Pharmaceutical compositions comprising a pH-dependent component and pH-raising agent

A method of treating pain in a subject in need thereof, comprising administering to the subject an immediate release oral pharmaceutical composition in unit dosage form comprising:

• (1) an inner first portion comprising:
• a first part comprising a core comprising an opioid selected from the group consisting of morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone and codeine, or a pharmaceutically-acceptable salt thereof;
• and a seal coating, comprising a cellulose resin covering the core;
• and a second part comprising an acid-sensitive coating comprising a pH-dependent polymer selected from the group consisting of cationic polymers containing a dimethylaminoethyl ammonium group, wherein the acid-sensitive coating is coated on the seal coating of the inner first portion, and releases the opioid at a pH below 4, and wherein the second part substantially covers the first part;
• and
• (2) an outer second portion comprising a pH-raising agent of one or more alkaline compounds selected from the group consisting of sodium bicarbonate, potassium bicarbonate, calcium carbonate, aluminum hydroxide and magnesium hydroxide;
• and
• wherein the second portion substantially covers the first portion;
• and wherein when two or more unit dosage forms of the oral pharmaceutical composition are administered to a subject within a time period of less than one hour, the amount and/or rate of the opioid released from the first portion is at least about 10% less than the amount and/or rate of the opioid released from the first portion when one unit dosage form is administered.