Claims
- 1. A controlled-release pharmaceutical dosage form comprising:
- a multiplicity of microgranules containing naproxen as an active ingredient and at least one excipient, said microgranules having substantially no controlled-release properties prior to coating,
- a series of successive polymeric coatings that coat said microgranules, comprising:
- a first coating applied directly to the microgranules, at least said first coating imparting controlled-release properties to said microgranules, said coating comprising polyethylene glycol as one ingredient thereof;
- a second coating with hydrophilic characteristics;
- a third applied coating with lipophilic characteristics; and
- an outermost coating with hydrophilic characteristics, at least said outermost coating imparting resistance of said microgranules to dissolution in gastric fluids;
- said microgranules after coating having sizes ranging from 50 to 500 .mu.m.
- 2. The dosage form of claim 1, wherein said microgranules, prior to coating, have a homogeneous and uniformly smooth surface, a substantially spherical shape, an apparent density of between 300 and 800 g/l, and a low friability.
- 3. The dosage form of claim 1 wherein said microgranules, prior to coating, contain more than 50% naproxen by weight.
- 4. The dosage form of claim 2, wherein said microgranules, after coating, have dimensions of between about 90 and about 300 .mu.m.
- 5. The dosage form of claim 1, wherein:
- the excipient is a member selected from the group consisting of polyvinylpyrrolidone, lactose and dibasic calcium phosphate;
- the first release-control imparting coating comprises a mixture of a cellulose derivative, a plasticizer, and polyethylene glycol;
- the second coating comprises a member selected from the group consisting of methyl cellulose, methacrylic acid copolymers, polyvinylpyrrolidone, and mixtures of at least two of the foregoing;
- the third coating comprises a member selected from the group consisting of mono-, di-, and triglycerides of fatty acids, waxes, fatty alcohols and fatty acids; and
- the outermost coating comprises a plasticizer and a member selected from the group consisting of polymers forming enteric coatings.
- 6. The dosage form of claim 1, wherein the first coating applied to said microgranules comprises diethyl phthalate in a range from about 10% to about 30% by weight compared to the weight of the total ingredients of the first coating mixture exclusive of solvents and further comprises polyethylene glycol in a range from about 0.1% to about 5% by weight compared to the total weight of the first coating mixture, exclusive of solvents.
- 7. The controlled release pharmaceutical dosage form of claim 1, wherein the second coating of hydrophilic material applied to the first coating comprises diethyl phthalate in a range from about 10% to about 30% by weight as compared to the total weight of the second coating mixture, exclusive of solvents.
- 8. The controlled release pharmaceutical dosage form of claim 5, wherein the outermost coating comprises cellulose acetate phthalate as the enteric coating forming polymer and, as the plasticizer, diethyl phthalate said diethyl phthalate being in an amount within the range from about 10% to about 30% by weight as compared to the total weight of the second coating mixture, exclusive of solvents.
- 9. A controlled release pharmaceutical dosage form comprising a liquid dosage formulation for immediate use said formulation containing the dosage form of claim 1 suspended in water.
- 10. A controlled release pharmaceutical dosage form comprising a liquid dosage formulation containing the dosage form of claim 1 suspended in a physiologically acceptable aqueous medium.
Priority Claims (1)
Number |
Date |
Country |
Kind |
M192A2826 |
Dec 1992 |
ITX |
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Parent Case Info
This application is a continuation-in-part of U.S. patent application Ser. No. 928,616 filed Aug. 10, 1992 (now U.S. Pat. No. 5,296,236) which is a continuation of Ser. No. 711,588, filed Jun. 6, 1991, in turn is a continuation of Ser. No. 408,755 filed Sep. 18, 1989 (both now abandoned).
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
3904682 |
Fried et al. |
Sep 1975 |
|
4009197 |
Fried et al. |
Feb 1977 |
|
4803079 |
Hsiao et al. |
Feb 1989 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
903540 |
Feb 1986 |
BEX |
308739 |
Sep 1988 |
EPX |
Continuations (2)
|
Number |
Date |
Country |
Parent |
711588 |
Jun 1991 |
|
Parent |
408755 |
Sep 1989 |
|
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
928616 |
Aug 1992 |
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