Career Links
Abbott:
http://www.abbott.com/global/url/content/en_US/50:50/general_content/General_Content_00013.htm
Novartis:
http://www.novartis.com/careers/index.shtml
Sanofi Aventis:
http://en.sanofi-aventis.com/hr/hr.asp
Astra Zeneca:
http://www.astrazeneca.com/Careers
Merck:
http://www.merck.com/careers/
Wednesday, April 27, 2011
Find Job Opportunities in Pharmaceutical Companies
Career Links
Pfizer:
http://www.pfizer.com/careers/
GSK:
http://www.gsk.com/careers/index.htm
Bristol Myers Squibb:
http://www.bms.com/careers/Pages/home.aspx
Johnson & Johnson:
http://careers.jnj.com/home
Hoffman La-Roche
http://www.roche.com/home/careers.htm
Pfizer:
http://www.pfizer.com/careers/
GSK:
http://www.gsk.com/careers/index.htm
Bristol Myers Squibb:
http://www.bms.com/careers/Pages/home.aspx
Johnson & Johnson:
http://careers.jnj.com/home
Hoffman La-Roche
http://www.roche.com/home/careers.htm
Crystallization
Definition:
It is the (natural or artificial) process of formation of solid crystals precipitating from a solution, melt or more rarely deposited directly from a gas.
Crystallization is also a chemical solid-liquid separation technique in which mass transfer of a solute from the liquid solution to a pure solid crystalline phase occurs.
Process of crystallization:
There are two major events in the process of crystallization
a. Nucleation
b. Crystal growth
Nucleation:
A step where the solute molecules dispersed in the solvent start together into clusters on the nanometer scale. These become stable under the current operating conditions.
However, when the slucters are not stable they redissolve. Therefore, the clusters need to reach a critical size in order to become stable nuclei.
It is at the stage of nucleation that the atoms arrange in a defined and periodic manner that defines the crystal growth.
Crystal growth:
It is the subsequent growth of the nuclei that succeed in achieving the critical cluster size.
Supersaturation:
Nucleation and crystal growth continue to occur simultaneously while the supersaturation exists.
Supersaturation is the driving force of the crystallization hence the rate of nucleation and growth is driven by the existing supersaturation in the solution.
Once the supersaturation is exhausted, the solid-liquid system reaches equilibrium and the crystallization is complete.
Polymorphism:
Many compounds have the ability to crystallize with different crystal structures a phenomenon called polymorphism.
Each polymorph is in fact a different thermodynamic solid state crystal polymorphs of the same compound exhibit different physical properties such as dissolution rate, shape and melting point etc.
So, polymorphism is of major importance in industrial manufacture of crystalline product.
Artificial method for crystallization:
For crystallization to occur from a solution, it must be supersaturated. This can be achieved by solution cooling, addition of a second solvent to reduce the solubility of the solute (techniques known as antisolvent or drawn out), chemical reaction or change in pH being the most common methods used in industrial practice.
Other methods such as solvent evaporation can also be used.
Applications:
Crystal production such as powdered slat for food industry, silicon crystal wafer production and production of sucrose from sugar beet, where the sucrose is crystallized out from an aquous solution.
Purification:
Crystallization separates out a product from a liquid (feedstream) often in extremely pure form by cooling the feedstream or adding precipitants which lower the solubility of the desired product so that it forms crystals.
Well formed crystals are expected to be pure because each molecule or ion must fit perfectly into the crystal as it leaves the solution.
Apparatus for crystallization:
Tank crystallizers:
Saturated solutions are allowed to cool in open tanks. After a period of time the mother liquid is drained and the crystals removed. In this method, nucleation and size of crystal are difficult to control. Labor costs are high.
Scrapped surface crystallizers:
One type of scraped surface crystallizer consists of Swensen-Walker crystallizer consisting an open of an open trough 0.6 meter wide with a semicircular bottom having a cooling jacket outside.
A slow speed spiral agitator rotates and suspends the growing crystals on turning the blades pass close to the walls and break off any deposits or crystals on the cooled wall.
