Wednesday, 5 October 2011


Pyrogens in Pharmaceutical Products


Pyrogens are fever producing agents. They can cause febrile reactions when sufficient amounts enter in the circulatory system. Pyrogens are the metabolic products of microorganisms (bacteria,yeasts and moulds), chemically they are lipid substances associated with a carrier molecule, which is usually a polysaccharide. The carrier can also be a peptide. Bacterial endotoxin is the most significant pyrogen because of its potency and ubiquity.

All microbes produce pyrogen; the most potent pyrogen comes from gram-negative bacteria. Humans react to pyrogen with fever, chills, headache, increased blood pressure and a constellation of other symptoms.

Fever Inducing Mechanism
1.Pyrogens entering in the blood stream binds to lipopolysaccharide binding protein (LPB).
2.LPB takes it in to the recticuloendothelial system (RES).
3.The receptor cells in the RES are circulating mononuclear cells.
4.This attachment to the receptor cells induces the production of proinflammatory cytokines.
5.These cytokines are interleukin1 &6 and tumour necrosis factor. These factors produces inflammation and fever.

Pyrogens in Pharmaceutical Products
Pyrogens in large volume parenterals may make the patients very ill and the effect of rise of temperature may be fatal. Hence there is a need for testing parenteral solutions for their apyrogenesity and Pharmacopoeias make it compulsory. There can be several sources of pyrogens in parenteral products. Usual sources include the water (used as the vehicle),raw material inputs, Primary packing materials or equipment used in the preparation of the product.

Anything that is to be administered parenterally has to be sterile and apyrogenic. Apyrogenesity means lack of pyrogens.The  vehicle (usually water) used for parenteral preparation  may be sterilized  by autoclaving, which would kill the vegetative organisms as well as the spores. But the metabolic products of microorganisms may stay in the water. These products are not destroyed by autoclaving. Since they cannot be destroyed at the usual autoclaving temperature, they must be prevented from getting into water. So the water being taken for parenteral preparation must be apyrogenic.

Pharmaceutical manufacturers and compounding pharmacies prevent pyrogen contamination through the use of pyrogen-free raw materials and depyrogenated equipment.

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