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[0041] Inorganic hydroxides include, for example, ammo› nium hydroxide, alkali metal hydroxide and alkaline earth metal hydroxides, and mixtures thereof. Preferred inorganic hydroxides include ammonium hydroxide; monovalent alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; divalent alkali earth metal hydroxides such as calcium hydroxide and magnesium hydroxide; and combina› tions thereof. 

[0042] The amount of inorganic hydroxide included in the compositions and systems of the invention will typically rep› resent about 0.3-7.0 wt %, preferably 0.5-4.0 wt %, more preferably about 0.5-3.0 wt%, most preferably about 0.75- 2.0 wt %, of a topically applied formulation or of a drug reservoir of a drug delivery system, or patch. 

[0043] The aforementioned amounts are particularly appli› cable to those formulations and patches in which the active agent is (1) an uncharged molecule, e.g., wherein a basic drug is in nonionized, free-base form, (2) a basic salt of an acidic drug, or (3) there are no additional species in the formulation or patch that could react with or be neutralized by the inor› ganic hydroxide, to any significant degree. 

[0044] For formulations and patches in which the drug is in the form of an acid addition salt, and/or wherein there are additional species in the formulations or systems that can be neutralized by or react with the inorganic base (i.e., acidic inactive ingredients), the amount of inorganic hydroxide is preferably the total of (1) the amount necessary to neutralize the acid addition salt and/or other base-neutralizable species 

## Inorganic Hydroxides 

(i.e., the "acidic species"), plus (2) about 0.3-7.0 wt%, pref› erably 0.5-4.0 wt %, more preferably about 0.5-3.0 wt %, most preferably about 0.75-2.0 wt%, of the formulation or drug reservoir. That is, for an acid addition salt, the enhancer is preferably present in an amount just sufficient to neutralize the salt, plus an additional amount (i.e., about 0.3-7.0 wt%, preferably 0.5-4.0 wt%, more preferably about 0.5-3.0 wt%, most preferably about 0.75-2.0 wt%) to enhance the flux of the drug through the skin or mucosa! tissue. Basic drugs in the form of a neutral, free base or basic salt of acidic drug are usually not affected by a base, and thus for these drugs, the amount in (1) is usually the amount necessary to neutralize inactive components that are acidic. For patches, the afore› mentioned percentages are given relative to the total weight of the formulation components and the adhesive, gel or liquid reservmr. 

[0045] Still greater amounts of inorganic hydroxide may be used by controlling the rate and/or quantity ofrelease of the base, preferably during the drug delivery period itself. 

[0046] Inorganic oxides include, for example, magnesium oxide, calcium oxide, and the like. 

[0047] The amount ofinorganic oxide included in the com› positions and systems of the invention may be substantially higher than the numbers set forth above for the inorganic hydroxide, and may be as high as 20 wt %, in some cases as high as 25 wt% or higher, but will generally be in the range of 

## Inorganic Oxides 