It is the (natural or artificial) process of formation of solid crystals precipitating from a solution, melt or more rarely deposited directly from a gas.
Crystallization is also a chemical solid-liquid separation technique in which mass transfer of a solute from the liquid solution to a pure solid crystalline phase occurs.
Process of crystallization:
There are two major events in the process of crystallization
a. Nucleation
b. Crystal growth
Nucleation:
A step where the solute molecules dispersed in the solvent start together into clusters on the nanometer scale. These become stable under the current operating conditions.
However, when the slucters are not stable they redissolve. Therefore, the clusters need to reach a critical size in order to become stable nuclei.
It is at the stage of nucleation that the atoms arrange in a defined and periodic manner that defines the crystal growth.
Crystal growth:
It is the subsequent growth of the nuclei that succeed in achieving the critical cluster size.
Supersaturation:
Nucleation and crystal growth continue to occur simultaneously while the supersaturation exists.
Supersaturation is the driving force of the crystallization hence the rate of nucleation and growth is driven by the existing supersaturation in the solution.
Once the supersaturation is exhausted, the solid-liquid system reaches equilibrium and the crystallization is complete.
Polymorphism:
Many compounds have the ability to crystallize with different crystal structures a phenomenon called polymorphism.
Each polymorph is in fact a different thermodynamic solid state crystal polymorphs of the same compound exhibit different physical properties such as dissolution rate, shape and melting point etc.
So, polymorphism is of major importance in industrial manufacture of crystalline product.
Artificial method for crystallization:
For crystallization to occur from a solution, it must be supersaturated. This can be achieved by solution cooling, addition of a second solvent to reduce the solubility of the solute (techniques known as antisolvent or drawn out), chemical reaction or change in pH being the most common methods used in industrial practice.
Other methods such as solvent evaporation can also be used.
Applications:
Crystal production such as powdered slat for food industry, silicon crystal wafer production and production of sucrose from sugar beet, where the sucrose is crystallized out from an aquous solution.
Purification:
Crystallization separates out a product from a liquid (feedstream) often in extremely pure form by cooling the feedstream or adding precipitants which lower the solubility of the desired product so that it forms crystals.
Well formed crystals are expected to be pure because each molecule or ion must fit perfectly into the crystal as it leaves the solution.
Apparatus for crystallization:
Tank crystallizers:
Saturated solutions are allowed to cool in open tanks. After a period of time the mother liquid is drained and the crystals removed. In this method, nucleation and size of crystal are difficult to control. Labor costs are high.
Scrapped surface crystallizers:
One type of scraped surface crystallizer consists of Swensen-Walker crystallizer consisting an open of an open trough 0.6 meter wide with a semicircular bottom having a cooling jacket outside.
A slow speed spiral agitator rotates and suspends the growing crystals on turning the blades pass close to the walls and break off any deposits or crystals on the cooled wall.
Adsorption
Definition:
“it is a phenomenon in which accumulation of a substance at the boundary on interface between the hetergenous phases takes place.”
Explanation:
It is difficult from absorption, as the absorption is the distribution of a substance throuth the bulk solution while adsorption is a surface phenomenon.
Sorption:
It is sometimes very difficult to define clearly the interface of highly porous solids, so for these system the term sorption is used as we cannot distinguish wether it is adsorption or absorption.
The substance that is attached to the surface of the solid is called adsorbate and the surface on which it gets adsorption is called adsorbent.
Occurance:
Adsorption can occur on following interfaces:
• Solid/Liquid
• Solid/gas
• Liquid/gas
• Liquid/liquid
Since adsorption is a surface phenomenon. The most effective adsorption are those with high surface area e.g. finely divided solids.
Positive adsorption:
Adsorption shows the ratio of a substance at the interface and the bulk phase if the concentration of the substance at the interface is greater. Than the concentration of the substance in bulk phase then it is called as positive adsorption.
