Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1994-06-24
1997-01-14
Spear, James M.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424464, 424480, 424482, A61K 922, A61K 932, A61K 936
Patent
active
055936946
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This is a 371 of PCT/JP92/01287 filed Oct. 5, 1992.
The present invention relates to an orally-administered sustained release tablet showing the zero order dissolution property to maintain a constant level of concentration of a drug in blood over a long period of time.
BACKGROUND ART
Many of the pharmaceutically active ingredients currently considered useful have a short biological half life and need to be administered several times a day. Should the administration frequency of such drugs can be decreased, it will not only lessen the burden on patients but also enhance compliance of the patients and bring about higher treatment effects. For this end, it is necessary to control release of a pharmaceutically active ingredient in such a manner that an effective concentration in blood can be maintained over an extended period of time.
In this regard, release of a drug at a constant rate (zero order dissolution) irrespective of the concentration of the drug which is in the dosage form as shown in FIG. 1a will be most ideal.
Such ideal zero order drug release maintains the concentration of a drug at a constant level in the tissues, thus allowing the drug concentration in blood to stay at a safe level. In particular, this release method is most effective for a drug which causes side effects even at a concentration a drug administration can easily achieve. In addition, the administration frequency can be decreased, since efficacy of the drug can be maintained for a long time. In contrast, a dissolution with decreasing rate with time, such as that shown in FIG. 1b and presently seen in many preparations, is called a first order dissolution.
Japanese Patent Unexamined Publication No. 23814/1988 reports a sustained release pharmaceutical composition for oral administration having almost zero order release property. According to this gazette, the composition has, in the main construction, a core material comprising at least a 20% derivative cellulose as a gelling agent, a drug homogeneously dispersed in the gelling agent and optionally a pharmaceutically acceptable excipient, and a coating of a permeable, slowly-dissolving derivative cellulose polymer applied to the core material. As the gelling agent, usable is, for example, hydroxypropylmethylcellulose and as the coating polymer, usable is, for example, a dispersion of ethylcellulose (aqueous dispersion). According to the examples therein, however, the zero order release continues for the first 10 hours or up to 85% dissolution at most, and it is not verified if the dissolution remains zero order up to 100%. The reason therefor is that the ethylcellulose for the coating layer has poor binding property when used as an aqueous dispersion and the core swells as the gellation proceeds, to the point that the coating layer is finally broken.
Besides the aforementioned, there are many controlled release (sustained release) preparations being studied, such as those shown in the following.
A sustained release preparation comprising rapidly dissolving granules and slowly released granules in combination in, for example, a capsule, such as the one for rhinitis achieves the sustained release according to a preparation design in which the rapidly dissolving part is dissolved immediately after administration and then a predetermined amount of a drug is released gradually from the slowly released part. In this case, the defect is that the production of the granules to be released slowly with time should be modified every time a drug to be contained changes, as can be seen in Japanese Patent Unexamined Publication Nos. 103012/1987, 197433/1989 and 230513/1989. The release of a drug from globular sustained release granules as described does not make a zero order release, since dissolution rate slows down with time due to the decreasing concentration gradient of the drug contained in the granules, as a result of the dissolution of the drug through an outer layer without destruction of the granules. This type of preparation mostly releases drug by allowing same to
REFERENCES:
patent: 4610870 (1986-09-01), Jain et al.
patent: 4871549 (1989-10-01), Ueda et al.
patent: 4919938 (1990-04-01), Lovegrove et al.
patent: 5279832 (1994-01-01), Greissinger et al.
The United States Pharmacopeia, 1995, USP 23, NF 18, Croscarmellose Sodium, p. 2238.
Hayashida Tomohiro
Kikumaru Kadoya
Tomoyuki Omura
Spear James M.
Yoshitomi Pharmaceutical Industries Ltd.
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