Water for Pharmaceutical Use

1. Water Purification Engineering Water for Pharmaceutical Use Pharmaceutical Industrial Management Pharm 5211: Section B Md. Saifuzzaman Associate Professor Pharmacy Discipline, KU. E-mail: saifuzzaman17@yahoo.com Taken from

2. Objectives To examine the basic technology and requirements for: • Water treatment systems • Storage requirements • Sampling and testing • Different types of water used in pharmaceuticals • Microbial limits, disinfection

3. Water system design • Pipes sloped so water does not pool and can drain easily • Sanitary fittings & connections • Constructed of suitable materials such as stainless steel • Circulate the water • Incorporate non-return valves (NRV)

4. Further water treatment purification stages downstream of the pre-treatment system • Filtration • Disinfection • Reverse osmosis or de-ionization • Distillation or ultra-filtration

5. D Flow direction arrows on pipes are important Deadleg section X <2D If D=25mm & distance X isgreater than 50mm, we have a dead leg that is too long. Sanitary Valve Water scours deadleg Water system design There should be no dead legs

6. Water system design 1. Ball valves are unacceptable 2. Bacteria can grow when the valve is closed 3. The water is contaminated as it passes through the valve Stagnant water inside valve

7. Water system design • Sanitary pumps • Clamps and O rings versus threaded fittings • Heat exchangers • Side arm level measuring devices are unacceptable

8. Typical de-ionizer schematic from water softener HCl NaOH 6 6 5 5 4 4 3 3 2 2 1 1 Water must be kept circulating Anionic column Cartridge filter 5 µm Cartridge filter 1 µm Cationic column UV light Eluates to neutralization plant Ozone generator Hygienic pump Return to de-ioniser Outlets or storage. Drain line Air break to sewer

9. Up and Down Flow DOWNFLOW : No channeling and better ion capture, but higher risk of UPFLOW : clogging Channeling Used in but lower Polishing risk of clogging Used in Pretreatment

10. SEM of Ion-Exchange Resin Bead Bead diameter: 300 to 1200 µm (0.3 to 1.2 mm) Beads pores: 1 to 100 nm (0.001 to 0.1 µm) Bead dry weight 40 to 60%

11. Ion-Exchange Resin Bead model Fixed Anion Counter Cation Styrene Cross linking Agent (DVB) Hydrating Water

12. 1 2 1 2 Reverse Osmosis Reverse Osmosis Osmosis P Osmotic pressure 1 2 Reverse osmosis membrane (RO) Feed water Purified water

13. Low pressure High pressure Feed water under pressure Semi-permeable membrane Purified water raw water Reject water Permeate water drain or recycle Reverse osmosis (RO) theory

14. Reverse Osmosis Membrane Permeate Feed Water Reject

15. Typical 2-stage RO schematic Water from softener or de-ioniser Second stage reject water goes back to first stage buffer tank 1st stage buffer tank First stage RO cartridge Branch Branch 1st stage reject concentrate First stage filtrate feeds second stage RO with excess back to 1st stage buffer tank . Air break to sewer Second stage RO cartridge 2nd stage buffer tank High pressure pump Cartridge filter 1 µm Hygienic pump Second stage RO water meets Pharmacopoeia standards Water returns to 1st stage buffer tank Outlets or storage

16. Use of reverse osmosis • Advantages • Disadvantages • Many uses • purified water • feeding of distillation units or ultra-filtration units • Water for Final Rinse • Water for Injections (if permissible)

17. Ultra-filtration • Can be used for WFI or for Water For Final Rinsing for parenteral manufacturing (if permitted) • Removes organic contaminants, such asendotoxins • Operation at 80°C, and sterilization at 121 °C

18. Ultrafiltration • Ultrafilters are asymetric membranes, sometimes composite • Under pressure,small size molecules go through the membrane,whereas molecules larger then the NMWL are retained