NaOH Manufacturing Process

NaOH Manufacturing

Caustic soda (NaOH) available in solid flakes and liquid solution (different concentration. Caustic soda production is done by any one of the following manufacturing processes.

Method of Manufacture:

1.    Chemical: lime soda process,

2.    Electrochemical: chloro alkali process

§      Diaphragm Cell

§      Mercury Cell Process

§      Membrane Cell Process

Electrochemical Process

Castner-Kellner Cell (Mercury Cell Process)

Castner-Kellner process was developed in the mid 1800’s. The cell had a positive electrode and a negative electrode inside a tank. The reactions proceeded as follows:

1.  A sodium chloride brine (salt water) is put into the tank. 
2.  The positive electrode (Titanium anode) attracts the chloride away from the sodium. The chloride builds up and combines to form chlorine gas ( an excellent disinfectant)

Anode Reaction (oxidation: 

 2Cl- (aq)  = CL2 (g)+ 2e-

fig: mercury cell process

3         3. The water is broken apart with the negative electrode (Mercury cathode) into hydrogen ions) which form into hydrogen gas) and hydroxide ions.

           4. The negative electrode (Mercury electrode) attract sodium ions forming.

Cathode Reaction (reduction):

Na+(aq)  + e- = Na(s)

         5.Na(s) dissolves in the liquid mercury to form an amalgam, which is removed to the decomposer.

         6.In the decomposer the amalgam reacts with water to form sodium hydroxide, hydrogen gas and mercury.

                                              2Na/Hg + 2H2O(l) = 2Na+   +  2OH-  +  2Hg (l) 

 7. Sodium hydroxide solution and hydrogen gas are collected.

Disease State

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Q 1. What is COPD?

       Answer: CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) is an umbrella term used to describe progressive lung diseases including emphysema, chronic bronchitis, refractory (non-reversible) asthma, and some forms of bronchiectasis. This disease is characterized by increasing breathlessness.

      Emphysema occurs when the tiny air sacs in your lungs — the alveoli — break down and become larger. With the destruction of the alveoli, your lungs are less able to get oxygen out of the air and less effective at getting rid of carbon dioxide. The walls of the damaged air sacs are stretched and less flexible, so that air is trapped inside the lungs. When this happens the airways can become "flabby," and don't push out air as well. And because so much air is trapped in the lungs, your diaphragm (the muscle at the bottom of the lungs that acts like an accordion) can become shortened and unable to assist in breathing. Damaged air sacs trap air inside your lungs. You might feel that it's hard to take a deep breath. Like old balloons, the tiny air sacs get stretched out of shape and break down. Old air gets trapped inside the air sacs so there is no room for new air to get in.

    Chronic bronchitis is an inflammation of the airways. It results in coughing (with phlegm) that you have every day, and that occurs often. The inflammation occurs when the tiny hair-like projections — called cilia — that line your bronchial tubes are damaged. Normal cilia help propel mucus up the bronchial tubes. But when cilia are damaged, it becomes harder to cough up mucus, which in turn causes more coughing, more irritation, and more mucus production. And that means your airways become swollen and clogged. The result is obstruction and increased shortness of breath. You might say you have a "smoker's cough" or a cold that won't go away. But it could be due to damaged airways that have gotten tight, swollen, and filled with mucus. These changes limit airflow in and out of your lungs. And, this makes it hard to breathe.

Q 2. What is the signs and symtomps of COPD?

       Answer: Symptoms of COPD can be different for each person, but the common symptoms are:

• Shortness of breath*
• Frequent coughing (with and without sputum or phlegm)
• Increased breathlessness
• Feeling tired, especially when exercising or doing daily activities
• Wheezing
• Tightness in the chest.

Q 3. What are the causes of COPD?

     Answer: 

The causes are:

 

      1. Long-term exposure to lung irritants that damage the lungs and the airways usually is the cause of COPD.

      2.  Cigarette smoking

     3. Breathing in secondhand smoke, air pollution; or chemical fumes or dusts from the environment or workplace also can contribute to COPD.

     4. Rarely, a genetic condition called alpha-1 antitrypsin deficiency may play a role in causing COPD

Q 4. What are the diagnosis process?

      Answer:

• Pulmonary Function Tests

Pulmonary function tests measure how much air you can breathe in and out, how fast you can breathe air out, and how well your lungs deliver oxygen to your blood.

The main test for COPD is spirometry. Other lung function tests, such as a lung diffusion capacity test, also might be used. .

SPIROMETRY

During this painless test, a technician will ask you to take a deep breath in. Then, you'll blow as hard as you can into a tube connected to a small machine. The machine is called a spirometer.

