15. Sources of Impurities
Department of Pharmaceutical Chemistry
d) Equipment / Reaction vessels used in the process of manufacturing:-
• Equipment's or reactions vessels employed in the manufacturing process are made of
glass, tube, metals or their alloys.
• The material of the equipment may react with the reagents and solvents used in the
process of manufacturing and contribute to impurities in the end product.
• In order to control the impurities arising from chemical reactions between the solvents,
reagents or both with the reaction vessel, vessel made from hard inert glass like pyrex –
borosilicate glass should be used. However, its high cost limits its use.
17. Sources of Impurities
Department of Pharmaceutical Chemistry
Example:
Potassium iodide is synthesized from kelp (ash of a sea weed). When sea weed containing
nitrogenous organic matter is heated at very high temperature in the presence of alkali,
cyanides are generated. These cyanides may get incorporated as an impurity.
19. Sources of Impurities
Department of Pharmaceutical Chemistry
Example:
Synthesis of calcium chloride involves addition of pure calcium carbonate to slightly
excess quantity of dilute hydrochloric acid with continuous stirring followed by filtration
and concentration of filtrate to give CaCl2 crystals.
If the ingredients are not mixed properly or if any amount of HCl passes through
the filter or if the concentration is not properly carried out, then it affects the final product.
CaCO3 + 2HCl CaCl2 + H2O + CO2
21. Sources of Impurities
Department of Pharmaceutical Chemistry
Even in a well run manufacturing house, certain hazards exist which leads to product contamination.
23. Sources of Impurities
Department of Pharmaceutical Chemistry
Particulate Contamination:-
Example-
• Eye ointments packed in metal tubes made up of tin, aluminium generally get contaminated
due to the extrusion of metal particles from the packing material.
• The extent of contamination depends upon the viscosity of the ointment.
• As the viscosity of the ointment increases, the extent of extrusion increases.
Process Errors:-
• Minor errors are undesirable, but they are probably of serious concern in the case of solutions
of potent medicaments.
• The preparation of such solutions, therefore calls for special precautions such as filtration to
avoid the danger of undissolved solute contaminating part of the batch.
• Failure to acknowledge the mechanical efficiency of mixing, filling, tabletting, sterilising &
other equipment can lead to minor variation.
• Mixing powders of significantly different particle size or density needs special care.
• Special care is essential to avoid mixing & filling errors in the preparation of low dosage form
(< or = 5mg) such as tablets & capsules of highly potent medicaments.
25. Sources of Impurities
Department of Pharmaceutical Chemistry
Microbial Contamination:-
Almost all the pharmaceutical preparations may undergo microbial contamination during
the process of manufacture or during storage. Generally raw materials obtained naturally are
more prone to microbial contamination. Therefore to control it, sterility tests should be
performed on all the products, mainly upon liquids or creams applied on the mucous
membranes or broken skin, ophthalmic and parenteral preparations.
