The invention provides compounds that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from those of the compound not attached to the water-soluble oligomer.

The presently described technology provides methods of treating a patient having moderate to severe pain, narcotic or opioid abuse or narcotic or opioid withdrawal. The presently described methods are carried out by comprising administering to the patient a pharmaceutically effective amount of a composition comprising acetaminophen and benzoate-hydrocodone hydrochloride. The composition has reduced side effects when compared with unconjugated hydrocodone.

The presently described technology provides methods of treating a patient having moderate to severe pain, narcotic or opioid abuse or narcotic or opioid withdrawal. The presently described methods are carried out by comprising administering to the patient a pharmaceutically effective amount of a composition comprising acetaminophen and benzoate-hydrocodone hydrochloride. The composition has reduced side effects when compared with unconjugated hydrocodone.

In certain embodiments the invention is directed to a process for preparing an oxycodone hydrochloride composition having less than 25 ppm of 14-hydroxycodeinone.

In certain embodiments the invention is directed to a process for preparing an oxycodone hydrochloride composition having less than 25 ppm of 14-hydroxycodeinone.

The present invention relates to opiate derived compositions and their antagonists useful in therapeutic areas associated with opioid receptor modulation,

A 3-hexadienoate modification of the opioids is formulated to improve opiates' engagement of the opioid receptors when given orally. A 3-hexadienoate modification of Nalbuphine or a pharmaceutically acceptable salt of thereof to improve quality of pain management when given intravenously, intranasally, transdermally, sublingually, rectally, topically, intramuscularly, subcutaneously or via inhalation.

A 3-hexadienoate modification of the opioids antagonists is formulated to improve inhibition of the opioid receptors when given orally. A 3-hexadienoate modification of Naloxone or a pharmaceutically acceptable salt of thereof to improve quality of Sobering when given intravenously, intranasally, transdermally, sublingually, rectally, topically, intramuscularly, subcutaneously or via inhalation.

The present invention relates to opiate derived compositions and their antagonists useful in therapeutic areas associated with opioid receptor modulation,

A 3-hexadienoate modification of the opioids is formulated to improve opiates' engagement of the opioid receptors when given orally. A 3-hexadienoate modification of Nalbuphine or a pharmaceutically acceptable salt of thereof to improve quality of pain management when given intravenously, intranasally, transdermally, sublingually, rectally, topically, intramuscularly, subcutaneously or via inhalation.

A 3-hexadienoate modification of the opioids antagonists is formulated to improve inhibition of the opioid receptors when given orally. A 3-hexadienoate modification of Naloxone or a pharmaceutically acceptable salt of thereof to improve quality of Sobering when given intravenously, intranasally, transdermally, sublingually, rectally, topically, intramuscularly, subcutaneously or via inhalation.

This invention relates to opioid ketal compounds of Formula (I), Formula (II), or Formula (III): or a pharmaceutically acceptable salts thereof, wherein R.sub.1 is H or CH.sub.3, R.sub.2 is H or OH, n is 0, 1, 2 or 3, R.sub.3 and R.sub.4 are independently or optionally substituted C.sub.1-C.sub.4 alkyl, or when n is 0, then R.sub.3 and R.sub.4 and the carbon atoms to which they are attached together form six, or seven membered ring, which is optionally mono or disubstituted by C.sub.1-C.sub.4 alkyl. The invention also relates to oxycodone ketal compounds of Formula (IV) or (V): or a pharmaceutically acceptable salts thereof. The invention also relates to the use of such compounds for the treatment, prevention, or amelioration of pain.

##STR00001##

This invention relates to opioid ketal compounds of Formula (I), Formula (II), or Formula (III): or a pharmaceutically acceptable salts thereof, wherein R.sub.1 is H or CH.sub.3, R.sub.2 is H or OH, n is 0, 1, 2 or 3, R.sub.3 and R.sub.4 are independently or optionally substituted C.sub.1-C.sub.4 alkyl, or when n is 0, then R.sub.3 and R.sub.4 and the carbon atoms to which they are attached together form six, or seven membered ring, which is optionally mono or disubstituted by C.sub.1-C.sub.4 alkyl. The invention also relates to oxycodone ketal compounds of Formula (IV) or (V): or a pharmaceutically acceptable salts thereof. The invention also relates to the use of such compounds for the treatment, prevention, or amelioration of pain.

##STR00001##

A method of recovering a highly pure hydrocodone base from an impure hydrocodone preparation includes contacting the impure hydrocodone preparation with a weak acid in water to form a solution and adding a strong base to the solution in an amount sufficient to precipitate the pure hydrocodone base product. A highly pure hydrocodone base comprises less than 0.0025 wt % codeinone.