US 2011 OO64805A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0064805 A1 Obae et al. (43) Pub. Date: Mar. 17, 2011 (54) POROUS CELLULOSE AGGREGATE AND Publication Classification MOLDING COMPOSITION THEREOF (51) Int. Cl. (75) Inventors: Kazuhiro Obae, Tokyo (JP); A69/20 (2006.01) HidekiO O Amakawa, Tokyo (JP); A6IR 9/16 (2006.01) Ichirochiro Ibuki,Ibuki.T Tokyo (JP)JP A6II 3/663/167 (2006.01) (73) Assignee: ASAHIKASE CHEMICALS A63L/92A6II 3/34 308:2006.O1 CORPORATION, Tokyo (JP) CI3K L/02 (2006.01) 21) Appl. No.: 12A926,318 (52) U.S. Cl. ......... 424/464; 424/499; 514/630; 514/622: (21) Appl. No 9 514/474; 514/570; 127/34; 127/37 (22) Filed: Nov. 9, 2010 (57) ABSTRACT Related U.S. Application Data A porous cellulose aggregate characterized by having a sec - - - ondary aggregate structure resulting from aggregation of pri (62) Division of application No. 11/918,979, filed on Oct. mary cellulose particles, having a pore Volume within a par 22, 2007, filed as application No. PCT/JP2006/308414 ticle of 0.265 to 2.625 cm/g, containing I-type crystals and on Apr. 21, 2006. having an average particle size of over 30 to 250 Lim, a specific surface area of 0.1 to less than 20 m/g, a repose angle of 25° (30) Foreign Application Priority Data to less than 44° and a swelling degree of 5% or more, and characterized by having the property of disintegrating in Apr. 22, 2005 (JP) ................................. 2005-124477 Water. Patent Application Publication Mar. 17, 2011 Sheet 1 of 4 US 2011/00648.05 A1 FIG.1 O 9.00 0.01 0.1 10 OO PORE DIAMETER (lum) FIG.2 O 0.001 0.01 0.1 0 OO PORE DIAMETER (lum) Patent Application Publication Mar. 17, 2011 Sheet 2 of 4 US 2011/0064805 A1 Patent Application Publication Mar. 17, 2011 Sheet 3 of 4 US 2011/0064805 A1 Patent Application Publication Mar. 17, 2011 Sheet 4 of 4 US 2011/0064805 A1 US 2011/00648.05 A1 Mar. 17, 2011 POROUS CELLULOSEAGGREGATE AND erty have a high disintegration property, and we realized that MOLDING COMPOSITION THEREOF for conventional cellulose powder, if the swelling property is high, the compactability is not sufficient, and conversely if the TECHNICAL FIELD compactability is high, the Swelling property is low. That is, 0001. The present invention relates to a porous cellulose no cellulose powder having both a high compactability and aggregate that is useful mainly as an excipient in the field of high swelling property has been known. We searched for a chemical engineering, in particular, of pharmaceuticals and method to make the particles porous while keeping the pore of foods, and a compacting (molding) composition thereof. diameter of porous cellulose particles as large as possible and have managed to solve the aforementioned problem. That is, we found that excess aggregation can be controlled, and the BACKGROUND ART inside of the particles can be made porous while keeping the 0002. In the fields of pharmaceuticals, foods and other pore diameter large by using primary cellulose particles hav chemical engineering and the like, it has been a general prac ing a specified range of average width and average thickness tice conventionally to prepare a molded body containing an and giving self-aggregation ability thereto. For the porous active ingredient using cellulose particles such as crystalline cellulose aggregates of Patent Document 1, it is described that cellulose, cellulose powder and the like as an excipient, and when two or more groups of cellulose particles having differ for these cellulose particles, good compactability, fluidity and ent particle size are mixed, and the cellulose dispersion is disintegration property are required. dried, the dispersed cellulose particles having a small average 0003 Patent Document 1 describes a porous cellulose particles size enter between the dispersed cellulose particle aggregate (corresponding to Comparative Example 15-17) components having a large average particle size, and for this having a secondary aggregate structure formed by aggrega reason an excess aggregation of the dispersed cellulose par tion of primary cellulose particles, the aggregate having a ticles having the larger average particle size is inhibited, and pore volume within a particle of 0.265 cm/g to 2.625 cm/g, a large pore Volume is created in the secondary aggregate containing type I crystals, and having an average particle size structure. However, since tight aggregation is formed among of more than 30 um and 250 Lim or less, a specific Surface area two or more groups of cellulose having different average of 1.3-20m/g, a repose angle of 25° or more andless than 44° particle size, the pore diameter of the porous cellulose aggre and properties to disintegrate in water, and a method for gates obtained by the method particularly disclosed in the producing the aforementioned porous cellulose aggregate Example was measured to be small, about 1.5um. Since the comprising a step of drying a dispersion containing two or porous cellulose aggregate of the present invention uses the more groups of primary cellulose particles having a different single primary cellulose particles, they are not aggregated as average particle size and a liquid medium wherein the cellu tightly as the porous cellulose aggregate of the Patent Docu lose dispersion particles have an average particle size of 1 to ment and they are different in having a minimum 3 um pore 110 um. Since the aforementioned porous cellulose aggregate diameter. For the size of pore diameter, the Patent Document of the Patent Document requires two or more groups of pri describes that a clear peak can be recognized in the range of mary cellulose particles having a different average particle 0.1-10 Lum and the median pore diameter, which is a peak top size, different primary cellulose particles prepared by two of the pore distribution and closely related to water perme processes such as grinding dried acid insoluble residue of ability into the particles, is preferably 0.3 um or larger, and commercially available pulp and the like have to be mixed as that although a larger median pore diameter is better, it is at described in Example of the Patent Document. On the other most 5 um considering its distribution. It is described that hand the porous cellulose particles of the present invention with a larger median pore diameter, there is better disintegra can be obtained advantageously with a single process without tion property, but it is speculated that in practice it is difficult going through a process of grinding or the like. The porous to obtain a large median pore diameter of 3 um or larger by the cellulose aggregates of the present invention can be obtained production method according to the Patent Document. The by a single process by making the primary cellulose particles porous cellulose aggregates of the present invention has an to have a specified range of average width and average thick advantage that porous cellulose aggregates having a large ness and by making flexible, thereby promoting entanglement median pore diameter of 3 um or above, which can not be of primary cellulose particles without being limited by the obtained by the production method of the Patent Document, major axis of the primary cellulose particles, in other words can be prepared by a single step without requiring mixing of by giving self aggregation ability thereto, and are clearly the different primary cellulose particles prepared through two different from that described in the Patent Document interms steps. of the production method. In addition, because the pore size 0004 Patent Document 2 describes porous cellulose par of the secondary aggregate structure of the porous cellulose ticles (corresponding to Comparative 6 of the present appli particles according to the Patent Document is Smaller than cation) having a crystal structure type I, having pores of that of the porous cellulose aggregates of the present inven diameter of 0.1 umor above and a porous rate of 20% or above tion, and the Swelling degree is lower in water, the disintegra and containing 90% by weight or above of a fraction with 350 tion property is sometimes not sufficient for making tablets mesh and above, which is obtained by mixing cellulose par for a formulation that severely requires disintegration prop ticles with the third component such as a crystalline com erty in the case of drugs which is insoluble in water, and even pound or the like that is insoluble or hard to be soluble in in the case of soluble drugs, when a water repellent additives water but soluble in an organic solvent, by granulating and Such as magnesium Stearate and the like has to be added to drying the mixture using water or a water Soluble organic avoid problems in tablet pressing Such as sticking and the like. Solvent and then extracting/removing the third component We have investigated in detail the particle structure which with an organic solvent. The porous cellulose particles controls disintegration property, and as a result confirmed described in this document is entirely different from the again that the cellulose particles having a high Swelling prop porous cellulose aggregates of the present invention in the US 2011/00648.05 A1 Mar. 17, 2011 particle structure, because the primary cellulose particles volume of 2.0-2.9 cm/g, the fluidity and disintegration prop form Such a homogeneous continuous film-like tight strong erty were good but the compactability was unsatisfactory, cellulose wall structure that the boundaries of the particles while with larger apparent specific volume of 3.0-3.2 cm/g, become unclear.