Transdermal administration of pharmacologically active amines using hydroxide-releasing agents as permeation enhancers
AssigneeDermatrends, Inc.
InventorsTsung-Min Hsu, Russell Macy, Eric C. Luo
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Abstract
Methods, compositions and drug delivery systems are provided for the transdermal administration of a pharmacologically active amine. The active agent is administered with a hydroxide-releasing agent that serves as a permeation enhancer. Exemplary hydroxide-releasing agents are inorganic hydroxides, inorganic oxides, and alkali metal or alkaline earth metal salts of weak acids. Inorganic hydroxides include, for example, ammonium hydroxide, alkali metal hydroxides and alkaline earth metal hydroxides, such as sodium hydroxide, calcium hydroxide, potassium hydroxide, magnesium hydroxide, and the like.
Claims77
A method for enhancing the flux of a pharmacologically active agent comprised of a nitrogenous base through a body surface, comprising administering the active agent to a localized region of a human patient's body surface in combination with a hydroxide-releasing agent, the hydroxide-releasing agent applied to the body surface in a predetermined amount effective to enhance the flux of the active agent through the predetermined area of the body surface without causing damage thereto, and effective to provide a pH in the range of approximately 8.5 to 13.0 at the localized region of the body surface, during active agent administration, wherein the active agent and hydroxide-releasing agent are present in a formulation and the amount of hydroxide-releasing agent in the formulation applied to the body surface is the total of (a) the amount required to neutralize any acidic species in the formulation plus (b) an amount equal to approximately 0.5 wt. % to 25.0 wt. % of the formulation.
A composition of matter useful for the delivery of a pharmacologically active agent through a body surface, comprising a formulation of:
- (a) a therapeutically effective amount of a pharmacologically active agent comprised of a nitrogenous base;
- (b) a hydroxide-releasing agent in an amount effective to enhance the flux of the active agent through the body surface without causing damage thereto and effective to provide a pH in the range of approximately 8.5 to 13.0 at the body surface, during active agent administration, and wherein the amount of hydroxide-releasing agent in the formulation applied to the body surface is the total of (a) the amount required to neutralize any acidic species in the formulation plus (b) an amount equal to approximately 0.5 wt. % to 25.0 wt. % of the formulation;
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- (c) a pharmaceutically acceptable carrier suitable for topical or transdermal active agent administration.
A system for the transdermal administration of a pharmacologically active agent, comprising:
- (a) at least one drug reservoir containing (i) a pharmacologically active agent comprised of a nitrogenous base and (ii) a hydroxide-releasing agent in an amount effective to enhance the flux of the active agent through the body surface without causing damage thereto, and effective to provide a pH in the range of approximately 8.5 to 13.0 at the localized region of the body surface, during drug administration, wherein the amount of hydroxide-releasing agent in the reservoir is the total of (a) the amount required to neutralize any acidic species in the reservoir plus (b) an amount equal to approximately 0.5 wt. % to 25.0 wt. % of the reservoir;
- (b) a means for maintaining the system in active agent- and enhancer-transmitting relationship to the body surface;
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- (c) an occlusive backing layer that serves as the outer surface of the system during use.
Dependencies are inferred from the claim text.