Pharmaceutical composition

A method of treating moderate to severe pain in a human, the method comprising:

• the human orally taking an intact composition in an amount sufficient to treat the moderate to severe pain,
• wherein the composition comprises a plurality of multi-layer pellets comprising:
• a. a water-soluble core;
• b. an antagonist containing layer comprising naltrexone HCl coating the core;
• c. a sequestering polymer layer coating the antagonist containing layer;
• d. an agonist layer comprising morphine sulfate coating the sequestering polymer layer;
• e. a controlled release layer coating the agonist layer;
• and
• f. immediately beneath the agonist layer, an osmotic pressure regulating agent layer comprising sodium chloride;
• wherein the sequestering polymer layer comprises copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups, sodium lauryl sulfate in an amount from 1.6% to 6.3% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis, and talc in an amount of from 75% to 125% of the copolymers of acrylic and methacrylic acid esters with quaternary ammonium groups on a weight-to-weight basis;
• wherein the agonist layer comprises morphine sulfate and hydroxypropyl cellulose;
• wherein in the multi-layer pellets, the sodium lauryl sulfate is only contained in the sequestering polymer layer;
• and
• wherein the composition sequesters at least 80% of the naltrexone HCl as determined at 73 hours by first placing the composition in 500 mL of a 0.1 N HCl solution for 1 hour at 37° C. using USP paddle method, 100 rotations per minute, and then placing the composition in 500 mL of a pH 7.5, 0.05 M phosphate buffer, for 72 hours at 37° C. using USP paddle method, 100 rotations per minute, and then determining the amount of the naltrexone HCl sequestered.