WATER TREATMENT

WATER TREATMENT

What is the basic nature of water?

Water is a complicated and incompletely understood chemical compound with a number of peculiar characteristics. Fresh formed rain is the purest form of water. It is also its highest energy form. Considerable energy is expended by acquisition of solute impurities in passing from rain cloud to the final water tap.

How do impurities get into water?

Falling rain water passing through the air contacts carbon dioxide and sulfur dioxide, forming carbonic acid and sulphuric acid in weak solution. Upon meeting with the earth , water encounters lime stone and other minerals to form calcium bicarbonate and sulphate. Calcium carbonate is the most prevalent impurity in tap water and accounts for most of its hardness.

What other minerals may be present in tap water?

Sodium chloride , iron , magnesium, nitrates manganese , copper, zinc, iodide and fluoride are common ionic constituents. The types of minerals present in the geographic area and the time the water is in contact with them determine the content.

Trace elements present include arsenic, silver, strontium , selenium, chromium , lead, cadmium, cyanide, barium, tin and others.

Are these minerals harmful?  

Nitrates may cause methemoglobinemia – a situation in which red cell hemoglobin cannot transport oxygen. Copper in excess may cause hemolysis , pancreatitis or a type of hepatitis.

Manganese can be toxic and iron may possibly be so. Fluoride is believed by many to aggravate uremic bone disease but this is not proved. It does accumulate in bone and it is toxic to enzyme system.

Do the trace elements offered any hazard?

The effect of these is largely unknown. Tin has been found in significantly higher quantity in tissues of dialyzes uremic patients than in nonuremic individuals. Aluminum also accumulates  and has been tentatively related to the dialysis-dementia syndrome. Zinc causes gastrointestinal upset and may produce anemia,

Are there any other materials in tap water ?

Nonionic organic compounds particularly nitrogenous matter such as proteins an polypeptides , phenols, indoles and aldehydes may be present. Solid aprticles of iron. Sand and silica are frequent , Suspended material including mud, algae , plankton, bacteria viruses , pyrogenic matter and dissolved gases ( ammonia , carbon dioxide, chlorine ) are often present. The most common soluble organic compounds are chloramines resulting from urban water treatment systems. The content of these as well as of ionic impurities varies with the water sources , season and distribution system..

Why is special  treatment necessary for water used to make dialyzing fluid ?

During hemodialysis the amount of water that contacts the patient’s blood is 20 or more times the amount taken in by drinking. Water ingested by drinking is processed by gastrointestinal tract prior in reaching the bloodstream  This selective membrane can alter the rate at which foreign substances are absorbed from ingested  water. In a dialyzer system the water in dialysate  is separated from blood by a non living artificial membrane. The dialyzer membrane can not select ions to be absorbed or reject  and they pass diffusion. Thus ,substances hat might be harmless in drinking water may  be toxic in dialysis water.

What methods are used to treat water for use in hemodialysis ?

·         Filtration

·         Softening

·         Adsorption by activated charcoal

·         Deionization

·         Revers Osmosis ( RO )

                               

What is accomplished by filtration ?

Suspended particles ( mud, sand, rust, algae ) are removed by mechanical filtration through a wound filament or membrane cartridge. These effectively filter particles down to about 5 µin size. Filtration does not remove dissolved particles or ions from the water.

                
                                                     

How is activated charcoal used in water treatment ?

Activated charcoal acts by adsorption. It does not remove electrolytes such as  sodium or calcium . It has a unique ability to adsorb chloramines , odor-producing materials and lower molecular weight ( 60 to 300 daltons )material s as well higher molecular weight organic matter.

               

What does softening of water achieve?

 

Hardness of water is produced primarily by calcium and magnesium ions. Commercial softening units replace these diavalent ions with sodium ions from an exchange resin bed on a milliequivalent-for-milliequivalent basis. For each calcium ion removed ,two sodium ions are added .

If the water is very hard, the use of a softener will remove most of the calcium and magnesium ion prior to further treatment. . If a deionizer is used , the softener will reduce the divalent ion load presented to the deionizer resin bed and prolong its life. If the subsequent treatment is by RO the removal of calcium and magnesium by the  softener may result in higher quality water and longer RO membrane life. 

water softener
                                                                      

What problems occur with use of water softener ?  