Negative adsorption:
If the volume concentration of substance is higher than the concentration of bulk is known as negative adsorption.
Types of adsorption:
There are two types of adsorption:
Physical adsorption
Negative adsorption
1. Physical adsorption:
In physical adsorption the adsorbate is attached with adsorbent by Vander Waals or Electrostatic weak forces and it is characterized by low heat of adsorption.
Physical adsorption of gases is common at low temperature and high pressure. The gas in the adsorbent layer is in equilibrium with the gas molecule. In the bulk gas the equilibrium depends upon the nature of the adsorbent.
2. Chemical adsorption:
This involves the chemical combination of adsorbate at the surface of adsorbent. It is characterized by high heat of adsorption and unlike physical adsorption is irreversible. In many cases the chemical adsorption is slow because the molecule has to acquire an energy of interaction before they can react with the adsorbent, the rate of uptake will increase with increase of temperature.
Factors affecting the adsorption:
Solubility of adsorbate:
The adsorption is inversely proportional to the solubility of the adsorbate in the adsorbent.
Adsorption α 1/Solubility
pH:
it does not effect the adsorption directly pH of the solution affect the degree of ionization.
Usually the drug with a single molecule has more adsorption.
Nature of the adsorption:
Nature of the adsorbent have major effect on the adsorption by increasing the surface area, the adsorption rate could be increased. It can be increased by making it porous or finely divided.
Temperature:
Adsorption is an Exothermic process so increase in temperature will decrease. The adsorption and vice versa.
Pressure:
Adsorbed amount of adsorbate is directly proportional to the pressure applied.
“it is a phenomenon in which accumulation of a substance at the boundary on interface between the hetergenous phases takes place.”
Explanation:
It is difficult from absorption, as the absorption is the distribution of a substance throuth the bulk solution while adsorption is a surface phenomenon.
Sorption:
It is sometimes very difficult to define clearly the interface of highly porous solids, so for these system the term sorption is used as we cannot distinguish wether it is adsorption or absorption.
The substance that is attached to the surface of the solid is called adsorbate and the surface on which it gets adsorption is called adsorbent.
Occurance:
Adsorption can occur on following interfaces:
• Solid/Liquid
• Solid/gas
• Liquid/gas
• Liquid/liquid
Since adsorption is a surface phenomenon. The most effective adsorption are those with high surface area e.g. finely divided solids.
Positive adsorption:
Adsorption shows the ratio of a substance at the interface and the bulk phase if the concentration of the substance at the interface is greater. Than the concentration of the substance in bulk phase then it is called as positive adsorption.
Negative adsorption:
If the volume concentration of substance is higher than the concentration of bulk is known as negative adsorption.
Types of adsorption:
There are two types of adsorption:
Physical adsorption
Negative adsorption
1. Physical adsorption:
In physical adsorption the adsorbate is attached with adsorbent by Vander Waals or Electrostatic weak forces and it is characterized by low heat of adsorption.
Physical adsorption of gases is common at low temperature and high pressure. The gas in the adsorbent layer is in equilibrium with the gas molecule. In the bulk gas the equilibrium depends upon the nature of the adsorbent.
2. Chemical adsorption:
This involves the chemical combination of adsorbate at the surface of adsorbent. It is characterized by high heat of adsorption and unlike physical adsorption is irreversible. In many cases the chemical adsorption is slow because the molecule has to acquire an energy of interaction before they can react with the adsorbent, the rate of uptake will increase with increase of temperature.
Factors affecting the adsorption:
Solubility of adsorbate:
The adsorption is inversely proportional to the solubility of the adsorbate in the adsorbent.
Adsorption α 1/Solubility
pH:
it does not effect the adsorption directly pH of the solution affect the degree of ionization.
Usually the drug with a single molecule has more adsorption.
Nature of the adsorption:
Nature of the adsorbent have major effect on the adsorption by increasing the surface area, the adsorption rate could be increased. It can be increased by making it porous or finely divided.
