Prolonged Release Pharmaceutical Composition Containing 3-(3-Dimethylamino-1-Ethyl-2-Methyl-Propyl)Phenol

Abstract

A pharmaceutical formulation for prolonged release of the active ingredient 3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol or a pharmaceutically acceptable salt thereof in a matrix containing between 1 and 80 wt. % of at least one pharmaceutically acceptable hydrophilic or hydrophobic polymer as a matrix forming agent and exhibiting in vivo the following release rate: 3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours; 5 to 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 1 hour; 10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours; 15 to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours; 30 to 97% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 6 hours; more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours; more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation co-pending application Ser. No. 10 / 831,368, filed Apr. 26, 2004, which in turn was a continuation of international patent application no. PCT / EP02 / 11809, filed Oct. 22, 2002, designating the United States of America, and published in German as WO 03 / 035053, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application nos. DE 101 52 469.2, filed Oct. 24, 2001, and DE 102 48 309.4, filed Oct. 16, 2002.BACKGROUND OF THE INVENTION[0002]The present invention relates to a slow-release pharmaceutical formulation, containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof in a matrix.[0003]3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol is known from European patent no. EP 693,475 as an analgesic pharmaceutical composition and can be administered orally. Conventional formulations f...

AI Technical Summary

Benefits of technology

[0007]Accordingly, it is an object of the present invention to provide a pharmaceutical formulation which achieves slow release of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol.

[0016]more than 80% by weight of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours.It has surprisingly been found that the formulation according to the invention releases the active ingredient, 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, slowly when administered orally and is therefore suitable for administration at intervals of at least 12 hours. The formulation according to the invention therefore enables pain therapy, during which the analgesic, 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, only has to be administered once daily, for example at 24 hour intervals, or twice daily, preferably at 12 hourly intervals, in order to ensure an adequate concentration of the active ingredient in the plasma. A corresponding duration of efficacy and the maintenance of an adequate level in the blood plasma are demonstrated by simulation studies and experimental investigations.

[0017]It is particularly surprising that the formulation according to the invention not only ensures long-lasting therapeutic efficacy over a relatively long period (at least 12 hours) due to the slow release of the active ingredient, but at the same time allows the active ingredient to start flowing rapidly in the plasma when the pharmaceutical composition is first administered, leading to a rapid onset of pain relief in the patient. Therefore, the pain suffered by a patient can rapidly be alleviated when the formulation according to the invention is administered without the analgesic action quickly fading again. The formulation according to the invention therefore combines properties of a formulation with immediate release of active ingredient—rapid pain relief due to adequately high concentration of active ingredient just after administration of the pharmaceutical composition—with properties of a formulation having slow release—long-lasting analgesic action due to maintenance of an adequately high level of active ingredient over a prolonged time. By taking the analgesic in the formulation according to the invention, the patient can effectively combat his pain acutely and, at the same time, treat it effectively over a prolonged period without further measures and merely by regular administration at 12 (or 24) hourly intervals.

[0042]The production of pharmaceutical formulations according to the invention is characterized by high repeatability of the release properties of the resulting compositions containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof. The release profile of pharmaceutical compositions according to the invention has proven to be stable for a storage time of at least one year under conventional storage conditions according to ICH Q1AR Stability Testing Guidelines.

[0043]With once or twice daily administration of a pharmaceutical formulation according to the invention by the patient, good therapeutic efficacy is reliably achieved in the case of continuously strong pain.

Problems solved by technology

However, the need for frequent dosing easily leads to errors in administration and to undesirable variations in concentration in the plasma which are detrimental to patient compliance and the therapeutic benefit, particularly when treating chronically painful conditions.

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