Apr. 7, 2005  2  US 2005/0074487 Al  and (c) a pharmaceutically acceptable carrier suitable for  topical or transdermal drug administration. In one aspect of  the invention the pH is about 8.5-11.5, in another aspect the  pH is about 9.5-11.5, and most preferably about 10.0 to 11.5.  The formulation is typically aqueous. The pharmaceutically  acceptable base can be an inorganic or an organic base.  [0009]  Yet another aspect of the invention pertains to a  system for the enhanced topical or transdermal administra› tion of a drug, comprising: ( a) at least one drug reservoir  containing the drug and a pharmaceutically acceptable base,  in an amount effective to enhance the flux of the drug  through the body surface without causing damage thereto;  (b) a means for maintaining the system in drug and base  transmitting relationship to the body surface and forming a  body surface-system interface; and (c) a backing layer that  serves as the outer surface of the device during use, wherein  the base is effective to provide a pH within the range of  about 8.0-13.0 at the body surface-system interface during  administration of the drug. In one aspect of the invention the  pH is about 8.5-11.5, in another aspect the pH is about  9.5-11.5, and most preferably about 10.0 to 11.5. The  pharmaceutically acceptable base can be an inorganic or an  organic base.  [0010]  The present invention provides a method for  enhancing the flux of an active agent through a body surface.  The active agent and a basic permeation enhancer are  administered to a localized region of a human patient’s body  surface. The permeation enhancer is a pharmaceutically  acceptable base, and is present in an amount effective to: a)  provide a  pH  within the range of about 8.0-13.0 at the  localized region of the body surface during administration of  the drug and b) enhance the flux of the active agent through  the body surface without causing damage thereto. Examples  of suitable permeation enhancers are described below. The  active agent and permeation enhancer may be present in a  single pharmaceutical formulation, or they may be in sepa› rate pharmaceutical formulations.  [0011]  The steps of (a) administering the active agent and  (b) administering the basic permeation enhancer can be done  in any order. For example, step (a) can be done prior to step  (b); step (b) can be done prior to step (a); and steps (a) and  (b) can be done simultaneously. Certain methods may be  preferred depending upon the selection of active agent and  basic permeation enhancer, as well as taking into consider› ation ease of patient compliance and so forth. For example,  performing steps (a) and (b) simultaneously, is one preferred  method of the invention.  [0012]  I. Definitions and Nomenclature  [0013]  Before describing the present invention in detail, it  is to be understood that this invention is not limited to  particular drugs or drug delivery systems, as such may vary.  It  is also to be understood that the terminology used herein  is for the purpose of describing particular embodiments only,  and is not intended to be limiting. In addition, before  describing detailed embodiments of the invention, it will be  useful to set forth definitions that are used in describing the  invention. The definitions set forth apply only to the terms  as they are used in this patent and may not be applicable to  the same terms as used elsewhere, for example in scientific  literature or other patents or applications including other  applications by these inventors or assigned to common  owners. Additionally, when examples are given, they are  intended to be exemplary only and not to be restrictive.  [0014]  It  must be noted that, as used in this specification  and the appended claims, the singular forms "a,""an" and  "the" include plural referents unless the context clearly  dictates otherwise. Thus, for example, reference to "a phar› macologically active agent" includes a mixture of two or  more such compounds, reference to "a base" includes mix› tures of two or more bases, and the like.  [0015]  In describing and claiming the present invention,  the following terminology will be used in accordance with  the definitions set out below.  [0016]  "Active agent,""pharmacologically active agent"  and "drug" are used interchangeably herein to refer to a  chemical material or compound that induces a desired  pharmacological, physiological effect, and include agents  that are therapeutically effective, prophylactically effective,  or cosmeceutically effective. The terms also encompass  pharmaceutically  acceptable,  pharmacologically  active  derivatives and analogs of those active agents specifically  mentioned herein, including, but not limited to, salts, esters,  amides, prodrugs, active metabolites, inclusion complexes,  analogs, and the like. When the terms "active agent,""phar› macologically active agent" and "drug" are used, then, it is  to be understood that applicants intend to include the active  agent per se as well as pharmaceutically acceptable, phar› macologically active salts, esters, amides, prodrugs, active  metabolites, inclusion complexes, analogs, etc., which are  collectively referred to herein as "pharmaceutically accept› able derivatives". The term "active agent" is also intended to  encompass "cosmeceutically active agents", which are non› toxic agents that have medicinal or drug-like properties  which, when applied to the surface of skin, beneficially  affect the biological functioning of that skin.  [0017]  The term "aqueous" refers to a composition, for› mulation or drug delivery system that contains water or that  becomes water-containing following application to the skin  or mucosal tissue.  [0018]  The term "base" is used in its traditional sense, i.e.,  a substance that dissolves in water to produce hydroxide  ions. The water is typically an aqueous fluid, and may be  natural moisture at the skin surface, or the patch or compo› sition that is used may contain added water, and/or be used  in connection with an occlusive backing. Similarly, any  liquid or semisolid formulation that is used is preferably  aqueous or used in conjunction with an overlayer of an  occlusive material. Any base may be used provided that the  compound provides free hydroxide ions in the presence of  an aqueous fluid. Bases can provide free hydroxide ions  either directly or indirectly and thus can also be referred to  as  "hydroxide-releasing  agents".  Hydroxide-releasing  agents that provide free hydroxide ions directly, typically  contain hydroxide groups and release the hydroxide ions  directly into solution, for example, alkali metal hydroxides.  Hydroxide-releasing agents that provide free hydroxide ions  indirectly, are typically those compounds that are acted upon  chemically in an aqueous environment and the reaction  produces hydroxide ions, for example metal carbonates or  ammes.  [0019]  "Body surface" is used to refer to skin or mucosal  tissue.  DETAILED DESCRIPTION OF THE  INVENTION 