Temperature:
Adsorption is an Exothermic process so increase in temperature will decrease. The adsorption and vice versa.
Pressure:
Adsorbed amount of adsorbate is directly proportional to the pressure applied.
Monday, April 25, 2011
Loop Diuretics (Some Questions)
Q:1. Why loop diuretics are often called as high ceiling diuretics?
Ans: They are often called as high ceiling diuretics because they are highly effective in inhibition of coupled transport of Na+/K+/2Cl- through luminal membrane of thick ascending limb of Henle’s loop as ascending limb results in reabsorption of 20-30 percent of NaCl which has already been filtered.
Q:2. Compare loop diuretics and thiazide diuretics.
Ans:
Differences between loop diuretics and thiazide diuretics:
1. Loop diuretics are more effective than thiazide diuretics.
2. The onset of action and duration of action of loop diuretics is shorter than the thiazide diuretics.
3. Loop diuretics show efficacy even in the presence of electrolyte and acid base disturbance unlike thiazide siuretics.
4. Loop diuretics are not good than thiazide diuretics against uncomplicated mild to moderate hypertension.
5. Loop diuretics increase renal blood flow whereas thiazide diuretics have the ability of lessening renal flow of blood.
6. Loop diuretics tend to increase Ca2+ in urine whereas thiazide diuretics cause a decrease in Ca2+ in urine.
Similarities between loop diuretics and thiazide diuretics:
1. They have almost identical side effects.
Ans: They are often called as high ceiling diuretics because they are highly effective in inhibition of coupled transport of Na+/K+/2Cl- through luminal membrane of thick ascending limb of Henle’s loop as ascending limb results in reabsorption of 20-30 percent of NaCl which has already been filtered.
Q:2. Compare loop diuretics and thiazide diuretics.
Ans:
Differences between loop diuretics and thiazide diuretics:
1. Loop diuretics are more effective than thiazide diuretics.
2. The onset of action and duration of action of loop diuretics is shorter than the thiazide diuretics.
3. Loop diuretics show efficacy even in the presence of electrolyte and acid base disturbance unlike thiazide siuretics.
4. Loop diuretics are not good than thiazide diuretics against uncomplicated mild to moderate hypertension.
5. Loop diuretics increase renal blood flow whereas thiazide diuretics have the ability of lessening renal flow of blood.
6. Loop diuretics tend to increase Ca2+ in urine whereas thiazide diuretics cause a decrease in Ca2+ in urine.
Similarities between loop diuretics and thiazide diuretics:
1. They have almost identical side effects.
Loop diuretics
These diuretics act on the medullary and cortical (thick) ascending limb of Henle’s loop, although to some extent they also act on the proximal and distal tubules. They are more effective than thiazide diuretics.
Mechanism of action:
They inhibit Na+/K+/2Cl- symport on luminal membrane of thick ascending limb of Henle’s loop causes
a. Decreased reabsorption of NaCl
b. Lessen the normal lumen positive potential that derives from K+ recycling resulting in increased excretion of Mg2+ and Ca2+
They tend to decrease renal vascular resistance and resulting in increased renal blood flow.
They also promote prostaglandin synthesis. Prostaglandins also have some role as diuretic.
They produce large amount of urine.
1. Acute pulmonary edema of heart failure
2. Acute pulmonary edema (When given IV)
3. Impaired renal function
4. Hypercalcemia
They causes an increased tub ular Ca2+ excretion.
5. Hyperkalemia
6. Increased intracranial pressure
7. Diabetic nephropathy
8. Hypertensive situations
Pharmacokinetics:
They have short duration of action of approximately 2-4.5 hours. They are eliminated by glomerular filtration and tubular secretion. Their half life depends on the renal function. They are excreted through urine.
Adverse effects:
They have almost similar adverse effects as those of thiazide diuretics. But they may cause severe electrolytic imbalances and water depletion.
