Monolithic tablet for controlled drug release

• US 6,090,411 A
• Filed: 03/09/1998
• Issued: 07/18/2000
• Est. Priority Date: 03/09/1998
• Status: Expired due to Term

• Current Assignee: Temple University of The Commonwealth System of Higher Education
• Original Assignee: Temple University
• Inventors: Pillay, Viness, Fassihi, Reza
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/037,096
• Time in Patent Office: 862 Days
• Field of Search: 424/486, 424/488, 424/466, 424/465, 424/468, 514/960
• US Class Current: 424/468
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

A swellable hydrophillic matrix tablet that delivers drugs in a controlled manner over a long period of time and is easy to manufacture. More specifically, the drug is disposed in a matrix composed of HPMC or polyethylene oxide, in the presence of a salt, which may be a combination of salts. Suitable salts include sodium bicarbonate, sodium chloride, potassium bicarbonate, calcium chloride, sodium bisulfate, sodium sulfite, and magnesium sulfate. Outward diffusion of the drug is controlled by an inwardly progressing hardening reaction between the salt and the dissolution medium, possibly also involving the drug itself.

Claims

1. A monolithic controlled release drug delivery tablet for improving linearity of drug delivery over a sustained period of time comprising a hydrophilic swellable polymeric matrix;

a pharmaceutically effective amount of an active agent whose degree of solubilization is substantially independent of pH over a pH in the range of pH 1.5 to pH 7 .5 dispersed in said matrix, and

an inorganic salt dispersed in said matrix at a concentration in the range of 50% to 100% by weight of the polymeric matrix, in which upon exposure to an aqueous medium, said salt causes a hardened boundary around the periphery of the matrix, said boundary sequentially progressing inwardly toward the center thereof as said aqueous medium permeates the matrix, said hardened boundary limiting the rate at which the pharmaceutically active agent in said matrix is released from the tablet,

with the proviso that said tablet does not include polyacrylic acid or its pharmaceutically acceptable salt and said tablet is a compressed blend of homogeneous powders comprising said polymeric matrix, said active agent, and said salt.

2. A monolithic controlled release drug delivery tablet for improving linearity of drug delivery over a sustained period of time as recited in claim 1 wherein said salt is selected from the group consisting of sodium chloride, sodium bicarbonate, potassium bicarbonate, sodium citrate, sodium bisulfate, sodium sulfite, magnesium sulfate, calcium chloride, potassium chloride, and sodium carbonate.

3. A monolithic controlled release drug delivery tablet for improving linearity delivery over a sustained period of time as recited in claim 1 wherein said hydrophilic swellable polymeric matrix is hydroxypropylmethylcellulose or polyethylene oxide.

4. A monolithic controlled release drug delivery tablet for improving linearity of drug delivery over a sustained period of time as recited in claim 1 wherein said pharmaceutically active agent is of high water solubility.

5. A monolithic controlled release drug delivery tablet for improving linearity of drug delivery over a sustained period of time as recited in claim 1 wherein said pharmaceutically active agent is of low water solubility.

6. A monolithic controlled release drug delivery tablet for improving linearity of drug delivery over a sustained period of time as recited in claim 1 wherein said pharmaceutically active agent is diltiazem, propranolol, or verapamil.

7. A monolithic controlled release drug delivery tablet for improving linearity of drug delivery over a sustained period of time consisting of:

a hydrophilic swellable polymeric matrix;

a pharmaceutically effective amount of an active agent dispersed in said matrix, said active agent having a degree of solubilization which is substantially independent of pH over a pH in the range of pH 1.5 to pH 7.5; and

a salt dispersed in said matrix at a concentration in the range of 50% to 100% by weight of the polymeric matrix, said salt being selected from one or two members of the group consisting of sodium chloride, sodium bicarbonate, potassium bicarbonate, sodium citrate, sodium bisulfate, sodium sulfite, magnesium sulfate, calcium chloride, potassium chloride, and sodium carbonate,

in which upon exposure to an aqueous medium, said salt causes a hardened boundary around the periphery of the matrix, said boundary sequentially progressing inwardly toward the center thereof as said aqueous medium permeates the matrix, said hardened boundary limiting the rate at which the pharmaceutically active agent in said matrix is released from the tablet,

with the proviso that said tablet is a compressed blend of homogeneous powders comprising said polymeric matrix, said active agent, and said salt.