3

. .

3
1 2563

•
1. •
( ) -
2. -
-
( ) - reverse osmosis
-
 ( )
•
1. (Surface water)
- Purified water
- Highly purified water
- Water for injection
- Sterile water for injection
- Bacteriostatic water for injection
- Sterile water for irrigation

2. (Ground water) /
• electrolytes
1. (Potable water)
•
•
•
•
• ion •
- : Ca(HCO 3)2 Mg(HCO 3)2 • ?
- : CaSO 4 , CaCl2 , Ca(OH)2 Mg salts

( ) ( )
2. (Soften water) 3.
• (Deminerlised or deionized water, DI water)
• , •
• autoclave • lab
• /
• /
• (cooling system)
 ( )

4. (Purified water)
•
• ( RO)

(Potable water/Tap water) (Potable water)

1 15
3. (Sterilization or Decontamination )
1. Pre-treatment
2.1 Chlorination : 0.01 ppm
/
- (settling) 2.2 Iodination : 0.5-1.0 ppm
- 2.3 UV : (dose )
- 2.4 Ozonization :
- , ultrasonic, radiation 2.5 Filtration : 0.2 micron, 0.005 micron
2. Clarification : (filtration) 4. , activated charcoal
 2+ (Demineralized/Deionized water)
Ca2+ Mg2+ HCO3-, CO3-
• ion
•
• ion exchage resin cation anion
• Ca++, Mg++, Fe++
• zeolite (cation exchage resin)
• resin ( 3 10)
•
• DI
• resin
 Zeolite
http://www.astom-corp.jp/en/en-main2-neosepta.html : http://www.iza-online.org/
http://www.isgtw.org/feature/isgtw-feature-immense-database-
indispensable-materials

DI deionization
“ ” • ion
•
• : • /resin
• :
• resin
• :
• UV , Ozone
Mg++ Ca++ resin
 DI
•
purified water USP/BP

• ?
• . ....... 1
• ?
•
 reverse osmosis (RO)
• (99% ) (97% )
(97% ) pyrogen
• CO2, NH3
• RO membrane :
• ( 5 13)
• 25oC
• RO water for injection (WFI)
•
 (Distilled water)
•

• ( 6 15)
- (boiler)
- (condenser)
 • DI RO
• Single-effect still : ( 6 15)
• PW DI silica
• Multiple-effect still : ( column )
( 7,8 15, • ions,
16) bacteria pyrogen
• Vapour compression still : • water for injection (WFI) RO
•

Water for injection (WFI) USP

• (distillation) RO
• 24
• 70oC
9 17
•
(PIC/S GMP 1 Sep. 2009)
 Pharmaceutical waters ( USP)
• Purified water (PW)
• Highly purified water ( EP) • Water for Final rinse
• Water for injection (SWFI) • Clean Steam
• Sterile water for injection
• Sterile Bacteriostatic water for injection
• Sterile water for irrigation
• Sterile water for inhalation

• Lipopolysaccharide (LPS) from the cell enveope that

is external to the cell wall of Gram-negative bacteria
• Endotoxins may be associated with either living
microorganisms or fragments of dead
microorganisms, or they may be free molecules.
• Endotoxins (>121)
( 0.2 micron RO )
( )
 (Purified waters) (Purified waters)
• monograph water PW
( ozone ) • PW

, ion exchange, reverse osmosis

ozone
( DI Ozone..) 70
pH 5.0 – 7.0 • PW
TOC (500 ppb), Conductivity (1.3 µS/cm) USA ( USP 33, Environmental Protection Agency: EPA, National Primary
(100 CFU/ml) Drinking Agency: NPDWR)
coliform, Pseudomonas aeruginosa EU
Burkholderia cepacia Japan
PW 0.22 µm •EP Endotoxin <0.25 EU/ml PW dialysis soluitons
100 ml 10 CFU/ml Pseudomonas species

Highly purified waters ( EP) (Water for Injection)

•
( ) WFI (EP)
(USP)
• double pass RO <5 >70
(UF DI)
• Endotoxin WFI pH 5.0 – 7.0
TOC (500 ppb), Conductivity (1.3 µS/cm)
(0.1 CFU/ml)
• coliform, Pseudomonas aeruginosa, Burkholderia cepacia
Pyrogen (Endotoxin <0.25 EU/ml)
Requirements for Purified Water (PW) Requirements for Water for Injection (WFI)
<500 ppb <500 ppb • Conductivity <1.3 µS/cm <1.3 µS/cm
<3.2 ppm
<0.1 CFU/ml < 0.1 CFU/ml
-
• Bacteria
• Conductivity <1.3 µS/cm <5.1 µS/cm
• Bacterial Endotoxins <0.25 EU/ml <0.25 EU/ml
• Bacteria <100 CFU/ml <100 CFU/ml
_________________________________________________________
• Nitrate - <0.2 ppm Highly Purified Water - EP
• Heavy Metal - <0.1 ppm As WFI

PW WFI (Sterile water for Injection)

2
, aseptic technique
WFI
5, 10, 20, 30, 50, 100, 250, 500 1000 ml
2 single-dose Type I Type II

isotonic solution
pH 5.0 – 7.0
WFI TOC (500 ppb), Conductivity (1.3 µS/cm)
bacterial endotoxin Pyrogen, Sterility
 Bacteriostatic water for Injection Sterile water for Irrigation

WFI
WFI 250, 500, 1000, 1500, 2000 3000 ml single-dose
2, 10, 30 ml single-dose multiple-dose Type I Type II
Type I Type II 1000 ml
30 ml

pH 4.5 – 7.0 SWFI

TOC (500 ppb), Conductivity (1.3 µS/cm) TOC (500 ppb), Conductivity (1.3 µS/cm)
Pyrogen, Sterility, Pyrogen, Sterility

Sterile water for Irrigation ( )

Surgical Irrigation Solutions (Splash solutions) Water for Final rinse
• •
•
• “ ” Sodium Chloride for Irrigation, Sterile
Water for Irrigation
Urologic Irrigation Solution
•

• 3000 ml
• Sterile Water for Irrigation, Sterile Glycine Solution for Irrigation
•
 Clean Steam
•

( )
• . . 458506
6. . • . .
• . . : , , , ,
; 2537. , . ;
2532.
• . . ;
2557. • . Pharmacopoeia and GMP Requirements for Pharmaceutical Water
System. GMP PIC/S
• .
5 28-29 2554
. cited 4 June 2007, available from:
.
htpp://wwwapp1.fda.moph.go.th/drug/zone_gmp/gmp-know2.asp
• . Water Purification Process.
• . .
GMP PIC/S 5 28-
2540; 23 (1): 23-34.
29 2554
• ( ). . : , , .
, ( ). • Meltzer, T.H. Pharmaceutical Water: Generation, Storage, Distribution and Quality
Testing. In: Groves, M.J., Olson, W.P., Anisfeld, M. H., editors. Sterile Pharmaceutical
• ( ). . : , Manufacturing, vol I. Illinois: Interpharm Press; 1991.
, , ( ).