US 2013 0022646A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0022646 A1 Rudnic et al. (43) Pub. Date: Jan. 24, 2013 (54) CONTROLLED RELEASE FORMULATIONS (60) Provisional application No. 61/302.698, filed on Feb. OF OPODS 9, 2010, provisional application No. 61/386,277, filed on Sep. 24, 2010, provisional application No. 61/443, (76) Inventors: Edward M. Rudnic, Potomac, MD 966, filed on Feb. 17, 2011. (US); Michael Vachon, Quebec (CA); Gary W. Pace, La Jolla (CA) Publication Classification (51) Int. Cl. (21) Appl. No.: 13/442,849 A613 L/485 (2006.01) A6IP 25/04 (2006.01) (22) Filed: Apr. 9, 2012 A619/00 (2006.01) (52) U.S. Cl. ........................................ 424/400: 514/282 Related U.S. Application Data (57) ABSTRACT (63) Continuation-in-part of application No. 13/024.319, Pharmaceutical formulations containing opioid components filed on Feb. 9, 2011, Continuation-in-part of applica that each has a release profile. The components may provide tion No. 13/400,065, filed on Feb. 18, 2012, which is a immediate or controlled release of the opioid. The invention continuation-in-part of application No. 13/400,004, is also directed to methods of controlling release of one or filed on Feb. 17, 2012. more opioid compounds and methods of treating pain. Proposed Dosage Form Components Delayed and lodified Release Morphine Tablet Matrix with Disintegrantand Delayed and Delayed Release Oxycodone Modified Release Oxycodone Patent Application Publication Jan. 24, 2013 Sheet 1 of 32 US 2013/0022646 A1 Patent Application Publication Jan. 24, 2013 Sheet 2 of 32 US 2013/0022646 A1 peSeeled effeSOOOueoued 00200900900?70 Patent Application Publication Jan. 24, 2013 Sheet 3 of 32 US 2013/0022646 A1 ss state 3 C O O O O. O. O O. O C. 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In particular embodiments, a component may com CROSS-REFERENCES TO RELATED prise morphine and oxycodone, or salts thereof, in about a 3:2 APPLICATIONS ratio by weight. 0001. This application is a continuation-in-part of U.S. 0008. In some embodiments, the components may have an application Ser. No. 13/024.319, filed on Feb. 9, 2011, which immediate release profile or a controlled release profile. claims priority to U.S. provisional application Ser. No. 0009. In certain embodiments, the formulation may com 61/302.698, filed Feb. 9, 2010, and to U.S. provisional appli prise one or more additional components, such as at least two, cation Ser. No. 61/386,277, filed Sep. 24, 2010. This appli at least three, at least four, or at least five components. In some cation is also a continuation-in-part of U.S. application Ser. embodiments, the one or more additional components may No. 13/400,065, filed on Feb. 18, 2012, which is a continua comprise one or more active agents. In some embodiments, tion-in-part of Ser. No. 13/400,004, filed on Feb. 17, 2012, the one or more active agents may be compounds having which claims priority to U.S. provisional application Ser. No. opioid receptor agonist activity. In some embodiments, the 61/443.966, filed on Feb. 17, 2011. The entirety of each of one or more active agents may be one or more non-opioid these applications is incorporated herein by reference. analgesic compound(s), or a mixture of one or more non opioid analgesic compound(s) and one or more compound(s) FIELD OF THE INVENTION with opioid receptor agonist activity, or pharmaceutically 0002 The invention is directed to pharmaceutical formu acceptable salts, esters or prodrugs thereof. In certain lations comprising opioid components that each has a release embodiments, the one or more active agents may be one or profile. The components may provide immediate or con more hybrid opioid compound(s), or a mixture of one or more trolled release of the opioid. The invention is also directed to hybrid opioid compound(s) and one or more compound(s) methods of controlling release of one or more opioid com with opioid receptor agonist activity, or pharmaceutically pounds and methods of treating pain. acceptable salts, esters or prodrugs thereof. 0010. In embodiments of the invention, the pharmaceuti BACKGROUND OF THE INVENTION cal formulation may comprise a controlled release compo 0003) Opioids are a class of pain-relieving prescription nent, wherein the controlled release component comprises medications frequently used in the treatment of a variety of one or more cores. In additional embodiments, the controlled acute and chronic, moderate to severe, pain. However, opioids release component comprises oxycodone. In embodiments of can be rapidly absorbed and systemically excreted by the the invention, the pharmaceutical formulation comprises a body through metabolic inactivation. In order to treat steady state plasma concentration profile of the oxycodcone patients, especially those in severe pain, administration of having a fluctuation index of about 90% or less. In some opioids often requires careful dosing at frequent intervals to embodiments, the pharmaceutical formulation comprises an maintain effective steady state blood levels of the opioid, and AUC. Such that when the pharmaceutical formulation con thereby provide consistent analgesia. Otherwise, blood levels tains about 20 mg of oxycodone and the dosing interval is 12 of the opioid can oscillate, resulting in poor and inconsistent hours, AUC of oxycodone is about 100 ngh/mL to about pain relief.