oxycodone difference

I believe it refers to the oxycodone salts. I was interested in your question and I thought this may help. I think it has to do with creating the "sustained or controlled release" forms of oxycodone and discusses their invention. Happy reading....

http://www.wipo.int/pctdb/en/wo.jsp?wo=1997045091&IA=WO1997045091&DISPLAY=DESC

SUSTAINED RELEASE OXYCODONE

FORMULATIONS WITH NO FED/FAST EFFECT

BACKGROUND OF THE INVENTION

The present invention relates to solid, controlled release oral dosage forms for use in the treatment of moderate to severe pain, which do not exhibit a altered absorption of active ingredient in the presence of food.

It has been previously known in the art that controlled release oxycodone formulations could be prepared via sustained release coated bead or sustained release matrix formulations. For example, U.S. Patent No. 5,266,331, assigned to the assignee of the present invention and hereby incorporated by reference in its entirety, teaches controlled release oxycodone formulations prepared utilizing a suitable sustained release matrix. The preparations described in the '331 patent preferably exhibit an in-vitro dissolution rate of the dosage form, when measured by the USP Paddle Method at 100 rpm in 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37o C, which is between 12.5 and 42.5% (by wt) oxycodone released after 1 hour, between 25 and 55% (by wt) released after 2 hours, between 45 and

75% (by wt) released after 4 hours and between 55 and 85% (by wt) released after 6 hours, the in-vitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form. It further known that suitable sustained release oxycodone formulations are prepared using sustained release coated spheroid formulations, as described in U.S. Patent No. 5,508,042 (Oshlack et al.) assigned to the assignee of the present invention and hereby incorporated by reference in its entirety.

There is a need in the art for controlled release formulations that do not exhibit a food effect.

--> SUMMARY OF THE INVENTION

The present invention is directed in part to sustained release formulations of oxycodone which do not have a significant fed/fast effect, and methods for the preparation of the same. The sustained release oxycodone formulations of the present invention comprise an effective amount of oxycodone or a pharmaceutically acceptable salt thereof, and a sustained release carrier which preferentially causes the formulation to release the oxycodone in fluids having a relatively lower (acidic) pH.

The present invention is further directed to the preparation of sustained release oxycodone formulations which do not exhibit a significant fed/fast effect, which is accomplished by utilizing a sustained release carrier which preferentially causes the formulation to release the oxycodone in fluids having a relatively lower (acidic) pH.

The present invention is further directed to a method of treating patients in the need of analgesia with oxycodone in a manner which provides a sustained effect in-vivo, which effect does not significantly vary with respect to the gastric contents of the patient, by utilizing a sustained release carrier which preferentially causes the formulation to release the oxycodone in fluids having a relatively lower (acidic) pH.

In preferred embodiments of the invention, the oxycodone is in the form of the hydrochloride salt, or other pharmaceutically acceptable salts known to those skilled in the art, such as oxycodone terephthalate. The hydrochloride salt is preferred.

In further preferred embodiments of the invention, the sustained release carrier is an acrylic polymer, or other retardants such as cellulose polymers. The sustained release carrier may comprise part of a matrix or may be utilized as a coating on substrate containing the drug e.g., a tablet core or particles in a multi- particulate formulation.

--> For purposes of the present invention, "pH-dependent " means that the formulation provides a greater release in the amount of oxycodone released at acidic pH, e.g., pH 1.0 found in the human stomach, than the significantly higher pH's found in the intestinal tract, e.g., pH 7.6. More particularly, "pH-dependent", for purposes of the present invention, means that the sustained release oxycodone formulation includes a sustained release carrier which causes the formulation to possess a dissolution profile (rate of drug substance release) which is essentially insensitive to variations in dissolution media pH in the range of about pH 1.2 to about pH 6.8, and which possess a dissolution rate of drug substance release which decreases as the pH of the dissolution medium becomes basic. For puφoses of the present invention, "independent of pH" means that there is virtually no difference, at any given time, between the amount of oxycodone released at pH 1.6 and the amount released at any other pH up to, and including, pH 7.2 (when measured in vitro using the USP Paddle Method at 100 rpm in 900 ml aqueous buffer). In other words, the dissolution curves are virtually superimposible. The amounts released being, in all cases, a mean of at least three experiments.

For purposes of the present invention, the phrase "no fed/fast effect" means that there is less than 20% difference between the pharmacokinetic parameters (determined from blood levels of active drug) with respect to the valves for maximum blood plasma concentration (i.e., C-^ and area under the curve (i.e.,

AUC) obtained when patients are dosed with the formulation on an empty stomach as compared to when the drug formulation is administered to patients who have ingested a high-fat meal, as defined by the U.S. Food and Drug Administration or corresponding foreign regulatory body (i.e., the "fed state") and a food effect is considered to exist, where these differences are greater than 20%.

The term "sustained-release" for purposes of the present invention means that the oral dosage form provides a release of the oxycodone contained therein over a period from about 8 to about 24 hours or more. The sustained-release

-->formulations of the present invention preferably release the drug (e.g., oxycodone) at such a rate that blood (e.g., plasma) levels are maintained within the therapeutic range but below toxic levels over a period of time greater than 8 hours, more preferably for about 12 to about 24 hours, or longer.

The term "bioavailable" is defined for purposes of the present invention as the total amount of a drug substance that is absorbed is considered to be substantially equivalent as compared to the immediate release dosage form, to provide the desired therapeutic effect after administration of a unit dosage form. Generally, the bioavailability of a given dosage form is determined by comparison to a known reference drug product, as commonly determined and accepted by Governmental Regulatory Agencies, such as the United States FDA