Aug. 30, 2012  6  US 2012/0220962 Al  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).  [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- Amides  Amines  1  Iisted in the "Handbook of Pharmaceutical Additives"  2 1isted in the PDA’s food additive database  Inorganic Salts ofWeakAcids  -continued  Organic base  2-amino-2-methyl-1,3- propanediol  1  2-amino-2-methyl-1-propanol 1  Diethanolarnine 1  pH of Aqueous Solution (concentration)  10.8 (0.1 m)  11.3 (0.1 m)  11.0 (0.lN)  Organic base  Triethanolarnine 1  Butylamine 2  Dimethylamine 2  Cyclohexylamine 2  Ethylenediamine 2  Isopentylamine 2  Monoethanolarnine 2  Phenethylamine 2  Piperidine 2  Pyrrolidine 2  Trimethylamine 2  pH of Aqueous Solution (concentration)  10.5 (0.lN)  pKa- 10.56  Strong base, pKa - 10.73  Strong base, pKa - 10.64  Strong base, pKa - 10.71  pKa - 10.6  12.1 (25%), 12.05 (0.1 N), pKa - 9.4  Strong base, pKa - 9.83  Strong base, pKa - 11.12  Strong base, pKa - 11.27  Strong base, pKa - 9.81 