Effect of Stabilizing Agent on Stability of Dexamethasone

Sodium phosphate Injection

Dexamethasone sodium phosphate

,
1

10300

Dexamethasone sodium phosphate

electrolyte tonicity
sodium chloride

creatinine nicotinamide

caffeine disodium edetate

chelating agent sodium bisulfite
antioxidant
50 C 22
0

110 C 30
0

High Performance

Liquid Chromatography

90-115%

 nicotinamide 2%

w/v disodium EDTA ions

sodium bisulfite

1-sulfonate compound

dexamethasone sodium phosphate

ions sodium

bisulfite disodium EDTA

nitrogen oxidation
:, Dexamethasone sodium, phosphate

phosphate

air

Dexamethasone

sodium

Oxidation

oxidation

creatinine

creatinine

creatinine

1.
( 1)

1.1

electrolyte

sodium chloride
0.9% w/v (SC)
1.2

nicotinamide

1.00, 1.50, 2.00,

2.50, 3.00, 3.50 4.00

%w/v (N)
1.3

caffeine

0.1, 0.2, 0.35, 0.5, 0.7,

1.0 2.0 %w/v (C)

1.4

chelating agent

disodium edetate

0.01 %w/v (E)

1.5

antioxidant

sodium bisulfite
0.1 %w/v 0.2

%w/v (SB)

2. Dexamethasone

sodium phosphate injection

 Sodium citrate (ST)

1.0 g, sodium bisulfite (SB)0.1
g

3.
3.1

(Sterilization)

parabens

(Thermal

methyl paraben (MP) 0.5 %

stock solution 4 ml (5%w/v

w/v propyl paraben (PP)

propylene glycol) disodium
edetate

stock solution

2 ml

(0.5% w/v , )

Dexamethasone

sodium

phosphate 0.4389 g (
Dexamethasone

phosphate(D)

0.4 g) pH 7.0-8.5
1.0 N sodium hydroxide

100

ml membrane

filter pore size 0.45 m

vial type I
nitrogen

parabens )
Cap seal
1

method of sterilization)

110 C 30
0

3.2

(autoclaving,AC)

Dexamethasone

sodium phosphate injection

30 C
0

(RT) 50 C
0

(AT) 22

Performance

High

Liquid

Chromatography (HPLC)

L1 4 mm x 30 mm UV
detector 254 nm
Mobile

ST

MP

PP

(g) / 100 ml
SB

SC

0.4

1.0

0.2

0.02

0.1

0.4

1.0

0.2

0.02

0.1

0.9

B1

0.4

1.0

0.2

0.02

0.1

1.0

B2

0.4

1.0

0.2

0.02

0.1

1.5

B3

0.4

1.0

0.2

0.02

0.1

2.0

B4

0.4

1.0

0.2

0.02

0.1

2.5

B5

0.4

1.0

0.2

0.02

0.1

3.0

B6

0.4

1.0

0.2

0.02

0.1

3.5

B7

0.4

1.0

0.2

0.02

0.1

4.0

C1

0.4

1.0

0.2

0.02

0.1

0.1

C2

0.4

1.0

0.2

0.02

0.1

0.2

C3

0.4

1.0

0.2

0.02

0.1

0.35

C4

0.4

1.0

0.2

0.02

0.1

0.5

C5

0.4

1.0

0.2

0.02

0.1

0.7

C6

0.4

1.0

0.2

0.02

0.1

1.0

C7

0.4

1.0

0.2

0.02

0.1

2.0

0.4

1.0

0.2

0.02

0.1

0.9

F1

0.4

1.0

0.2

0.02

0.1

1.0

0.01

F2

0.4

1.0

0.2

0.02

0.1

1.5

0.01

F3

0.4

1.0

0.2

0.02

0.1

2.0

0.01

F4

0.4

1.0

0.2

0.02

0.1

2.5

0.01

F5

0.4

1.0

0.2

0.02

0.1

3.0

0.01

F6

0.4

1.0

0.2

0.02

0.1

3.5

0.01

F7

0.4

1.0

0.2

0.02

0.1

4.0

0.01

G1

0.4

1.0

0.2

0.02

0.1

0.1

0.01

G2

0.4

1.0

0.2

0.02

0.1

0.2

0.01

G3

0.4

1.0

0.2

0.02

0.1

0.35

0.01

G4

0.4

1.0

0.2

0.02

0.1

0.5

0.01

G5

0.4

1.0

0.2

0.02

0.1

0.7

0.01

G6

0.4

1.0

0.2

0.02

0.1

1.0

0.01

G7

0.4

1.0

0.2

0.02

0.1

2.0

0.01

I2

0.4

1.0

0.2

0.02

0.2

1.5

0.01

I3

0.4

1.0

0.2

0.02

0.2

2.0

0.01

I4

0.4

1.0

0.2

0.02

0.2

2.5

0.01

I5

0.4

1.0

0.2

0.02

0.2

3.0

0.01

0.01

* D = dexamethasone phosphate,

sodium bisulfite, SC = sodium chloride,

C = caffeine

phase

ST = sodium citrate, MP = methyl paraben,

N = nicotinamide,

PP = propyl paraben,

E = disodium edetate

0.01

monobasic

potassium phosphate
methanol 1:1
Flow rate 1.6 ml/min

HPLC 2

dexamethasone

phosphate

retention time 5
O stabilizing

relative standard deviation

agent

1.5%

control

% label

amount

110 C 30
0

90% 115%

(autoclaving)

