KR-102960756-B1 - HYDROXYPROPYL METHYL CELLULOSE PHTHALATE AND METHOD FOR PRODUCING THE SAME

Abstract

The present invention provides a method for manufacturing HPMCP comprising at least: an esterification reaction process in which a reaction solution containing HPMCP is obtained by performing an esterification reaction between hydroxypropylmethylcellulose and a carboxybenzoylating agent in the presence of an aliphatic carboxylic acid in a kneader reactor equipped with a plurality of stirring blades that rotate and revolve; a precipitation process in which a suspension of precipitated HPMCP is obtained by mixing the reaction solution with water; and a washing and recovery process in which HPMCP in the suspension is washed and the washed HPMCP is recovered. Furthermore, the present invention provides HPMCP in which the yellowness of a solution containing 10 mass% of HPMCP in an acetone solvent is 10.0 or less at 20°C.

Inventors

• 기타구치, 다이시
• 마츠바라, 준이치
• 요시다, 미츠히로

Assignees

• 신에쓰 가가꾸 고교 가부시끼가이샤

Dates

Publication Date

20260507

Application Date

20201028

Priority Date

20191101

Claims (3)

1. An esterification reaction process for obtaining a reaction solution containing hydroxypropylmethylcellulose phthalate by performing an esterification reaction between hydroxypropylmethylcellulose and a carboxybenzoylating agent in the presence of an aliphatic carboxylic acid in a kneader reactor equipped with a plurality of stirring blades that rotate and revolve, and A precipitation process for obtaining a suspension in which the hydroxypropylmethylcellulose phthalate is precipitated by mixing the above reaction solution with water, and A washing and recovery process for washing hydroxypropylmethylcellulose phthalate in the above suspension and recovering the washed hydroxypropylmethylcellulose phthalate. A method for manufacturing hydroxypropylmethylcellulose phthalate comprising at least [the following].
2. A method for manufacturing hydroxypropylmethylcellulose phthalate according to claim 1, wherein the shape of the stirring blade is selected from the group consisting of a frame-shaped, turbine-shaped, ribbon-shaped, and anchor-wing-shaped.
3. delete

Description

Hydroxypropylmethylcellulose phthalate and method for producing the same The present invention relates to hydroxypropylmethylcellulose phthalate and a method for manufacturing the same. Hydroxypropylmethylcellulose phthalate (also known as hypromellose phthalate, hereinafter referred to as "HPMCP"), one of the enteric agents, is widely used for applications such as preparing solid dispersions by hot melt extrusion or spray drying methods in combination with water-insoluble drugs, and for coating applications aimed at controlling drug release. In particular, enteric-coated formulations are one of the important formulations widely used for purposes such as administering drugs unstable to acid or protecting the gastric mucosa. In the manufacture of enteric-coated formulations, a method is generally used in which HPMCP is dissolved in an organic solvent and sprayed to form an enteric film on the surface of the drug-containing formulation. Since this coating is applied to the outermost surface of the formulation, it is desirable that the discoloration of the HPMCP used for the coating be as minimal as possible, considering the ease of discoloration during formulation and the visual sensation during administration. Esterified cellulose ethers, such as HPMCP, can be prepared by known methods. For example, with respect to water-soluble cellulose ethers, esterified cellulose ethers can be prepared by a method in which an aliphatic carboxylic acid is used as a solvent, an alkali metal salt as a catalyst, and an acid anhydride as an esterifying agent, and the reaction is carried out using a twin-axis kneader (Japanese Patent Publication No. Hei 8-333401). As a stirring device, a planetary mixer in which a rotation axis is connected to an orbital axis and a stirring blade performs orbital and rotational motions simultaneously within the tank is used in the manufacture of a liquid developer (see FIGS. 1 to 3 of International Publication No. 2018/116658). Figure 1 is a conceptual cross-sectional view of a kneader reactor equipped with three stirring blades. Figure 2 shows a stirring blade connected to a kneader reactor. FIG. 3 shows examples of stirring blades having frame shapes of (a) a square, (b) a pentagon, and (c) a twisted square. Figure 4 shows examples of stirring blades, (a) turbine-shaped, (b) ribbon-shaped, and (c) anchor-wing-shaped. In the esterification reaction process, a reaction solution containing hydroxypropylmethylcellulose phthalate is obtained by carrying out an esterification reaction between hydroxypropylmethylcellulose and a carboxybenzoylating agent in the presence of an aliphatic carboxylic acid in a kneader reactor equipped with a plurality of stirring blades that rotate and revolve simultaneously. A kneader reactor is equipped with a plurality of stirring blades that rotate and revolve, a rotating part for performing rotational motion, a rotating part for performing revolvement, and a reaction vessel. The rotating part for performing rotational motion is positioned on the rotating part for performing revolvement. Since the kneader reactor enables stirring by revolvement in addition to stirring by rotational motion—that is, stirring by planetary motion—it is possible to perform the esterification reaction while applying sufficient shear force to the reaction solution of HPMCP. From the perspective of applying sufficient shear force to the reaction solution of HPMCP, it is preferable that the rotational directions of rotational motion and revolvement are opposite. For example, FIG. 1 illustrates a case in which three stirring blades are provided for orbiting while rotating. FIG. 1 is a conceptual cross-sectional view of a kneader reactor (1) provided with three stirring blades. The rotation axis and the orbit axis of the stirring blades are arranged parallel to each other in the vertical direction. Arrows indicate the direction of rotation of orbit or rotation. The rotation axis (7) of the stirring blades forming the rotational orbit (6) of the stirring blades is arranged to be the vertex of an equilateral triangle with the center (5) of the rotating part (4) for orbiting motion as the center of gravity. In this way, when providing three or more stirring blades that rotate while orbiting, it is preferable that the rotation axis of the stirring blades be arranged to be the vertex of a regular polygon with the center of gravity of the rotating part for orbiting motion as the center of gravity relative to the rotating part for orbiting motion. Likewise, in the case of having two stirring blades that rotate and revolve, it is preferable that the axis of rotation of the stirring blade be positioned such that it becomes the two ends of a straight line with the center of gravity at the center of the rotating part for performing the revolvement motion. In a kneader reactor, the rotation axis and rotation axis of the stirring blade are positioned so that they are perpendicular to the surface of the ear