Ideally, an impurity profile should show all impurities in a single format to allow monitoring of any variation in the profile.
The driving forces for studying an impurity profile are quality considerations and regulatory requirements.
Samples to be profiled
. Impurity profiling should be done for APIs, process check of the synthesis or formulation, and final drug product.
Components in an impurity profile.
Ideally, an impurity profile should show synthesis-related impurities, formulation-related impurities, degradation products,
and interaction products.
Crucial factors for controlling impurities in API
s. Several factors are important in controlling impurities in APIs as further outlined.
. The size of crystals not only determines the quality, but also the stability of the drug. During crystallization, fine
crystals should be formed to prevent entrapment of minute amounts of chemicals from the mother liquor, which in turn causes
degradation of the drug.
Many unwanted chemicals, including residual solvents, could be removed by thorough washing of the wet cake, which if not
done correctly, could lead to retention of solvents and impurities in the cake.
Use of vacuum dryer or a fluid-bed dryer is always advisable in comparison to a tray dryer. Use of the former reduces drying
time and brings about uniform drying, which is helpful in drying sensitive drug substances.
The packing of bulk drugs should be based upon their nature and sensitivity. Light-sensitive products should be packed in
light protective packing. Use of opaque containers for ciprofloxacin eye-drops preparations protects the active ingredients
from photodegradation (22). Use of ampuls with either black carbon paper or aluminum foil for ergometrine produced negligible
degradation (40). It is important to determine the most appropriate container-closure system.
Production methods based on stability studies
. A manufacturer of a bulk drug should perform a detailed investigation of the process, including stability studies while
finalizing the method of preparation. For example, for producing diclofenac sodium injections, the aseptic filtration process
is better than the autoclave method that produces the impurity (16).
Measures by pharmacopoeias
. Pharmacopoeias should take steps to incorporate impurity limits for drug substances made from a raw material in which that
particular impurity is controlled. It becomes convenient for the users if the impurity limit is mentioned in the dosage forms.
Parts I, II, and III of this article discussed the types, origin, causes, chemistry, and impact of impurities in APIs and
drug products (1, 2). Parts I and II explained how, when, and why impurities are formed. This article, Part III, highlighted
the degradation-related, formulation-related, and metabolite impurities, the various analytical techniques available for their
identification and separation, and crucial factors that are to be controlled while preparing bulk drugs.
Kashyap R. Wadekar , PhD ,* is a research scientist (II), Ponnaiah Ravi , PhD , is senior vice-president of R&D, Mitali Bhalme , PhD , is an associate research scientist, S. Srinivasa Rao is a research associate, K. Vigneshwar Reddy is a research associate, L. Sampath Kumar is a research chemist, and E. Balasubrahmanyam is a research chemist, all with Neuland Laboratories, 204 Meridian Plaza, 6-3-854/1, Ameerpet, