Manufacturing matrices

Details Manufacturing matrices Manufacturing matrices

1995-10-11

1998-09-08

Clardy, S. Mark

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Matrices

424464, 424468, 427 214, A61K 920

Patent

active

058042172

DESCRIPTION:

BRIEF SUMMARY
This application has been filed under 35 USC 371 as the national stage of international application PCT/SE94/00331, filed Apr. 14, 1994.


FIELD OF INVENTION

The present invention relates to a manufacturing process for multiple unit carriers and release controlling systems for bioactive substances from a wide variety of cellulose raw materials. It is also directed to the manufacture of additives to be used in tablet formation, especially in direct compression and to obtain multiple unit preparations in the form compressed and disintegrating tablets.


BACKGROUND OF THE INVENTION

The background of the present invention is previously disclosed in the international patent application WO 91/18590, published 12 Dec. 1991, which application also is referred to for a prior art review.
WO 91/18590 discloses a process for the manufacture of porous cellulose matrice particles, which have regular shape, and a capacity of sorbing 1.5-9 times of their own weight of water, a tap bulk density of less than 0.85 g/ml. The process for the manufacture of these porous cellulose matrices were performed by a mechanical treatment of hydrolyzed cellulose in a wet stage. The cellulose matrices preferably have a size of at least 0.1 mm and a tap bulk density of 0.1-0.7 g/ml.
According to this patent specification the bioactive substance or bioactive substances can be sorbed, precipitated or sublimized into the porous structure of the matrices. The matrices can also be admixed with bioactive substances or granules containing bioactive substances in order to improve the tabletting and tablet properties and thereafter compressed.
The manufacturing process according to this earlier patent application was found to give excellent results for wet hydrolyzed cellulose raw materials with suitable plastic properties. It was found possible to obtain reproducible properties of the porous matrices by controlling the hydrolysis and the mechanical treatment process. Commercial qualities of microcrystalline cellulose such as Avicel (FMC Corp), Emocel (Finn Sugar, Finland) and Dynacel (Cellupharm AB, Sweden) were found to give more dense particles, less suitable in many applications. Furthermore, it was found that the use of established microcrystalline cellulose qualities led to unacceptable differences in form, size and size distribution.
However, this manufacturing previously disclosed process is limited to wet celluloses subjected to chemical hydrolyzation, which is a disadvantageous restriction in the choice of raw materials. The use of wet hydrolysed cellulose is also connected with problems related to bacterial growth, especially in cases when the cellulose is not subjected to immediate processing. Furthermore, the hydrolysis process can be difficult to stop before it has reached the levelling off degree of polymerisation, at which stage the processed batch essentially contains microcrystalline cellulose. The process according to WO 91/18590 is preferably performed by a mechanical treatment followed by a forming step in a cyclone. Such a process is satisfying in a large-scale industrial context, but it will be less suitable for a production in a smaller scale. Therefore a demand exists for a process for preparation of the porous cellulose matrices in a smaller and more convenient units like high shear mixers.
In the former process disclosed in WO 91/18590 there is no method adviced for drying the cellulose particles. The drying shrinkage has been noticed as a problem when loading the matrice particles with an agent dissolved in a liquid, which does not re-expand the particles by swelling.
A problem related to the drying shrinkage is that a film coating on the matrice particle may burst when the particle re-expands in contact with an aqueous fluid.
It is the object of the present invention to provide a process which overcomes the above mentioned problems as well as satisfying the demand of being applicable on a wide variety of raw materials.


DESCRIPTION OF THE INVENTION

The present invention is directed to the process for the manufacture

REFERENCES:
patent: Re35460 (1997-02-01), Klungness et al.
patent: 3297806 (1967-01-01), Battista et al.
patent: 3873694 (1975-03-01), Kanig
patent: 4055510 (1977-10-01), Peska et al.
patent: 4090022 (1978-05-01), Tsao et al.
patent: 4138475 (1979-02-01), McAinsh et al.
patent: 4269859 (1981-05-01), Morse
patent: 4464224 (1984-08-01), Matolesy
patent: 4572833 (1986-02-01), Pedersen et al.
patent: 4606909 (1986-08-01), Bechgaard et al.
patent: 4775535 (1988-10-01), Lowey
patent: 4806360 (1989-02-01), Leong et al.
patent: 4808413 (1989-02-01), Joshi et al.
patent: 4855143 (1989-08-01), Lowey
patent: 4900558 (1990-02-01), Barry et al.
patent: 5049394 (1991-09-01), Howard et al.
patent: 5223090 (1993-06-01), Klungness et al.
patent: 5292461 (1994-03-01), Juch et al.
patent: 5302396 (1994-04-01), Phadke et al.
patent: 5508044 (1996-04-01), Buxton et al.
patent: 5601845 (1997-02-01), Buxton
patent: 5607695 (1997-03-01), Ek et al.
Yamauchi et al., Development of the Pore Structure of Paper Web during Consolidation, J. Japan Wood Res. Soc., Mokuzai Gakkaishi, vol. 25, No. 6, (1979), pp. 414-421.
British Pharmacopoeia, vol. 1, 1993, Cellulose, pp. 119-120.
English Abstract of Japanese 89-1272643 (Oct. 1989).
Bogentoft et al., Influence of Food on the Absorption of Acetylsalicylic Acid from Enteric-Coated Dosage Forms, Europ. J. Clin. Pharmacol. 24, 351-355 (1978), pp. 351-355.
Ragnarsson et al., Coated Drug Cores in Multiple Unit Preparations Influence of Particle Size, Drug Development and Industrial Pharmacy, 14(15-17), pp. 2285-2297 (1988).
Battista, Hydrolysis abnd Crystallization of Cellulose, Industrial and Engineering Chemistry, vol. 42(3), pp. 502-507. 1950.
Nystrom et al., Measurement of axial and radial tensile strength of tablets and their relation to capping, Acta Pharm. Suec. 15, pp. 226-232 (1978).

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