Pharmaceutical composition

1. 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.

2. The method of claim 1 , wherein the human is in the fed state when orally taking the composition, and wherein the area under the plasma concentration versus time curve for 6-beta-naltrexol for the human, at 168 hours (AUC last ) after administration of the composition, is 1057 pg*h/mL.

3. The method of claim 2 , wherein the time to maximum concentration for 6-beta-naltrexol (T max ) in the human's plasma, after orally taking the composition, is 57.29 hours.

4. The method of claim 2 , wherein the maximum concentration of 6-beta-naltrexol (C max ) in the human's plasma, after orally taking the composition, is 25 pg/mL.

5. The method of claim 1 , wherein the controlled release layer comprises a cellulose; a polyalkylene glycol; an anionic copolymer based on methacrylic acid and ethylacrylate; and a plasticizer.

6. The method of claim 1 , wherein the composition does not contain a bittering agent, a gelling agent, an irritant, or an emetic.

7. The method of claim 1 , wherein in said multi-layer pellets, antagonist is contained only in the antagonist containing layer.

8. The method of claim 1 , wherein in said multi-layer pellets, agonist is contained only in the agonist layer.

9. The method of claim 1 , wherein in said multi-layer pellets, the only agonist is the morphine sulfate.

10. The method of claim 1 , wherein in said multi-layer pellets, the only antagonist is the naltrexone HCl.