Associated forms of nonsteroidal anti-inflammatory drugs and local anesthetics

A pharmaceutical solution composition suitable for topical administration comprising a dexketoprofen-lidocaine associated form;

• and a vehicle selected from the group consisting of a monovalent alcohol, a divalent alcohol, a trivalent alcohol, dimethyl sulfoxide, triacetin, propylene carbonate, and mixtures thereof,
• wherein the associated form contains dexketoprofen free acid and lidocaine free base in 1:1 weight ratio;
• wherein the associated form does not include a covalent bond or an ionic bond between the dexketoprofen free acid and the lidocaine free base;
• wherein the associated form when subjected to characterization using infrared spectrum (IR) is missing IR peak at 1729 cm−1 and is missing a broad IR peak between 2000-2800 cm−1, wherein the IR peak at 1729 cm−1 represents —C═O stretching vibration of acid group in dexketoprofen and the broad peak between 2000-2800 cm−1 represents peak associated with salt formation between dexketoprofen free acid and lidocaine free base;
• wherein the associated form on topical administration to a subject provides extended release of the dexketoprofen free acid and the lidocaine free base;
• wherein the associated form or the solution composition does not include any excipient to extend the release of the dexketoprofen free acid and the lidocaine free base;
• and
• wherein the solution on topical administration to a subject provides a mean Tmax range for dexketoprofen of from about 17 hours to about 37 hours.

A method for making a dexketoprofen-lidocaine associated form comprising mixing dexketoprofen free acid and lidocaine free base in 1:1 wt ratio or in 1:1 molar ratio;

• wherein
• the associated form does not include a covalent bond or an ionic bond between dexketoprofen free acid and lidocaine free base;
• wherein the associated form when subjected to characterization using infrared spectrum (IR) is missing IR peak at 1729 cm−1 and is missing a broad JR peak between 2000-2800 cm−1, wherein the IR peak at 1729 cm−1 represents —C═O stretching vibration of acid group in dexketoprofen and the broad peak between 2000-2800 cm−1 represent peaks associated with salt formation between dexketoprofen free acid and lidocaine free base;
• wherein the associated form provides extended release of dexketoprofen free acid and lidocaine free base;
• wherein the associated form on topical administration to a subject provides a Tmax range for dexketoprofen of from about 17 hours to about 37 hours;
• and
• wherein the associated form does not include any excipient to extend the release of the dexketoprofen free acid and the lidocaine free base.

A method for treating a patient suffering from pain associated with arthritis comprising topical administration of a solution composition comprising a dexketoprofen-lidocaine associated form;

• and a vehicle selected from the group consisting of a monovalent alcohol, a divalent alcohol, a trivalent alcohol, dimethyl sulfoxide, triacetin, propylene carbonate, and mixtures thereof;
• the associated form contains dexketoprofen free acid and lidocaine free base;
• and wherein the associated form does not include a covalent bond or an ionic bond between the dexketoprofen free acid and the lidocaine free base;
• wherein the associated form when subjected to characterization using infrared spectrum (IR) is missing IR peak at 1729 cm−1 and is missing a broad IR peak between 2000-2800 cm,% wherein the IR peak at 1729 cm represents —C═O stretching vibration of acid group in dexketoprofen and the broad peak between 2000-2800 cm−1 represent peak associated with salt formation between dexketoprofen free acid and lidocaine free base;
• wherein the solution composition on topical administration to a subject provides extended release of the dexketoprofen free acid and the lidocaine free base;
• wherein the associated form on topical administration to a subject provides a Tmax range for dexketoprofen of from about 17 hours to about 37 hours;
• and
• wherein the solution composition or the associated form does not include any excipient to extend the release of the dexketoprofen free acid and the lidocaine free base.