The machine measures how much air you breathe out. It also measures how fast you can blow air out.

The image shows how spirometry is done. The patient takes a deep breath and blows as hard as possible into a tube connected to a spirometer. The spirometer measures the amount of air breathed out. It also measures how fast the air was blown out.

The test results also may help find out whether another condition, such as asthma or heart failure, is causing your symptoms.

• Other Tests

1. A chest x ray or chest CT scan. 
2. An arterial blood gas test. 

Treatment

COPD has no cure yet. However, lifestyle changes and treatments can help you feel better, stay more active, and slow the progress of the disease.

The goals of COPD treatment include:

• Relieving your symptoms
• Slowing the progress of the disease
• Improving your exercise tolerance or your ability to stay active
• Preventing and treating complications
• Improving your overall health

Types of medicines often prescribed for COPD:

• Bronchodilator

Bronchodilators relax the muscles around the airways which helps to keep them open and makes breathing easier. Most bronchodilators are often delivered through an inhaler or can be nebulized. 

Bronchodilators can be short-acting or long-acting. Short-acting bronchodilators work quickly so that you get relief from symptoms fast, but they wear off in a few hours. Long-acting bronchodilators provide relief for many hours, but the effect may be slower. Short- and long-acting bronchodilators include beta2-agonists and anticholinergics.

• Beta2-Agonists are very potent at relaxing tightened muscles around your airways. This opens the airway and makes breathing easier. Short-acting beta-agonists work within minutes but last only 4-6 hours. Long-acting beta-agonists may be slow to start working but can last up to 12 to 24 hours so are used to maintain open airways throughout the day or the night.
• Anticholinergics prevent the muscles around your airways from tightening so keep the airways open and help clear mucus from your lungs. This combination allows your cough to expel mucus more easily. There are short-acting and long-acting anticholinergics.

Beta-agonists and anticholinergics can be delivered through an inhaler or a nebulizer.

• Anti-Inflammatory

Decreasing inflammation leads to less swelling and mucus production in the airways and that makes it easier to breathe. These medicines are known as corticosteroids or steroids. They are usually inhaled with an inhaler device.

Corticosteroids can also be swallowed as a pill and are usually delivered for short periods of time in special circumstances when your symptoms are getting more severe. Steroids have serious side effects, such as weight gain, diabetes, osteoporosis, cataracts and increased risk of infection so they must be monitored carefully. Your doctor will talk with you about these side effects.

• Combination Medicines

A corticosteroid, an anticholinergic and a beta-agonist can be combined into one inhaler or nebulizer solution. The most common combinations contain two or three of these medicines as a:

• Short-acting beta-agonist and short-acting anticholinergic
• Long-acting beta-agonist and corticosteroid
• Long-acting anticholinergic and corticosteroid
• Long-acting beta-agonist and long-acting anticholinergic
• Long-acting beta-agonist, long-acting anticholinergic and corticosteroid
• 
  
• Antibiotics

People with COPD do experience flare-ups with more coughing, more mucus and more shortness of breath. This is often caused by bacterial or viral infections. Your doctor may give you an antibiotic to keep on hand and fill for when you have an infection.

Make sure you take all of the antibiotic exactly as prescribed.

• Vaccinations

COPD increases your risk for infection with influenza (flu) and pneumonia. Vaccines are available to protect you against the flu and you should get immunized every year. You need a yearly flu shot because the influenza virus changes slightly every year and you must get the latest and newest vaccine.

 Pneumococcal pneumonia is a bacterial infection of the lung that often follows an influenza infection. There are two vaccines to protect against this infection. You only need to get vaccinated once but you need to get each one. Your doctor can provide these to you.

Vaccinations are very important for people living with COPD to prevent COPD flare-ups so you can be healthy.

References Links:

• https://www.nhlbi.nih.gov/health-topics/copd
• http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd/diagnosing-and-treating/managing-your-copd-medications.html
• https://www.copdfoundation.org/What-is-COPD/Understanding-COPD/What-is-COPD.aspx

High Performance Liquid Chromatography

High Performance Liquid Chromatography

High Performance Liquid Chromatography (HPLC) is a form of column chromatography that pumps a sample mixture or analyte in a solvent (known as the mobile phase) at high pressure through a column with chromatographic packing material (stationary phase).

It is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of a mixture.

Fig: HPLC

Fig: HPLC process

               

Stationary phase: The substance on which adsorption of the analyte (the substance to be separated during chromatography) takes place. It can be a solid, a gel, or a solid liquid combination.