( 7.12%)

98.5% 91.38 %

USP 24 (

Dexamethasone sodium phosphate

phosphate (C22H30FO8P)

115 %)

Dexamethasone sodium phosphate

dexamethasone

disodium

50 C 22
0

1.5%
A

electrolyte ion (sodium

SB =

chloride)

102.

99.8

93.

99.

94.

91.7

22

100.

98.4

93.

99.

95.

91.6

99.8

100.

92.

98.

88.

90.6

98.6

92.1

91.

94.

91.

88.

101.

95.0

94.

93.

89.

55.6

104.

94.8

95.

95.

91.

90.5

103.

95.7

95.

94.

91.

91.1

101.

94.0

95.

94.

92.

89.9

101.

97.2

92.

95.

92.

89.8

100.

95.5

94.

99.

90.

91.9

99.3

95.0

94.

98.

91.

92.3

101.

93.0

96.

99.

93.5

100.

92.6

94.

I2

93.

98.

91.0

99.6

92.7

94.

I3

99.

97.

92.1

99.3

99.9

91.

I4

I5

99.

98.

91.4

100.97%

110 C 30
0

85.96% ( 15.01%)

sodium ion

50 C 22
0

0.98 %

2 (%

O
A

amount)

lable

RT

AT

AC

98.5

97.0

91.

100.
97

1
2
3
4
5

7
1
2
3
4
5

00
80
0
0

00
00
00
00
00
20
3

10
23
0
0

78

09

01

97

84

52

26

00

24

70

50

62

68

57

11

51

4
5
6
7
1
2

4
5
6
7

RT = room temperature

70
30
20
60
60
40
70
40
10
10
30
10
30
00

20

00
30
20
50
80
50
10
60
30
70
10

70
00

70

AT

7
6

35
5
7

4
7

8
0

1
1
9

accelerated temperature

RT

AT

AC

99.

91.

92.5

38

30

90

99.9

85.

99.

92.

93.0

96

70

40

AC

Autoclaving

B1-B7

nicotinamide

stabilizing

agent

98.6-104.0%

110 C
0

30

C1- C7

caffeine

6.48-8.47 %

99.33-101.1%

O
2.2-9.12%

B3

5.72% O

3.8- 8.1%

6.83 %

C4

stabilizing agent

nicotinamide
nicotinamide

stabilizer

nicotinamide

caffeine 0.5%
4.33%

4.71%

caffeine 0.5% w/v

(C4)

nicotinamide 2 %w/v

(B3)

(T90)

caffeine 0.5%

w/v
nicotinamide

%w/v

E, F1-F7 G1-

G7
chelating agent (disodium EDTA)

tonicity

sodium chloride

nicotinamide

caffeine chelating
agent

disodium EDTA

I
antioxidant

sodium bisulfite

oxidation

I
F

sodium bisulfite
1-

sulfonate

nicotinamide 2%

w/v stabilizing agent

sodium ion

disodium

Dexamethasone

ions

sodium phosphate
ion

disodium

EDTA

EDTA

sodium bisulfite

1-sulfonate

compound

nitrogen

oxidation

nicotinamide 2% w/v

cyclodextrin

disodium

complexing agent

ion

dexamethasone

dexamethasone sodium phosphate

edetate

sodium bisulfite

22

sodium phosphate

dexamethasone sodium phosphate

ions

sodium bisulfite disodium

EDTA

1.
,

2. . .

3. E.M. Cohen. Analytical

profiles of drug substance,

vol 12. Acadamemic Press,

Stated Pharmacopcial

New York. pp.163-197.

convention, Inc. Rockville.

(1973)

4. J.C. Boylan et al. The

Handbook of Pharmaceutical
Exicipient.

5. J.T. Carstensen. Drug and the

pharmaceutical

6. science, vol 68. Drug Stability.

Maecel Dekker, New York.
pp.144-162. (1995)

7. T.C. Macek and R. Edward.

GB1 034 294. (1996)

8. T. Loftsson. US 472 954.

(1996)

9. W. Lund. The Pharmaceutical

Codex. Twelfth edition. The

Pharmaceutical Press, London.

Pp.824-827. (1994)

10. British Pharmacopoeia

1993. HMSO, London.
(1993)

11. The United State

Pharmacopoeia 23, The

National Formulary 18. United

Pp.475. (1995)