Excipient having high compactability and process for preparing same

• US 5,574,150 A
• Filed: 01/03/1994
• Issued: 11/12/1996
• Est. Priority Date: 01/05/1993
• Status: Expired due to Term

• Current Assignee: Asahi Kasei Kogyo Kabushiki Kaisha (Asahi Kasei Corporation)
• Original Assignee: Asahi Kasei Kogyo Kabushiki Kaisha (Asahi Kasei Corporation)
• Inventors: Miyamoto, Hiroto, Yaginuma, Yoshihito, Nagatomo, Sueo
• Primary Examiner(s): Mullis, Jeffrey C.
• Application Number:
  US08/176,623
• Time in Patent Office: 1,044 Days
• Field of Search: 536/56, 536/124
• US Class Current: 536/56
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: C08B 15/02 Oxycellulose; Hydrocellulose; Cellulosehydrate, e.g. microcrystalline cellulose

Abstract

Disclosed is an excipient comprising white powdery microcrystalline cellulose having an average degree of polymerization of from 100 to 375 and an acetic acid holding capacity of 280% or more, and having a specific compression characteristic satisfying an equality of formula (1): ##EQU1## wherein a is from 0.85 to 0.90, b is from 0.05 to 0.10, P represents the compression pressure (kgf/cm²) applied to the microcrystalline cellulose, V_o represents the apparent specific volume (cm³ /g) of the microcrystalline cellulose, and V_p represents the specific volume (cm³ /g) of the microcrystalline cellulose at the compression pressure P. The excipient of the present invention exhibits not only high compactability but also high rate of disintegration. The excipient of the present invention can be advantageously obtained by heat-treating an aqueous dispersion of purified cellulose particles, which has a solids content of 40% or less by weight, at 100° C. or more, followed by drying, or by subjecting an aqueous dispersion of purified cellulose particles having a solids content of 23% or less by weight to thin film-forming treatment and drying the resultant thin film.

Claims

1. An excipient having high compactability, comprising white powdery microcrystalline cellulose obtained by subjecting a cellulosic material to hydrolysis with acid or oxidative degradation with alkali, said microcrystalline cellulose having an average degree of polymerization of from 100 to 375 and an acetic acid holding capacity of 280% or more, and having a compression characteristic satisfying an equality of formula (1):

##EQU8## wherein a is from 0.85 to 0.90, b is from 0.05 to 0.10, P represents the compression pressure (kgf/cm²) applied to said microcrystalline cellulose, V_o represents the apparent specific volume (cm³ /g) of said microcrystalline cellulose, and V_p represents the specific volume (cm³ /g) of said microcrystalline cellulose at said compression pressure P,

wherein said white powdery microcrystalline cellulose has an apparent specific volume of from 4.0 to 6.0 cm³ /q, a tapping apparent specific volume of 2.4 cm³ /q or more and a specific surface area of less than 20 m² /g, and a content of particles having a diameter of 355 μ

m or more of 5% by weight or less, and has an average particle diameter of from 30 to 120 μ

m, and

wherein said white powdery microcrystalline cellulose is further characterized such that when 500 mg of said microcrystalline cellulose is compressed at 100 kqf/cm² for 10 seconds to form a cylindrical tablet having a circular cross-sectional area of 1 cm², said tablet has a breaking strength of 10 kqf or more in a diametric direction thereof, and exhibits a disintegration time of 100 seconds or less, and

wherein said acetic acid holding capacity means the amount of acetic acid which can be held by the pores of the powdery microcrystalline cellulose when the powdery microcrystalline cellulose is equilibrated with acetic acid, and is expressed in a weight percentage of the acetic acid which can be held by the microcrystalline cellulose, relative to the weight of the microcrystalline cellulose in a dry state, and wherein said tapping apparent specific volume is measured by a method in which a glass cylinder containing the white powdery microcrystalline cellulose lightly packed therein is subjected to tapping onto a stand made of a relatively soft material from a height of several centimeters in an approximately vertical direction until the packing density of the white powdery microcrystalline cellulose is not increased by tapping any more, and the volume of the resultant white powdery microcrystalline cellulose is measured and divided by the weight of the white powdery microcrystalline cellulose.

2. The excipient according to claim 1, wherein the average degree of polymerization of said white powdery microcrystalline cellulose is from 180 to 220.

3. The excipient according to claim 1, wherein said cylindrical tablet has a breaking strength of 11 kgf or more in a diametric direction thereof.

4. The excipient according to any one of claims 1, 2 and 3, wherein said microcrystalline cellulose is further characterized such that when said microcrystalline cellulose has a water content of from 5 to 6% by weight, the microcrystalline cellulose has a transverse relaxation time of 0.00024 second or less with respect to said water, as measured by NMR spectroscopic analysis.

5. A process for preparing the excipient according to claim 1, which comprises subjecting a cellulosic material to hydrolysis with acid, or oxidative degradation with alkali to form cellulose particles, subjecting said cellulose particles to purification to obtain aqueous purified cellulose particles, adjusting the water content of said aqueous purified cellulose particles to obtain an aqueous dispersion of the purified cellulose particles, wherein said aqueous dispersion has a solids content of 40% or less by weight, a pH value of from 5 to 8.5 and an electrical conductivity of 300 μ

s/cm or less, and subjecting said aqueous dispersion to heat treatment at 100°

C. or more, followed by drying, thereby obtaining a microcrystalline cellulose.

6. The process according to claim 5, wherein said aqueous dispersion of the purified cellulose particles has a solids content of from 5 to 23% by weight.

7. The process according to claim 5 or 6, wherein said heat treatment and said drying are performed by means of a drum dryer or a belt dryer.

8. The process according to claim 5 or 6, wherein said microcrystalline cellulose is subjected to pulverizing and sieving to adjust the particle size distribution thereof.

9. A process for preparing the excipient according to claim 1, which comprises subjecting a cellulosic material to hydrolysis with acid or oxidative degradation with alkali to form cellulose particles, subjecting said cellulose particles to purification to obtain aqueous purified cellulose particles, adjusting the water content of said aqueous purified cellulose particles to obtain an aqueous dispersion of the purified cellulose particles, wherein said aqueous dispersion has a solids content of 23% or less by weight, a pH value of from 5 to 8.5 and an electrical conductivity of 300 μ

s/cm or less, and spreading said aqueous dispersion on a substrate to obtain a film of said aqueous dispersion, followed by drying, thereby obtaining a microcrystalline cellulose.

10. The process according to claim 9, wherein said drying is performed by means of a drum dryer or a belt dryer.

11. The process according to claim 9, wherein said microcrystalline cellulose is subjected to pulverizing and sieving to adjust the particle size distribution thereof.