Sustained release matrix

• US 4,968,508 A
• Filed: 01/19/1989
• Issued: 11/06/1990
• Est. Priority Date: 02/27/1987
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Oren, Peter L., Seidler, Werner M. K.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US07/300,457
• Time in Patent Office: 656 Days
• Field of Search: 424/484, 424/465, 424/468, 424/470, 424/469, 424/480, 424/479, 424/482, 424/473
• US Class Current: 424/468
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Abstract

This invention provides a matrix composition for sustained drug delivery which is comprised of an active agent, a hydrophilic polymer and an enteric polymer. The enteric polymer is impermeable to gastric fluids and aids in retarding drug release in regions of low pH, thus allowing lower levels of hydrophilic polymer to be employed. At the pH range of intestinal fluids, this polymer will dissolve and thereby increase the permeability of the dosage form. This approach is useful in sustaining the release of numerous active agents whose solubility declines as the pH is increased, a characteristic of weakly basic drugs. By responding to changes in physiological pH, these sustained release dosage forms have acceptable performance, in spite of variability in the gastrointestinal transit times of the formulation.

Claims

1. A sustained release matrix formulation in tablet unit dosage from comprising from about 0.1% by weight to about 90% by weight of cefaclor, from about 5% by weight to about 29% by weight of a hydrophilic polymer, and from about 0.5% by weight to about 25% by weight of an acrylic polymer which dissolves at a pH in the range of about 5.0 to about 7.4, with the proviso that the total weight of the hydrophilic polymer and said acrylic polymer is less than 30% by weight of the formulation.

2. A formulation of claim 1 wherein the cefaclor is present at a concentration in the range of about 45% by weight to about 85% by weight.

3. A formulation of claim 1 wherein the hydrophilic polymer is present at a concentration in the range of about 5% by weight to about 20% by weight.

4. A formulation of claim 1 wherein the acrylic polymer is present at a concentration in the range of about 1.5% by weight to about 15% by weight.

5. The formulation of claim 1 which consists essentially of the following ingredients, in percent by weight:

space="preserve" listing-type="tabular">______________________________________ Weight Ingredient (Percent) ______________________________________ Cefaclor 75.80 mannitol 5.80 hydroxypropyl methylcellulose 14.93 methacrylic acid copolymer 1.09 hydroxypropyl cellulose 0.94 stearic acid powder 1.01 magnesium stearate 0.43 ______________________________________