• Hypersensitivity reactions:
Skin rash, interstitial nephritis
• Water, electrolytes and acid-base balance:
Voiding of extra water, Hypercalcemia, hyponatremia, Hypomagnesemia,
Hypokalemic metabolic alkalosis:
More Na+ at the collecting tubule results in more K+ exchange with Na+ in the tubule. This results in hypokalemia.
More K+ loss results in more H+, resulting in hypokalemic alkalosis.
This can be reduced by the use of potassium sparing diuretics or potassium rich foods.
• Blood:
Transient granulocytopenia and thrombocytopenia
• Muscles:
Severe pain and tenderness in patients with renal failure
• Miscellaneous:
Ototoxicity:
Affect on hearing.
Hyperuricemia:
Blocks secretion of uric acid by competitively working at renal and biliary secretary systems. This results in gouty attacks.
Acute hypovolemia:
They cause a reduction in blood volume. This results in hypotension, shock and cardiac arrhythmias.
Contraindications:
It is contraindicated in patients with hepatic coma, hypokalemia, hypotension and hypersensitivity to sulfonamides.
Interaction:
Indomethacin interferes with the production of prostaglandin synthesis, so that is why causes some inhibitory effects on diuretic action of loop diuretics.
Mechanism of action:
They inhibit Na+/K+/2Cl- symport on luminal membrane of thick ascending limb of Henle’s loop causes
a. Decreased reabsorption of NaCl
b. Lessen the normal lumen positive potential that derives from K+ recycling resulting in increased excretion of Mg2+ and Ca2+
They also promote prostaglandin synthesis. Prostaglandins also have some role as diuretic.
Therapeutic uses:
They produce large amount of urine.
1. Acute pulmonary edema of heart failure
2. Acute pulmonary edema (When given IV)
3. Impaired renal function
4. Hypercalcemia
They causes an increased tub ular Ca2+ excretion.
5. Hyperkalemia
6. Increased intracranial pressure
7. Diabetic nephropathy
8. Hypertensive situations
Pharmacokinetics:
They have short duration of action of approximately 2-4.5 hours. They are eliminated by glomerular filtration and tubular secretion. Their half life depends on the renal function. They are excreted through urine.
Adverse effects:
They have almost similar adverse effects as those of thiazide diuretics. But they may cause severe electrolytic imbalances and water depletion.
• Hypersensitivity reactions:
Skin rash, interstitial nephritis
• Water, electrolytes and acid-base balance:
Voiding of extra water, Hypercalcemia, hyponatremia, Hypomagnesemia,
Hypokalemic metabolic alkalosis:
More Na+ at the collecting tubule results in more K+ exchange with Na+ in the tubule. This results in hypokalemia.
More K+ loss results in more H+, resulting in hypokalemic alkalosis.
This can be reduced by the use of potassium sparing diuretics or potassium rich foods.
• Blood:
Transient granulocytopenia and thrombocytopenia
• Muscles:
Severe pain and tenderness in patients with renal failure
• Miscellaneous:
Ototoxicity:
Affect on hearing.
Hyperuricemia:
Blocks secretion of uric acid by competitively working at renal and biliary secretary systems. This results in gouty attacks.
Acute hypovolemia:
They cause a reduction in blood volume. This results in hypotension, shock and cardiac arrhythmias.
Contraindications:
It is contraindicated in patients with hepatic coma, hypokalemia, hypotension and hypersensitivity to sulfonamides.
Interaction:
Indomethacin interferes with the production of prostaglandin synthesis, so that is why causes some inhibitory effects on diuretic action of loop diuretics.
Chlorothiazides
Chlorothiazed is the prototype of thiazide diuretics. This is used widely, orally effective and well tolerated.
They are effective in edema of hepatic cirrhosis and heart failure.
Pharmacokinetics:
Onset of action is 2 hours after oral administration and 10-15 minutes after IV administration. Its duration of action is about 4-12 hours.
They are effective in edema of hepatic cirrhosis and heart failure.
Pharmacokinetics:
Onset of action is 2 hours after oral administration and 10-15 minutes after IV administration. Its duration of action is about 4-12 hours.
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