If raw water is very hard ,considerable sodium is substituted by the exchange for calcium and magnesium. Municipal water supplies often vary  seasonably or even during a single day if multiple sources are used. Monitoring of softener function is done by checking the total ‘Hardness “ of outflow water and is difficult on a continuous basis.  

What is deionization ?

 

Ion exchange resins  somewhat like those of a water softener but most sophisticated, are used to remove both cations and anions from the processed  water.

                                  
                                                        
                                                                  Deionization                           

How does a deionizing  unit work ?

Essential are a cation bed and an anion bed . Each bed is composed of grains of ion exchange resin about the size of fine sand, called zeolite. Zeolites are large organic chemical molecules that have active side chain groups attached to them.. The side chain of the zeolite  in the carbon bed is a carbonyl ( -COOH ) group . In the anion resin bed there are attached substitute

Ammonium group ( NH3 and OH ). In passage through the cation bed calcium ,magnesium sodium and other cations in the water combine with the carboxyl radicals with the release of hydrogen ions. In the anion bed anions – chloride , fluoride , sulphate, nitrate, bicarbonate and others  are exchanged for the hydroxyl  ion (-OH) . The release hydroxide ion   combine with hydrogen ions released at the cation bed to form water chemically.

CATIONS                   ANIONS

Na                                            Cl

K                                             F

Ca                                            So4

Mg                                           NO3

CATION RESIN BED

H                                             Cl

H                                             F

H                                             SO4

H                                             NO3

ANION BED RESIN

   
H                             OH

                      

                                   H2O

Above  Schematic diagram of  de ionizing apparatus

What is the difference between two bed and single bed deionizer system ?

The two bed system has the cation removing and anion removing resins in separate tanks; water flows through the cation bed and then to the anion bed . The single bed or mixed bed system system has the two resin mixed together. The single bed system because of the mixing produces a much higher quality ( pure ) water. It is also more costly. 

What are problems in deionizer-use ?

1.         One problem is obtaining the maximum flow rate needed ( standard units  for center use have a maximum of  about 300 gallons per hour )

2.         The ionic of raw water presents a problem -  a finite quantity of ions can be removed  by a bed of given size, hence a lesser  volume of  water with a high content can be processed than if the content is low.. The life of the deionizer bed depends on water composition and / or volume .  

3.         Beds tend to exhaust suddenly, it is necessary  to  have parallel or twin installation  so that  a switchover  can be made while the exhaust of tanks are replaced.

4.         Sometimes during regeneration of the resin tanks channel form in the bed. Such a tank may exhaust in an abnormally short time. Usually the anion and cation resin s exhaust at different .times. Depending on which exhausts first , their may be an excess of H or  of OH ion  in the product water.

What is reverse osmosis ? (RO)

This is a process that utilizes semipermeable membrane and pressure to remove both organic matter and electrolytes from water . The membrane repel ions, Organic particles are screened out while water passes through the micropores of the membrane surface by ultrafiltration. These pores are approximate 200 nm in diameter.

                                 

                                                         Reverse osmosis                                                         

        

How does the membrane “repel“ electrolyte ?

This results from electrochemical tension at the water membrane interface, and increases with high valence salts. Diavalent ions such as calcium, magnesium are repelled at a greater distance from the membrane surface than  are monovalent ions ( Sodium ). The rejection rate for divalent ions is greater than 95 % and for monovalent ions 90 to 95 % . Thus up to 10 % of the ions in the feed water may remains in the final product ( purified ) water,

How are organic compounds processed by the membrane ?

Organic compounds have no net charge and are not electrically repelled but are physically screened , depending on molecular size & shape, by the mambrane. Almost all particles of molecular weight greater than 200 daltons are rejected. This includes bacteria, viruses, and known pyrogens.