Mobile phase: Solvent which carries the analyte (a liquid or a gas). 

Types of HPLC

Based on the phase system (stationary) in the process:

Normal Phase HPLC

This method separates analytes on the basis of polarity. Stationary phase is polar (hydrophilic) and mobile phase is non-polar (hydrophobic).

Reverse Phase HPLC

It works on the principle of hydrophobic interactions hence the more non-polar the material is, the longer it will be retained. Stationary phase is non-polar (hydrophobic) and mobile phase is Polar (hydrophilic).

Size-exclusion HPLC

The column is filled with material having precisely controlled pore sizes, and the particles are separated according to their molecular size.

Ion-Exchange HPLC

The stationary phase has an ionically charged surface of opposite charge to the sample ions. This technique is used almost exclusively with ionic or ionizable samples.

Based on elution technique

1. Isocratic elution

  •A separation in which the mobile phase composition remains constant throughout the procedure is termed isocratic elution

   •In isocratic elution, peak width increases with retention time linearly with the number of theoretical plates. This leads to the disadvantage that late-eluting peaks get very flat and broad.

 • Best for simple separations

 • Often used in quality control applications that support and are in close proximity to a manufacturing process

2. Gradient elution

  •A separation in which the mobile phase composition is changed during the separation process is described as a gradient elution

  •Gradient elution decreases the retention of the later-eluting components so that they elute faster, giving narrower peaks. This also improves the peak shape and the peak height

  • Best for the analysis of complex samples

  • Often used in method development for unknown mixtures

  • Linear gradients are most popular

Principle

HPLC is a technique in analytic chemistry used to separate the components in a mixture, to identify each component and to quantify each component. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material. Each component in the sample interacts slightly different with the adsorbent material causing different flow rates for the different components and leading to the separation of the components as they flow out the column.

Instrumentation

1.      SOLVENT RESERVOIR

The reservoir that holds the mobile phase is called solvent reservoir.

The typical pore size used in a sinker frit (filter) is on the order of 5 - 10 microns; frits of smaller pore size are too likely to plug. In general, the mobile phase should be filtered through a 0.3 to 0.5-micron frit after the solvents and buffers are mixed in order to remove particulate matter.

HPLC instrument

2.      PUMP

The role of the pump is to force a liquid (called the mobile phase) through the liquid chromatograph at a specific flow rate, expressed in milliliters per min (mL/min). Normal flow rates in HPLC are in the 1-to 2-mL/min range. Typical pumps can reach pressures in the range of 6000-9000 psi (400-to 600-bar).

Types of HPLC Pumps:

a.      Reciprocating piston pumps:

Consists of a small motor driven piston which moves rapidly back and forth in a hydraulic chamber that may vary from 35-400μL in volume.

b.      Syringe type pump

These are most suitable for small bore columns because this pump delivers only a finite volume of mobile phase before it has to be refilled. These pumps have a volume between 250 to 500mL.

c.       Constant pressure pump

In these types of pumps, the mobile phase is driven through the column with the use of pressure from the gas cylinder. A low-pressure gas source is needed to generate high liquid pressures. The valving arrangement allows the rapid refill of the solvent chamber whose capacity is about 70mL.

3.      INJECTOR       

The injector serves to introduce the liquid sample into the flow stream of the mobile phase for analysis. It is equipped with six port valves so that a sample can be injected into the flow path at continuous pressure.

For a manual injector, the knob is manually operated to deliver the sample to the column. The knob is set to LOAD position for sample injection using a syringe, the sample is injected into the sample loop, which is separated from the flow path.

The knob is turned to INJECT position and the eluent travels through the loop from the pump and delivers the sample to the column.

Typical sample volumes for manual injector are 5-to 20-microliters (μL).

An autosampler is the automatic version for when the user has many samples to analyze or when manual injection is not practical. It can continuously inject variable volume of 1 μL-1mL.

4.      COLUMN

Column is considered the “heart of the chromatograph” the column’s stationary phase separates the sample components of interest using various physical and chemical parameters.

It is usually made of stainless steel to withstand high pressure caused by the pump to move the mobile phase through the column packing other material include PEEK and glass

The small particles inside the column are called the “packing” what cause the high back pressure at normal flow rates.

Column packing is usually silica gel because of its particle shape, surface properties, and pore structure give us a good separation.

