content_image/940405.jpg content_image/940406.jpg
about 2-20 wt%. These amounts may be adjusted to take into consideration the presence of any base-neutralizable species. 

[0048] Inorganic salts of weak acids include, ammonium phosphate ( dibasic ); alkali metal salts of weakacids such as sodium acetate, sodium borate, sodium metaborate, sodium carbonate, sodium bicarbonate, sodium phosphate (tribasic ), sodium phosphate ( di basic), potassium carbonate, potassium bicarbonate, potassium citrate, potassium acetate, potassium phosphate ( dibasic ), potassium phosphate (tribasic ); alkaline earth metal salts of weak acids such as magnesium phosphate and calcium phosphate; and the like, and combinations thereof. 

[0049] Preferred inorganic salts of weak acids include, ammonium phosphate ( dibasic) and alkali metal salts of weak acids. 

[0050] The amount of inorganic salts of weak acids included in the compositions 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 approximately 2-20 wt%. These amounts may be adjusted to take into consideration the presence of any base-neutralizable species. 

[0051] B. Organic Bases 

[0052] Organic bases suitable for use in the invention are compounds having an amino group, amido group, an oxime, a cyano group, an aromatic or non-aromatic nitrogen-contain› ing heterocycle, a urea group, and combinations thereof. More specifically, examples of suitable organic bases are nitrogenous bases, which include, but are not limited to, pri› mary amines, secondary amines, tertiary amines, amides, oximes, cyano (-CN) containing groups, aromatic and non› aromatic nitrogen-containing heterocycles, urea, and mix› tures thereof. Preferred organic bases are primary amines, secondary amines, tertiary amines, aromatic and non-aro› matic nitrogen-containing heterocycles, and mixtures thereof. 

[0053] For nitrogenous bases, the amount of enhancing agent will typically represent about 0.5-4.0 wt%, preferably about 0.5-3.0 wt%, more preferably about 0.75-2.0 wt%, of a topically applied formulation or of a drug reservoir of a drug delivery system or a patch. These amounts may be adjusted to take into consideration the presence of any base-neutralizable species. 

[0054] Still greater amounts of the nitrogenous base may be used depending on the strength of the base and the rate and/or quantity of release of the nitrogenous base preferably during the drug delivery period itself. 

[0055] Preferred organic bases are those whose aqueous solutions have a high pH or a high pKa (more preferably a pKa>9), and are acceptable as food or pharmaceutical addi› tives. Examples of such preferred organic bases are those listed below, along with their respective pHs ( or pKa values). 

<img src='content_image/940405.jpg'>

## Inorganic Salts ofWeakAcids 

<img src='content_image/940406.jpg'>

Iisted in the "Handbook of Pharmaceutical Additives" 2 

1isted in the PDA’s food additive database 

[0056] Amines are compounds that include at least one primary amino (-NH$_{2}$ ) group, mono-substituted (second› ary) amino group or di-substituted (tertiary) amino group. 

[0057] Primary amino groups, secondary amino groups, and tertiary amino groups may be generically grouped as encompassed by the molecular structure -NR$^{1}$R$^{2}$R 3 wherein R1, R 2 , and R $^{3 }$may be the same or different and are generally selected from the group consisting of H, alkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, hydroxyalkenyl, alkoxy› alkenyl, cycloalkyl, cycloalkyl-substituted alkyl, monocyclic aryl, and monocyclic aryl-substituted alkyl, all of which may be substituted with one or more nonhydrocarbyl substituents, e.g., 1 to 3 halo, hydroxyl, thiol, or lower alkoxy groups. 

[0058] Exemplary primary amines include 2-aminoetha› nol, 2-aminoheptane, 2-amino-2-methyl-1,3 propanediol, 2-amino-2-methyl-1-propanol, n-amylamine, benzylamine, 1,4-butanediamine, n-butylamine, cyclohexylamine, ethy› lamine, ethylenediamine, methylamine, a-methylbenzy› lamine, phenethylamine, propylamine, and tris(hydroxym› ethy 1 )aminomethane. 

[0059] Exemplary secondary amines include compounds that contain groups such as methylamino, ethylamino, iso› propylamino, butylamino, cyclopropylamino, cyclohexy› lamino, n-hexylamino, phenylamino, benzylamino, chloroet› hylamino, hydroxyethylamino, and so forth. Exemplary secondary amines include diethanolamine, diethylamine, diisopropylamine, and dimethylamine. 

[0060] Exemplary tertiary amines include compounds that contain groups such as dibutylamino, diethylamino, dimethy› lamino, diisopropylamino, ethylchloroethylamino, ethylcy› clopropylamino, methylhexylamino, methylcyclohexy› lamino, methylpropylamino, methylbenzylamino, methyl-p› chlorophenylamino, methylcyclohexylamino, methylphenylamino, methyltoluoylamino, and so forth. Exemplary tertiary amines include N,N-diethylaniline, N,N› dimethylglycine, triethanolamine, triethylamine, and trim› ethylamine. 

[0061] Amides are compounds that include an amido group that has the molecular structure -(CO)-NR$^{1}$R 2 where R 1 and R $^{2 }$can be the same or different, and are generally selected from the groups consisting ofH, alkyl, hydroxyalkyl, alkoxy› alkyl, alkenyl, hydroxyalkenyl, alkoxyalkenyl, cycloalkyl, cycloalkyl-substituted alkyl, monocyclic aryl, and monocy- 

-continued 

## Amines 

## Amides 

