Method for the formation of low-substituted hydroxypropyl cellulose particles

#1. Field of the Invention

#This invention generally relates to a process for the production of low-substituted hydroxypropyl cellulose that is added for the purpose of imparting disintegration properties or binding properties during the manufacture of preparations in the fields of medicines, foods and the like. More particularly, it relates to a method for the formation of neutralization-precipitated particles of low-substituted hydroxypropyl cellulose in a purification step.

#2. Description of the Related Art

#Pulp was dipped in a 43 wt % solution of sodium hydroxide and then pressed to obtain an alkali cellulose composed of 22.2% by weight of NaOH, 44.8% by weight of cellulose, and 33.0% by weight of H2O. A reactor having a capacity of 5 liters was charged with 350 g (on a cellulose basis) of the alkali cellulose, and its atmosphere was replaced with nitrogen. After the addition of 79 g (0.226 part by weight per part by weight of cellulose) of propylene oxide, reaction was effected at a jacket temperature of 45° C. for 2 hours and 65° C. for 30 minutes. Thus, there was obtained 857 g of a crude hydroxypropyl cellulose product in which the number of moles of the hydroxypropoxyl substituted group per mole of the glucose unit was 0.25. While a double-shaft continuous kneader (KRC Kneader Model S2, manufactured by Kurimoto Tekkojo Co., Ltd.; with a paddle diameter of 50 mm, a barrel length of 660 mm, an L/D ratio of 13.2, and an internal volume of 1.2 liters) was operated at a rotational speed of 100 rpm, a residence time of 105 seconds, and a jacket temperature of 20° C., the above reaction product was fed thereto at a constant rate of 150 g per minute and thereby granulated to yield a granular material of the reaction product. This granular material of the reaction product was neutralized by placing 5,160 g (i.e., an amount equivalent to sodium hydroxide contained in the reaction product) of 5 wt % acetic acid in a 10-liter vessel, and adding the granular material thereto. The total amount of the granular material could be treated in 5.7 minutes. The result of a washing test carried out according to the testing procedure which will be described later, and the result of a loose apparent density measurement made by washing the resulting neutralization-precipitated product, drying it, reducing it to a powder, and measuring the loose apparent density of a powder sample deposited through a 200-mesh (75 μm) screen are shown in Table 1.

#While a double-shaft continuous kneader (KRC Kneader Model S2, manufactured by Kurimoto Tekkojo Co., Ltd.; with a paddle diameter of 50 mm, a barrel length of 660 mm, an L/D ratio of 13.2, and an internal volume of 1.2 liters) was operated at a rotational speed of 100 rpm, a residence time of 30 seconds, and a jacket temperature of 20° C. and with a paddle arrangement different from that used in Example 1, the same reaction product as used in Example 1 was fed thereto at a constant rate of 200 g per minute and thereby granulated to yield a granular material of the reaction product. This granular material of the reaction product was neutralized by placing 5,160 g (i.e., an amount equivalent to sodium hydroxide contained in the reaction product) of 5 wt % acetic acid in a 10-liter vessel, and adding the granular material thereto. The total amount of the granular material could be treated in 4.3 minutes. The result of a washing test carried out according to the testing procedure which will be described later, and the result of a loose apparent density measurement made by washing the resulting neutralization-precipitated product, drying it, reducing it to a powder, and measuring the loose apparent density of a powder sample deposited through a 200-mesh screen are shown in Table 1.

#While a double-shaft continuous kneader (KRC Kneader Model S2, manufactured by Kurimoto Tekkojo Co., Ltd.; with a paddle diameter of 50 mm, a barrel length of 660 mm, an L/D ratio of 13.2, and an internal volume of 1.2 liters) was operated at a rotational speed of 150 rpm, a residence time of 80 seconds, and a jacket temperature of 20° C. and with the same paddle arrangement as used in Example 1, the same reaction product as used in Example 1 was fed thereto at a constant rate of 150 g per minute and thereby granulated to yield a granular material of the reaction product. This granular material of the reaction product was neutralized by placing 5,160 g (i.e., an amount equivalent to sodium hydroxide contained in the reaction product) of 5 wt % acetic acid in a 10-liter vessel, and adding the granular material thereto. The total amount of the granular material could be treated in 5.7 minutes. The result of a washing test carried out according to the testing procedure which will be described later, and the result of a loose apparent density measurement made by washing the resulting neutralization-precipitated product, drying it, reducing it to a powder, and measuring the loose apparent density of a powder sample deposited through a 200-mesh screen are shown in Table 1.