Other material used include alumina, a polystyrene-divinyl benzene synthetic or an ion-exchange resin

Dimensions of the analytical column are usually -straight, Length (5 to 25 cm), diameter of column (3 to 5 mm), diameter of particle (35μm). Number (40 k to 70 k plates/m)

Guard column is used to remove particular matter and contamination, it protect the analytical column and contains similar packing its temperature is controlled at < 150 °C, 0.1 °C

5.      DETECTOR

Ultraviolet (UV)

This type of detector responds to substances that absorb light. UV detector is mainly to separate and identify the principal active components of a mixture. These are the most versatile, having the best sensitivity and linearity. UV detectors cannot be used for testing substances that are low in chromophores (colorless or virtually colorless) as they cannot absorb light at low range. They are cost-effective and popular and are widely used in industry.

Fluorescence

This is a specific detector that senses only those substances that emit light. This detector is popular for trace analysis in environmental science.

As it is very sensitive, its response is only linear over a relatively limited concentration range. As there are not many elements that fluoresce, samples must be syntesized to make them detectable.

Mass Spectrometry

The mass spectrometry detector coupled with HPLC is called HPLCMS. HPLC-MS is the most powerful detector, widely used in pharmaceutical laboratories and research and development.

The principal benefit of HPLC-MS is that it is capable of analyzing and providing molecular identity of a wide range of components.

Refractive Index (RI) Detection

The refractive index (RI) detector uses a monochromator and is one of the least sensitive liquid chromatography detectors. This detector is extremely useful for detecting those compounds that are non-ionic, do not absorb ultraviolet light and do not fluoresce e.g. sugar, alcohol, fatty acid and polymers.

6.      DATA COLLECTION DEVICE

Computer collects all the data from the detectors and gives the corresponding results.

Parameters

·         THEORETICAL

Theoretical parameters are largely derived from two sets of chromatographic theory: plate theory (as part of Partition chromatography), and the rate theory of chromatography / Van Deemter equation.

Retention time (tR ) 

Retention time is a measure of the time taken for a solute to pass through a chromatography column. It is calculated as the time from injection to detection. This is the sum of the total times the components spends in the mobile phase (t0) and in the stationary phase.

Retention (Capacity) Factor (k)

The retention (or capacity) factor (k) is a means of measuring the retention of an analyte on the chromatographic column.

It is the ratio of the time the component spends in the stationary phase to time in the mobile phase.

Determination of Retention factor

A high k value indicates that the sample is highly retained and has spent a significant amount of time interacting with the stationary phase.

Chromatographers like to keep k values between 1 and 10 for good separations.

Retention volume:

Retention volume is the volume of carrier gas required to elute 50% of the component from the column. It is the product of retention time and flow rate.

Retention volume = Retention time × flow rate

Resolution (Rs)

Resolution is the measure of extent of separation of 2 components and the base line separation achieved. A resolution value of 1.5 or greater between two peaks will ensure that the sample components are well (baseline) separated to a degree at which the area or height of each peak may be accurately measured.

Determination of Resolution

Selectivity (Separation) Factor (α)

The selectivity (or separation) factor (α) is the ability of the chromatographic system to ‘chemically’ distinguish between sample components. It is usually measured as a ratio of the retention (capacity) factors (k) of the neighboring two peaks

.

Determination of Separation factor 

The selectivity Factor (α) is always greater than one – as when α is equal to one, the two peaks are co-eluting (i.e. their retention factor values are identical). The greater the selectivity value, the further apart the apices of the two peaks become.

Efficiency

Efficiency factor practically measures how sharp component peaks on the chromatogram are. Efficiency factor is synonymous with plate number, and the 'number of theoretical plates'.

Efficiency of a column is expressed by the theoretical plates (N).

Determination of theoretical plates

If number of theoretical plates is high, the column is said to be highly efficient. In HPLC, high values like 40,000 to 70,000/meter are recommended.

Height Equivalent to a Theoretical Plate (HETP):

A theoretical plate is an imaginary or hypothetical unit of a column where distribution of solute between stationary phase and mobile phase has attained equilibrium. It can also be called as a functional unit of the column. A theoretical plate can be of any height, which describes the efficiency of separation. If HETP is less, the column is more efficient. If HETP is more, the column is less efficient.

HETP = length of the column/ no. of theoretical plates

Asymmetry factor:

A chromatographic peak should be symmetrical about its centre and said to follow Gaussian distribution. But in practice due to some factors, the peak is not symmetrical and shows tailing or fronting.

Fronting is due to saturation of stationary phase and can be avoided by using less quantity of sample.

Tailing is due to more active adsorption sites and can be eliminated by support pretreatment.

Determination of Asymmetry factor 

Asymmetry factor (0.95 to 1.05) can be calculated by

As = B/A (B, A calculated by 5% or 10% of the peak height).

Broad peaks occur due to the more conc. Of sample, large injection volume, column deterioration.

