??

PHARMACEUTICAL SALTS: Table 1. Acids: Alphabetical Oi.der

PROPERTIES. SELECTION, AND USE

Table I (cont.)

335

pK,?

:lass Acid

lMr

pKa~

pKa2

I
1 l~cetic acid

AD1 up to [lngkg
11,s.

;RAS Status

Class Acid

M,

pK,z

pK,,

AD1 GRAS up to Status [mg/kl

3
1
2

Acetic acid. 2.2-dichloroAdipic acid Alginic acid L-Ascorbic acid L-Aspartic acid Benzenesulfo~licacid Benxoic acid Benzoic acid, 4-acelamido(+)-Camphoric acid (+)-Camphor- 10-sulfonic acid Capric acid (rlecanolc acid) Caproic acid (hexanoic acid) Caprylic acid (octanoic acid) Carbonic acid Cinnamic acid Citric acid Cycla~nic acid Decanoic acid (see cupric acid) Dodecylsulfuric acid Ethane-1.2-disullonic acid Erhanesulfon~cacid Erhanesulfonic acid, 2.hydroxyFornlic acid Fumaric acid Galactaric acid Gentisic acid u-Glucohrptonic acid D-Gluconic acid u-Gluctlronic acid Glutamic acid Glutaric acid Glurnric acid, 2-0x0Glycerophosphoric acid

60.05 128.95 146.14 240 000 176.13 133.11 158.18 122.12 179.18 200.24 232.29 172.27 6 6 144.22 44.01 148.16 192.13 179.24 266.40 190.20 110.13 126.13 46.02 116.08 210.14 154.12 226.18 196.16 194.1J 147.13 132.12 146.10 172.08

4.756 1.35 4.44

2.4

3
1

Hydrobromic acid Hydrochloric acid lsobutyric acid DL-Lacric acid Lactobionic acid Lauric acid Maleic acid (-)-L-Malic acid Malonic acid DL-Mandelicacid Methanesulfonic acid Mucic acid (see galacraric acid)

80.92 36.46 88.1 1 90.08 358.30 200.32 116.08 134.09 104.06 152.15 96.10

<-6 -6 4.86 3.86 3.2

4.9

2 1 2

1 1

4.17 1.88 0.7 4.19

1
1 1

2
2

1.92 3.459 2.826 3.372 -1.2

3 2 3
1

4.3 4.7 16 2.1 7

4.9 4.8 4.9 1 6.46 4.404 3.128

2 3 2
2

2
1

2
2
2

Naphthaicne-1,s-disulfonic acid 1332.26 Naphthalene-2-sulforlic acid 208.24

2-Naphthoic acid. I-hydroxyNicotinic acid Nitric Acid Octanoic acid (see capr?;lic acid) Oleic acid Orotic acid Oxalic acid Palmitic acid Pamoic acid (emhonic acid) Phosphoric acid Propionic acid (-)-L-Pyroglutamic acid Salicylic acid 188.17 123.11 63.02 282.45 156.10 90.04 256.42 388.38

-3.37
0.17

2.7
4.8: -1.32
cn. 4

3
1

2
2

-2.01
-0.09

3
2

2 2 2
3
1

-2.1 2.05
1.66

2 2 1 2
1

5.85
1.271 4.9 2.51 1.96 4.87 3.32 2.97 3.25 4.59 4.9 4.207 -3 3.02

3.75 3.03 3.08 2.93

1 2
1 1

2 2
3

I:
129.1 1 138.12 153.14 202.25 284.49 118.09 98.08 150.09 59.09 172.21 184.27

1
1
1

3.3 3.76 3.18 2.19

4,34

3 ISalicylic acid. 4-amino1 Sebacic acid

I
1

SlFariCacid Succinic acid Su1ful.i~ acid (+)-L-Tartaric acid Thiocyanic acid p-Toluenesulfonic acid Undecylenic acid (undec- 10-enoic acid)

2 1

2.7
1.47 3.28
3.55

1
1

76.05 Glycolic acid Hexanoic ;~cld (see ciiproic acid) 179.17 1 Hippuric acid

1 2

-1.33
-1.34
4.9

vl

5
7

+
- 2 2

+ +
m

vl

2
b

+ I Q

9a h ='5
c c

+
L Q

c
4
0

2 U
5

m
.?
N

E:

3
4 4 4

z
g q
&

2 w .-

N
4 4 4 4 4

io

r'

m
4 4 4 4 4 4 4 4

a a ~ y -

w N

\D

I A m P I ' q ? -

v ,

N *

-rW n

m N a m

5C q bi . b

2 2 2

-Q

>-.
-

g
v I

I -I

4
~ , ~ ~ N ~ C ~ ~

, Z . 1 I- . 2 I - I

N a a m o + - m , z z ~ q g . l ? m oo lm" ~? m o m o *? w ?m F
E

'

"

~
0

~C<

~ m

-z >
$

3
T

s-

~ ~ 9 9

~
9 ~ 1a- m ~ a i G % & 6 & i i & m , , , m a m a g~ n 8 ~ 9 ~~ ~ u d m m ~ a ~ N m ~ ~

A
u

0
Pi

$
n r ,

rcl

338

PHARMACEUTICAL SALTS: Table 3. .Acids: Sorted by hzcreusiiig Molec~~lulWeight

PROPERTIES, SELECTION, AND USE

Table 3 (cont.)

339

I I
Decanoic acid (see cap)-icuci0) Hexanoic acid (see cup!-oic acid) Mucic acid (see galucruric ucid) Octanoic acid (see cupplic acid) 1 1
3

Class Acid

1 3 1 36.46 44.01 46.02 59.09 60.05 63.02 74.08 76.05 80.92 88.11 90.04 90.08 96.10 98.00 98.08 104.06 110.13 116.08 116.08 116.16 118.09 -6 6.46 3.75
-1.33

Glutamic acid Cinnamic acid (+)-L-Tartaric acid DL-h,landelic acid Salicylic acid. 4-aminoGer~tisic acid Orotic acid Beozenesulfonic acid Glycerophosphoric acid p-Toluenesulfonic acid Capric acid (decanoic acid) L-Ascorbic acid Hippuric acid Benzoic acid. 4-acetamidoCyclamic acid Undecylenic acid (undec- 10-enoic acid) 2-Naphthoic acid, I-hydroxyEthane-1,2-disulfonic acid Citric acid D-Glucuronic acid U-Gluconic acid (+I-Camphoric acid Lauric acid Sebacic acid Naphthalene-2-sulfc~nicacid Galaclaric acid D-Glucoheptonic acid (+)-Camphol--10-sulfonic acid Palmitic acid Dodecylsulful~icacid Oleic acid Stearic acid Naphthalene- 1,s-disulfouic acid Lactobionic acid Pamoic acid (ernbonic acid) Alginic acid

7
Status

Hydrochloric acid

3 3
2 2 2

Gal-bonic acid
Forniic acid Thiocyanic acid Acetic acid Nitric Acid Propionic acid Glycolic acid Hydrobromic acid Isobutyric acid Oxalic acid DL-Lactic acid Metha~iesulfoilic acid Phosphoric acid Sulfuric acid Malonic acid Ethanesulfonic acid Fumaric acid Maleic acid Caprolc acid (hexanoic acid) Succinic acid Benzoic acid

1 1

4.756 -1.32 4.87 3.28

1 2 1 1 1

3
2 1

3
2 2
1

< -6
4.86 1.27 1 3.86 -1.2 1.96 -3 2.826

3
2

3
2 2 1

2 1 1 2 2 1 1

2.05
3.03 1.92 4.8 4.207
4.85 1.66

1
1

2
1 1 2 1 1

3
1

2 2
2

Nicotinic acid 23.1 1 Ethmesulfonic arid. 2-l1yd1~0xy-(126.13 Acetic acid. 2.2-dichloro(-)-L-Pyroglutamic acid Glutaric acid L-Aspartic acid 134.09 128.95 129.1 1 132.12

3 2
1
1

1.35 3.32 4.34 3.459

3
1 2 2

1
2 2 2

146.10 146.14 4.44

-

340

PHARMACEUTICAL SALTS:
Table 4. Acids: Sorted by Class

PROPERTIES, SELECTION, AND USE

34 1

I
pK,3 AD1 GRAS up to Status [mglkgl

Table 4 (cont.)
Acid
Mr
PK~I PKS pKa, AD1 GRA.! up to Status Imglkgl n.s.

