Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1993-12-30
1996-02-13
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424465, 424480, 514770, 5147723, 514784, 514824, 514960, 514961, A61K 920, A61K 936
Patent
active
054909872
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention provides a novel formulation of matter and a novel process for making it. In particular, the present invention provides unique and novel high potency (e.g. 1000 mg) tablets of colestipol hydrochloride having the advantageous properties of hardness, friability and thickness, and a novel process for making such tablets.
Colestipol is a basic anion exchange resin described as a high molecular weight copolymer of diethylenetriamine and 1-chloro-2,3-epoxypropane (hydrochloride), with approximately 1 out of 5 amine nitrogens protonated. It may also be named as diethylenetriamine-epichlorohydrin copolymer, hydrochloride. It is a light yellow resin which is hygroscopic and swells when placed in water or aqueous fluids. See Merck Index (Tenth Edition) #2440, page 2438. Colestipol hydrochloride is commercially available in granule form as COLESTID.RTM. Granules. See Physicians Desk Reference (PDR) 42nd Ed., p. 2119 (1988).
COLESTID.RTM. Granules are marketed as a hyperlipidemia agent for oral use. COLESTID.RTM. Granules are tasteless and odorless, although they may have a pronounced gritty texture when suspended in liquids consumed orally.
Cholesterol is the major, and probably the sole precursor of bile acids. During normal digestion, bile acids are secreted via the bile from the liver and gall bladder into the intestines. Bile acids emulsify the fat and lipid materials present in food, thus facilitating absorption. A major portion of the bile acids secreted is reabsorbed from the intestines and returned via the portal circulation to the liver, thus completing an enterohepatic cycle. Only very small amounts of bile acids are found in normal serum. Physicians' Desk Reference (P.D.R.) 42nd Edition, 1988, page 2115.
Colestipol hydrochloride, sold, e.g., in COLESTID.RTM. Granules, is indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low density lipoproteins). These granules must be consumed orally and typically require admixture with a pleasant tasting vehicle at the time of oral consumption. The typical daily dose of COLESTID.RTM. Granules employed for anti-hypercholesterolemia varies from 15 to 30 grams per day. Patients taking this medication ordinarily must continue to take anti-cholesterolemic drugs throughout their lives to maintain reduced serum cholesterol levels.
However, COLESTID.RTM. Granules, are not well tolerated by patients since the gritty texture of the product is objectionable, severely compromising the pharmaceutical elegance and patient acceptance. Further, the use of a granule formulation means that drug must be mixed with a liquid vehicle at the time of consumption, an inconvenience for many patients. For example, in order to take this drug, patients must measure the powder, disperse it in a liquid vehicle and drink the entire contents. Therefore, a pharmaceutically more elegant and convenient dosage form of Colestipol hydrochloride is needed, such as a tablet.
INFORMATION DISCLOSURE
U.S. patent application Ser. No. 07/623,904, filed Dec. 19, 1990, now abandoned (which is also International Publication No. WO 89/12452, published 28 Dec. 1989) discloses fine-milled colestipol hydrochloride and tablets made therefrom. Some of the differences between these tablets and the tablets of the current invention are listed in Table 1. Table 2 shows some of the differences between the processes used to make these two different tablets.
According to Table 1, the tablets of the present invention are much harder than the prior art tablets, yet they disintegrate readily. Also, the tablets of the present invention are advantageously smaller than the prior art tablets. Other advantageous properties of the tablets of the present invention, such as friability and disintegration time, are also set forth in the Table.
According to Table 2, the process of the present invention utilizes a wet granulation method at the bulk drug stage rather than direct compression, thus avoid
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"Pharmaceutical Dosage Forms": Tablets, vol. 1, Edited by H. A. Lieberman and L. Lachman, Marcel Dekker, Inc., New York and Basel, pp. 114-116, 122-129 and 184-185, (1980).
USP XXII "Povidone", p. 1118, (1990).
"Remington's Pharmaceutical Sciences", RPS XIV, John E. Hoover, Managing Editor, 14th Edition, Mack Publishing Co. Pa., pp. 1655-1659, (1970).
Physicians' Desk Reference (PDR), 42nd Edition, 1988, p. 2115.
Price Jeffrey E.
Shen Robert W.
Gammill Martha A.
Page Thurman K.
Spear James M.
The Upjohn Company
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