diameter of 150 μm so as to wrap the almost dry chemical liquid layer. After drying well, it is peeled off from the glass plate to obtain asymmetric microcapsules.

A film is formed by widely applying a non-aqueous coating liquid Eudragit NE30D (Rohm Pharm) on a glass plate. A mixture of tranilast and methylcellulose is continuously ejected onto the water-insoluble polymer film at regular intervals using an inkjet printer head. After drying, a water-soluble film is formed by spraying Eudragit L30D-55, which is an aqueous coating solution. Individual microcapsules are formed by irradiating with a laser beam. Finally, it is peeled off from the substrate and sizing is performed to obtain asymmetric microcapsules.

A non-aqueous coating liquid Eudragit NE30D (manufactured by Rohm Pharm) and Eudragit L30D-55, which is an aqueous coating liquid, are widely applied on a glass plate to form two types of films. A mixed solution of tranilast and methylcellulose is continuously ejected onto the water-insoluble polymer film at regular intervals by a screen printing method. After drying, cover with an aqueous coating film. Individual microcapsules are formed by irradiating with a laser beam. Finally, it is peeled off from the substrate and sizing is performed to obtain asymmetric microcapsules.

A non-aqueous coating liquid Eudragit NE30D (Rohm Pharm) is ejected onto a glass plate in a size of about 150 μm in diameter by an ink jet printer method. After being almost dry, a mixture of hydrocortisone and Hibiswako 103 (Wako Pure Chemical Industries) is discharged in a size of about 120 μm in diameter. After almost drying, Eudragit L30D-55, which is an aqueous coating solution, is discharged in a size of about 150 μm in diameter. Finally, it is peeled off from the substrate and sizing is performed to obtain asymmetric microcapsules.

Develop highly functional preparations such as mucoadhesive sustained-release eye drops and nasal drops, skin-adhesive sustained-release mosquito repellent, cancer tissue targeting and sustained-release preparations, and inflammatory tissue-adhesive sustained-release preparations For this purpose, microcapsules having a plurality of functions such as target property, adhesion property, sustained release property and permeation promoting property are required. For this purpose, unlike conventional microcapsules, a method for producing asymmetric microcapsules must be devised. It is difficult to mass-produce asymmetric microcapsules having a size of 200 μm or less even when a manufacturing method of asymmetric microcapsules having a diameter of 500 μm or more is applied. Therefore, a method for mass-producing asymmetric microcapsules having a size of 200 μm or less was established by applying a micro discharge technology such as inkjet or a screen printing technology. Applications include mass production of asymmetric microcapsules with a size of 200 μm or less, mucoadhesive sustained-release eye drops / nasal drops, skin-adhesive sustained-release mosquito repellent, cancer tissue targeting adherent sustained-release Mass production of high-functional preparations such as adhesive preparations and sustained release preparations adhering to inflammatory tissues.

Claims (5)

A method for producing an asymmetric microcapsule having a three-layer structure by sequentially blowing a water-insoluble polymer solution, a drug, and a water-soluble polymer solution by a blowing method such as inkjet. A method of producing an asymmetric microcapsule having a three-layer structure after sequentially blowing out a water-insoluble polymer solution, a drug, and a water-soluble polymer solution by a blowing method such as ink jet and performing a peripheral treatment with a laser beam. A method for producing an asymmetric microcapsule having a three-layer structure by sequentially superposing and printing a water-insoluble polymer liquid, a drug, and a water-soluble polymer liquid by a screen printing method. A method of producing an asymmetric microcapsule having a three-layer structure after sequentially printing a water-insoluble polymer solution, a drug, and a water-soluble polymer solution by screen printing, performing peripheral treatment with laser light. A method for producing an asymmetric microcapsule having a three-layer structure by sequentially discharging and printing a water-insoluble polymer solution, a drug, and a water-soluble polymer solution by combining a blowing method such as inkjet and a screen printing method.