RELATED APPLICATION

This application claims priority from Japanese Patent Application No. 2018-139354, filed Jul. 25, 2018, the disclosures of which is incorporated by reference herein in its entirety.

BACKGROUND OF THE INVENTION

The invention relates to a method for producing hypromellose acetate succinate.

Hypromellose acetate succinate (hereinafter also referred to as “HPMCAS”) is a polymer having a cellulose skeleton with ether structures formed by introduction of methyl groups (—CH3) and hydroxypropyl groups (—C3H6OH), and ester structures formed by introduction of acetyl groups (—COCH3) and succinyl groups (—COC2H4COOH).

HPMCAS is widely used, particularly in the pharmaceutical field such as a field of coating applications in which HPMCAS is used as an enteric polymer material, and a field of solid dispersions in which HPMCAS is used together with a poorly water-soluble drug. Accordingly, HPMCAS desirably contains minimum impurities so that it is important to efficiently remove reaction reagents, by-products and the like in a washing step in the method for producing the HPMCAS.

For example, JP 2015-512456A, which is a Japanese phase publication of WO 2013/148154A, proposes a method for precipitating an esterified cellulose ether from a reaction product mixture, the method comprising steps of: contacting the reaction product mixture with water, and subjecting the resulting mixture of the water and the reaction product mixture to shear force with a shear rate of at least 800 s−1.

SUMMARY OF THE INVENTION

However, the method disclosed in JP 2015-512456A requires installation of a high shear device, such as a rotor-stator mixer, a homogenizer, a high shear mill or a high shear pump, to obtain a high shear rate, leading to complication in the equipment. In addition, finely powdered cellulose ether particles exhibit poor filterability during washing so that impurities cannot be removed efficiently.

The invention has been made in these circumstances. An object of the invention is to provide a method for producing HPMCAS, the method not requiring any special device, and facilitating removal of impurities.

As a result of intensive researches to attain the object described above, the inventors have found that the filterability and washability of HPMCAS can be improved by neutralizing a suspension of HPMCAS with a basic substance in the method for producing the HPMCAS, and have completed the present invention.

In an aspect of the invention, there is provided a method for producing hypromellose acetate succinate, comprising an esterification step of esterifying hypromellose with an acetylating agent and a succinoylating agent in the presence of an aliphatic carboxylic acid to obtain a reaction product solution containing hypromellose acetate succinate; a precipitation step of precipitating the hypromellose acetate succinate by mixing the reaction product solution with water to obtain a suspension of the precipitated hypromellose acetate succinate; a neutralization step of neutralizing the suspension with a basic substance to obtain a neutralized suspension; and a washing step of washing the hypromellose acetate succinate contained in the neutralized suspension to obtain the washed hypromellose acetate succinate.

According to the invention, the filterability and washability of HPMCAS can be improved without any special equipment in the method for producing the HPMCAS so that the HPMCAS having impurities reduced can be conveniently produced.