Ghost peaks occur due to the contamination of the column, compound from earlier injections.

Negative peaks occur if mobile phase absorbance is larger than sample absorbance.

Peak doubling occurs due to the co- elution of interfering compound, column over load, channeling in column.

Base line spikes occur due to the air bubbles in the mobile phase and/or detector, column deterioration.

·         INTERNAL DIAMETER

The internal diameter (ID) of an HPLC column is an important parameter that influences the detection sensitivity and separation selectivity in gradient elution. It also determines the quantity of analyte that can be loaded onto the column.

·         PARTICLE SIZE

Most traditional HPLC is performed with the stationary phase attached to the outside of small spherical silica particles (very small beads). These particles come in a variety of sizes with 5 µm beads being the most common. Smaller particles generally provide more surface area and better separations.

·         PORE SIZE

Many stationary phases are porous to provide greater surface area. Small pores provide greater surface area while larger pore size has better kinetics, especially for larger analytes. For example, a protein which is only slightly smaller than a pore might enter the pore but does not easily leave once inside.

·         PUMP PRESSURE

Pumps vary in pressure capacity, but their performance is measured on their ability to yield a consistent and reproducible volumetric flow rate. Pressure may reach as high as 60 MPa (6000 lbf/in²), or about 600 atmospheres. Modern HPLC systems have been improved to work at much higher pressures, and therefore are able to use much smaller particle sizes in the columns (<2 μm). These ultra-high performance liquid chromatography" systems or UHPLCs can work at up to 120 MPa (17,405 lbf/in²), or about 1200 atmospheres.

·         DETECTORS

HPLC detectors fall into two main categories: universal or selective. Universal detectors typically measure a bulk property (e.g. refractive index) by measuring a difference of a physical property between the mobile phase and mobile phase with solute while selective detectors measure a solute property (e.g. UV-Vis absorbance) by simply responding to the physical or chemical property of the solute.

·         Autosamplers

Large numbers of samples can be automatically injected onto an HPLC system, by the use of HPLC autosamplers. In addition, HPLC autosamplers have an injection volume and technique which is exactly the same for each injection, consequently they provide a high degree of injection volume precision.

Application

Pharmaceutical applications

1.                  To control drug stability.

2.                  Tablet dissolution study of pharmaceutical dosages form.

3.                  Pharmaceutical quality control.

4.                  Shelf life determinations of pharmaceutical products.

5.                  Identification of counterfeit drug products.

Environmental applications

1.         Phenols in Drinking Water.

2.      Identification of diphenhydramine in sediment samples.

3.      Biomonitering of PAH pollution in high-altitude mountain lakes through the analysis of fish bile.

4.      Estrogens in coastal waters - The sewage source.

5.      Toxicity of tetracyclines and tetracycline degradation products to environmentally relevant bacteria.

6.      Assessment of TNT toxicity in sediment.

Forensic applications

1.      A mobile HPLC apparatus at dance parties - on-site identification and quantification of the drug Ecstasy.

2.      Identification of anabolic steroids in serum, urine, sweat and hair.

3.      Forensic analysis of textile dyes.

4.      Determination of cocaine and metabolites in meconium.

5.      Simultaneous quantification of psychotherapeutic drugs in human plasma.

Clinical applications

1.      Quantification of DEET in Human Urine.

2.      Analysis of antibiotics.

3.      Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis.

4.      Detection of endogenous neuropeptides in brain extracellular fluids.

Food and Flavor

1.      Ensuring soft drink consistency and quality.

2.      Analysis of vicinal diketones in beer.

3.      Sugar analysis in fruit juices.

4.      Polycyclic aromatic hydrocarbons in Brazilian vegetables and fruits.

5.      Trace analysis of military high explosives in agricultural crops.

6.      Stability of aspartame in the presence of glucose and vanillin.

Advantages of HPLC

1.      Separations fast and efficient (high resolution power)

2.      Continuous monitoring of the column effluent

3.      It can be applied to the separation and analysis of very complex mixtures

4.      Accurate quantitative measurements.

5.      Repetitive and reproducible analysis using the same column.

6.      Adsorption, partition, ion exchange and exclusion column separations are excellently made.

7.      HPLC is more versatile than GLC in some respects, because it has the advantage of not being restricted to volatile and thermally stable solute and the choice of mobile and stationary phases is much wider in HPLC.

8.      Both aqueous and non-aqueous samples can be analyzed with little or no sample pretreatment.

9.      A variety of solvents and column packing are available, providing a high degree of selectivity for specific analyses.

10.  It provides a means for determination of multiple components in a single analysis.