OVERHEAD     ---------->      IRON REMOVER       --------->  WATER SOFTNER ------->

                                                                           

 <--------  DE                       <--------- CHAR COAL  <---------- CHLORINATION <-------

              CHLORINATION                   TREATMENT                     ( 5 ppm Chroline )                    

 

  ---------------->   DEMINERALIZATION  ------------>  DISTILLATION

Chlorination : 0.5 % Sodium Hypochloride solution  2 drops / 250 ml

KEY OF THE QUALITY PRODUCT IN PHARMACEUTICALS

We do think the key factors that smooth the quality production as well as their increasing market acceptance, are as following:

  PRODUCT DEVELOPMENT SECTION:

ü      According to product proposal they develop the formulation of a product, which ensure quality product within effective cost range.

ü   They are prepared a narrow in-house specification of raw materials/excipients that procured from the reliable vendor because quality raw materials ensure quality product.

ü      Analytical approach based on high performance sensitive equipments and efficient hands are ensured product quality until its shelf life.

ü   Prepared BMR and BPR so perfectly that the workers easily adapt it and meet fewer hazards during production.

ü      They also validate the process properly.

ü      Fortunately we have got chance to be involved in developmental process that enriched our theoretical knowledge as well as increase our interest. For this we are grateful to the administration.

   QA & QC DEPARTMENT:

 ü    The strong backup QA & QC with PD to the production section ensure claimed quality of product. QC perform the in process checking during production by using high tech instruments such as HPLC, FTNIR, FTIR, Atomic absorption spectrometer, Total organic carbon analyzer, Liquid particle counter, Gas chromatography etc.

 ü     QA have strong documentation process both manually and online (software) that facilitates to keep records of every step during production of a product.

 TABLET:

ü     Though it is a hazardous section, they know the art to produce a quality tablet without facing less problem as the man, material, machine- validated and almost dedicated to a product and latest tablet compression machine (Manesty Rotapress Diamond, Hanli-HLT-45, Cadmach, Sejong) and enrich BMR. From the following two examples it is clear-

ü      Wet granulation method of Ranitidine.

ü   The number of coating tablet (109) speaks about their efficiency in coating as it may hamper DT, Dissolution of tablet but the color of coating increase the acceptance.

 PARENTERAL:

It is theoretically possible but practically a tough job to maintain aseptic condition in parenteral section, liquid section. Though they have no separate building for penicillin & non-penicillin section but their sanitation system so well that they mostly overcome this limitation.

v     Recently a pet bottle section opened which meet up their in-house consumption and also speaks why they are called promising pharmaceutical.

v     Addition of automatic packaging machine increases productivity as well ass acceptance to the importer.

It seems to us that the following things may smooth their steps to the crest:

v     If pharmacists direct observation would possible to each step in every section.

v     If the software would more compatible with the level of employee

Factors of Parenteral Product

    PARENTERAL

We do think the key factors that smooth the quality production as well as their increasing market acceptance, are as following:

It is theoretically possible but practically a tough job to maintain aseptic condition in parenteral section, liquid section. Though they have no separate building for penicillin & non-penicillin section but their sanitation system so well that they mostly overcome this limitation.

*     Recently a pet bottle section opened which meet up their in-house consumption and also speaks why they are called promising pharmaceutical.

*     Addition of automatic packaging machine increases productivity as well ass acceptance to the importer.

It seems to us that the following things may smooth their steps to the crest:

*     If pharmacists direct observation would possible to each step in every section.

*     If the software would more compatible with the level of employee

Factors of Tablet

TABLET

We do think the key factors that smooth the quality production as well as their increasing market acceptance, are as following:

* Though it is a hazardous section, they know the art to produce a quality tablet without facing less problem as the man, material, machine- validated and almost dedicated to a product and latest tablet compression machine (Manesty Rotapress Diamond, Hanli-HLT-45, Cadmach, Sejong) and enrich BMR. From the following two examples it is clear

*    Wet granulation method of Ranitidine. 

* The number of coating tablet (109) speaks about their efficiency in coating as it may hamper DT, Dissolution of tablet but the color of coating increase the acceptance.

