Transdermal Delivery Of Systemically Active Central Nervous System Drugs

摘要

The invention relates to a transdermal or transmucosal non-occlusive, semi-solid pharmaceutical formulation that includes at least one systemically active agent that acts on the Central Nervous System (CNS) of a mammal; and a permeation enhancing solvent system present in an amount sufficient to solubilize the at least one active ingredient. The permeation enhancing solvent system includes a pharmaceutically acceptable monoalkyl ether of diethylene glycol; a pharmaceutically acceptable glycol; preferably also a fatty alcohol and or a fatty acid; and a mixture of a C2 to C4 alcohol and water so that the permeation enhancing solvent system (a) inhibits crystallization of the at least one active ingredient on a skin or mucosal surface of a mammal, (b) reduces or prevents transfer of the formulation to clothing or to another being, (c) modulates biodistribution of the at least one active agent within different layers of skin, (d) facilitates absorption of the at least one active agent by a skin or a mucosal surface of a mammal, or (e) provides a combination of one or more of (a) through (d).

主权项

1. A transdermal or transmucosal non-occlusive, semi-solid pharmaceutical formulation comprising:
at least one systemically active agent; and a permeation enhancing solvent system present in an amount sufficient to solubilize the at least one active ingredient and characterized in that it includes: (i) a pharmaceutically acceptable monoalkyl ether of diethylene glycol present in an amount of between about 1% and 30% by weight of the solvent system; (ii) a pharmaceutically acceptable glycol present in an amount of between about 1% and 30% by weight of the solvent system, wherein the monoalkyl ether of diethylene glycol and the glycol in combination are present in an amount of at least 15% and no more than 60% by weight of the formulation; and (iii) a mixture of a C2 to C4 alcohol and water, which mixture is present in an amount of between about 40% and 98% by weight of the solvent system, wherein the C2 to C4 alcohol is present in an amount of about 5% to 80% by weight of the mixture, and the water is present in an amount of about 20% to 95% by weight of the mixture;so that, compared to formulations not containing the present permeation enhancing solvent system, the present formulation (a) inhibits crystallization of the at least one active ingredient on a skin or mucosal surface of a mammal, (b) reduces or prevents transfer of the formulation to clothing or to another being, (c) modulates biodistribution of the at least one active agent within different layers of skin, (d) facilitates absorption of the at least one active agent by a skin or a mucosal surface of a mammal, or (e) provides a combination of one or more of (a) through (d).