Pharmaceutical formulation as well as a process for its preparation

Claim 2

A pharmaceutical composition useful for the controlled release of a non-steroid anti-rheumatic, wherein said composition comprises a capsule containing the following first and second pellets, each of which contains a non-steroid anti-rheumatic: (i) first pellets in a form resistant to gastric juices, said first pellets comprising a two-layer membrane resistant to gastric juices comprising a primer coating membrane which has incorporated therein a water-insoluble organic acid and a main coating membrane, and (ii) second pellets in retard release form containing a retard permeable diffusion membrane, wherein the weight ratio of the first pellets resistant to gastric juices to the second pellets in retard release form is form 0.1:1 to 2:1.

Claim 3

The pharmaceutical composition as set forth in claim 1, wherein said primer coating membrane and said main coating membrane consist of a cellulose ester derivative, and wherein said retard permeable diffusion membrane comprises one or more acrylic resin layers.

Claim 4

The pharmaceutical composition as set forth in claim 1, wherein said capsule is a hard gelatin capsule.

Claim 5

The pharmaceutical composition as set forth in claim 1, wherein said non-steroid antirheumatic is a compound selected from the group consisting of acemetacine, diclofenac, fenoprofen, ibuprofen, indometacine, ketoprofen, mefen amino acid, naproxene, sulindac, tiaprofenic acid, tolmetine and a salt of said compounds.

Claim 6

The pharmaceutical composition as set forth in claim 1, wherein said non-steroid antirheumatic is disclofenac-sodium.

Claim 7

The pharmaceutical composition as set forth in claim 1, wherein said pellets contain from 10 to 95% by weight of said non-steroid antirheumatic.

Claim 8

The pharmaceutical composition as set forth in claim 1, wherein said pellets have an average diameter of from 0.4 to 2.0 mm and are encased by a membrane which has a thickness of from 0.001 to 0.5 mm.

Claim 9

The pharmaceutical composition as set forth in claim 1, wherein said capsule contains from 10 to 500 mg of said non-steroid antirheumatic.

Claim 10

The pharmaceutical composition as set forth in claim 1, wherein the membrane employed in said first pellets resistant to gastric juices is composed of two layers of cellulose ester with different substitution degrees, which are esterified with phthalic acid anhydride.

Claim 11

The pharmaceutical composition as set forth in claim 1, wherein the membrane employed in said first pellets resistant to gastric juices is composed of a primer coating membrane which comprises hydroxypropyl methyl cellulose phthalate and a water-insoluble organic acid, and a main coating membrane which comprises hydroxypropyl methyl cellulose phthalate.

Claim 12

The pharmaceutical composition as set forth in claim 1, wherein said organic acid is stearic acid.

Claim 13

The pharmaceutical composition as set forth in claim 2, wherein said acrylic resin layers of said retard release form are composed of an inner layer difficult to permeate and of an easily permeable outer layer.

Claim 14

The pharmaceutical composition as set forth in claim 2, wherein the acrylic resin of said retard release form is a polymerizate of acrylic and methacrylic acid ester containing a small amount of quaternary ammonium groups.

Claim 15

The pharmaceutical composition as set forth in claim 1, wherein the two-layer membrane resistant to gastric juices is composed as follows: Primer coating membrane: ______________________________________ hydroxypropyl methyl cellulose phthalate 50 g stearic acid 143 g talc 25 g ______________________________________ Main coating membrane: ______________________________________ hydroxypropyl methyl cellulose phthalate 100 g acetylated monoglyceride 10 g ______________________________________ and wherein the retard permeable diffusion membrane has two layers and is composed of: ______________________________________ a polymerizate of acrylic acid and methacrylic 20 g acid ester containing 5% of trimethyl ammonium methacrylate chloride a polymerizate of acrylic acid and methacrylic 10 g acid ester containing a small amount of quaternary ammonium groups talc 30 g phthalic acid dibutyl ester 3 g. ______________________________________