Factor of QA and QC In Pharmaceuticals

We do think the key factors that smooth the quality production as well as their increasing market acceptance, are as following:

QA & QC DEPARTMENT:

*   The strong backup QA & QC with PD to the production section ensure claimed quality of product. QC perform the in process checking during production by using high tech instruments such as HPLC, FTNIR, FTIR, Atomic absorption spectrometer, Total organic carbon analyzer, Liquid particle counter, Gas chromatography etc.

*    QA have strong documentation process both manually and online (software) that facilitates to keep records of every step during production of a product.

 

Product Development in Pharmaceuticals

PRODUCT DEVELOPMENT

 

-     According to product proposal they develop the formulation of a product, which ensure quality product within effective cost range.

-      They are prepared a narrow in-house specification of raw materials/excipients that procured from the reliable vendor because quality raw materials ensure quality product.

-     Analytically it high performance sensitive equipments and efficient hands are ensured product quality until its shelf life.

-     Prepared BMR and BPR so perfectly that the workers easily adapt it and meet fewer hazards during production.

-     They also validate the process properly.

-      Fortunately we have got chance to be involved in developmental process that enriched our theoretical knowledge as well as increase our interest. For this we are grateful to the administration.

LAL Test

LAL TEST(Limulus Amebocyte Lysate):

Introduction:

Limulus Amebocyte Lysate(LAL) is an aqueous extract of blood cells ( amebocytes) from th horseshoe crab, Limulus polyphemus  .In December 1987, the U.S Food and Drug Administration (FDA)          published the Guidelines on the validation of the Limulus Amebocyte Lysate test as an end-point endotoxin test for human & animal parenteral drugs., biological products & medical devices. The LAL test for pyrogen in parenterals was first applied by Cooper  et  al . The LAL test was found to be more accurate & time saving than pyrogen test.

Definition: 

LAL(Limulus Amebocyte Lysate) Test is the most sensitive and specific means to detect and measure endotoxin, a fever producing byproduct of  gram negative bacteria such as E.coli and Pseudononas commonly known as pyrogen. Endotoxin produces an opacity and gelation in LAL. The simplicity and economy of the LAL test encourages the testing of in- process solutions and raw materials, The LAL test is used as the replacement for the rabbit pyrogen test.

Principle:

Proenzyme  ----->  Endotoxin  -----> Coagulase

Coagulagen  -----> Coagulase  -----> Coagulin

Gram-negative bacterial endotoxin catalyzes the activation of proenzyme in the Limulus Amebocyte Lysate.  The concentration of endotoxin present  is determine the initial rate of activation . The activatied enzyme ( Coagulase ) hydrolyzes specific bonds within a clotting protein ( Coagulogen ) also present in Limulus Amebocyte Lysate . Once hydrolyzed, the  resultant coagulin self associates and forms a getatinous  clot .

 

Methods of Lat Test:

There are five methods of LAL test:

1)      Gelation Method : Limit Test

2)      Semi quantitative Getation Method

3)      Turbidimetric  Kinetic Method

4)      Chromogenic peptide Kinetic Method

5)      Chromogenic peptide endpoint Method .

Gelation  Method:

The Gelation or Gel–Clot LAL test Method  is a simple reproducible test that is conducted by mixing equal parts of Endosafe. LAL reagent and test specimen and promptly incubating the mixture in disturbed for 60 minutes at 37 °C . A positive response indicates that there is an amount of endotoxin in the sample which equals or exceeds the reagents labeled sensitivity.

Test Procedure :

1)   Add 0.1 ml /0.25 ml of each dilution to the assay tube ; test at least in duplicate.

2)   Add 0.1ml /0.25 ml of reconstituted standard to each tube starting with the – ve control & ending with the highest endotoxin concentration.

3)   Place the reaction tube in a 37°C water or dry bath for 60 ± 2minutes

4)   Observe the tubes for Gelatin . If gel is formed which retains after turning the tubes to 180°C, then the test is +ve for endotoxin . And if the gelation does not take  place, the test is – ve for endotoxin presence.

Conclusion:

As LAL is capable of detecting a very minute amount of endotoxin in product, hence it is now widely accepted throughout the world  in instead Pyrogen test.