Method for manufacturing a pharmaceutical composition for controlled release of an active substance

Abstract

The present invention pertains to a sized product, which contains a drug, polyethylene oxide with a molecular weight of 2,000,000 or higher, and a specific size controlling agent for polyethylene oxide (substance with the appropriate plasticity and binding force) and wherein at least the above-mentioned specific size controlling agent is uniformly dispersed in the above-mentioned polyethylene oxide, a controlled-release pharmaceutical composition containing this sized product, and a method of manufacturing a controlled-release pharmaceutical composition containing this sized product.A controlled-release pharmaceutical composition with good uniformity of content can be presented by using powder particles of polyethylene oxide with powder properties suitable for tableting, which is obtained by uniform dispersion of the specific size controlling agent for polyethylene oxide of the present invention.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation application claiming priority to U.S. patent application Ser. No. 10 / 746,562 filed Dec. 23, 2003, allowed, which application claims the benefit of priority of U.S. Patent Application No. 60 / 453,046, filed Mar. 6, 2003, the disclosures of each application are hereby incorporated by reference in their entirety for all purposes.FIELD OF THE INVENTION[0002]The present invention pertains to a pharmaceutical composition for controlled release, which comprises a drug, polyethylene oxide with a molecular weight of 2,000,000 or higher, and a specific size controlling agent for the above-mentioned polyethylene oxide and wherein the above-mentioned drug and above-mentioned specific size controlling agent are uniformly dispersed in the above-mentioned polyethylene oxide. Moreover, the present invention pertains to a method of manufacturing this controlled-release pharmaceutical composition as well as a contro...

AI Technical Summary

Benefits of technology

[0020]Therefore, the present inventors discovered that when a portion of the polyethylene glycol (also PEG hereafter) that is used as a gelation enhancer (hydrophilic base) of the components of the above-mentioned hydrogel-forming sustained release pharmaceutical preparation is added to a suspension of the drug and this suspension is sprayed on the polyethylene oxide, polyethylene oxide with a high viscosity does not become thread-like and can be sized into powder that has properties (specific volume, and the like) suitable for tableting. Surprisingly, the inventors discovered that even if a suspension containing a low dose of the drug is sprayed, the controlled-release pharmaceutical preparation consisting of this spray-dried product is a pharmaceutical preparation with superior uniformity of content.

[0063]The “granulation” in the present Specification means a series of unit operations by which a granulated product of good uniformity is manufactured by binding particles to one another in order to improve adhesion and scattering of fine powder. In particular, when a pharmaceutical preparation with a low drug dose and good uniformity of content is to be manufactured, the drug is separately pulverized by itself, or pulverized after mixing with some of the additives to make fine particles in order to guarantee uniformity of content. Then a granulation process is generally conducted using a fluidized bed granulator. Consequently, growth of the particles is promoted by “granulation” and therefore, a powder with a large particle diameter and large specific volume is manufactured.

[0071]Tamsulosin and its pharmaceutically acceptable salts can be easily procured by the manufacturing method entered in Japanese Kokai Patents No. Sho 56-110665 and No. Sho 62-114952, or by manufacturing in accordance with this method.

[0102]Examples of the spraying device (method) are the high-shear agitation granulation method, crushing (pulverization) granulation method, fluidized bed granulation method, extrusion granulation method, tumbling granulation method, and spray granulation method, or device for by using its method thereof. The fluidized bed granulation method or device is preferred and the tumbling fluidized bed granulation or device is particularly preferred because it is possible to easily and uniformly mix a low-dose drug and hydrophilic base with PEO of a high viscosity.

[0129]Furthermore, although the examples of the present invention include an example in which the composition does not comprise a drug, this example is one where a very small dose of drug is used in the pharmaceutical preparation of the present invention, that is, a trace of drug (a trace dose that is effective in terms of treating or preventing disease) that is so small that it will not affect the properties of the PEO sized product is used in the pharmaceutical preparation of the present invention.

Problems solved by technology

The present inventors knew that many problems are encountered and realistically, manufacture is difficult during manufacturing a powder for controlled-release by aqueous system by using polyethylene oxide particles when the wet granulation method using a conventional binder is employed.

That is, for instance, a powder that is appropriate for tableting cannot be manufactured because various diverse problems are encountered.

For instance, when a binder that has binding force but shows poor plasticity, such as PVP, is used, granulation proceeds too far and powder particles with a high specific volume and poor fluidity are obtained, when a saccharide that has viscosity increasing power and binding force but becomes thread-like during spray drying, such as sorbitol, or a surfactant that has plasticity but shows poor binding force, such as polysorbate, is used, a powder with a small particle diameter is produced (the powder further breaks down into very fine particles) and becomes a powder that has a strong tendency toward being scattered and therefore, tableting is obstructed, and the like.

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