Acid

Mr

pK3 I

pKaz

Decanoic acid (see capr.rc a c i d ) Hexanoic acid (see c(ip!-oicacid) blucic acid (see galactaric arid) 10ctanoic acid (see caprvlic acid) Class 1 Acetic acid Adipic acid L-Ascorbic acid L-Aspartic acid Capric acid (decanoic acid) Carbonic acid Citric acid Furnaric acid Galactaric acid D-Glucoheptonicacid D-Gluconic acid D-Glucuronic acid Glutamic acid Glutnric acid Glycerophosphoric acid Glycolic acid Hippuric acid Hydrochloric acid DL-Lacticacid Lauric acid Maleic acid (-)-L-Malic acid Paltnitic acid Phosphatic acid Sebacic acid Straric acid Succinic acid Sulfuric acid (+)-L-Tartaric acid Thiocyanic acid Class 2 Alginic acid Benzenesulfonic acid Benzoic acid 240 000 2 2.4 0.7 158.18 122.12 4.19
A

(+)-Camphoric acid Caprylic acid (octanoic acid) Cyclamic acid Dodecylsulfuric acid Ethane-1.2-disulfonic acid Ethanesulfonic acid Ethanesulfonic acid, 2-hydroxyGentisic acid Glutaric acid, 2-0x0Isobutyric acid Lactobionic acid MaIonic acid Methanesulfonic acid

200.24 144.22 179.24 266.40 190.20 110.13 126.13 154.12 146.10 88.1 1 358.30 104.06 96.10 208.24 188.17 123.11 282.15 156.10 90.04 388.38 74.08 129.11 172.21

4.716 4.9 1

A 5.83

A
A

- -2.01
-0.09

A
A -1.5 A A A A4.5 A A

-2.1 2.05 1.66 2.93

2.7
4.86 3.2 2.826 -1.2 -3.37 0.17 2.7 4.85
ca. 1

A A 5.696
A A -2.64

A A A

Naphthalene-l,5-disulfonic acid 332.26

Naphthalene-2-sulfonic acid 2-Naphtlloic acid, I-hydroxyNicotinic acid Olzic acid Orotic acid Oxalic acid Pamoic acid (embonic acid) Propionic acid (-)-L-Pyroglutamic acid

A
A 13.5 A 2.07 A

B
A A A
n.s.

5.85 1.271 2.51 4.87 3.32 -1.34

A8.95 A 4.266
A 3.1 A

I
I

1
I

p-Toluenesulfonic acid Class 3 Acetic acid, 2,2-dichloroBeuzoic acid, 4-acetamido(+)-Camphor-10-sulfonic acid Caproic acid (hexanoic acid) Cinna~nic acid Formic acid Hydrobromic acid DL-Mandelic acid Nitric Acid Salicylic acid

A
A A A A A A
A

128.95 179.18 232.29 1 16.16 148.16

1.35 4.3 2.17 4.8 4.404 3.75

46.02 80.92 152.15 63.02 138.12 153.14 184.27

c-6
3.372 -1.32 2.97 3.25

A A A 13.82 A A I0 A
A

n.s.

+ +

Salicylic acid, 4-aminoUndecylenic acid (undec-10-enoic acid)

3.5

A A

4.9

ri

ri

m m m

m m

m m

m m m m m m m m m m m m m m m m

m m m m m

m m m m m

Pi

m m m m m m m m m

m m m m m m m m m m m m m m

2
9 P

o m l n m rn r?r ?v-oIqq 0 c

ffi

C Z 2 3 - P

; f $ Z

* 3 ~

O \ ' mr* o ~ q rg ! ~ - ~ . ~ ~ 9 - , = c ~ ~ ~d d ~ - o & $ - m N L ? C\

o O 2
, - a -

' m

m m m m m m m m m

m m m m m m m m m m

rn
m m m m m m

F a -

7
'0
m

m m
t'?N
-

m
G ' cn
-f

m
m

8 - m
- C O

0;

B
m m m m m m m m m m m m m

m m m m m m m m m m m m m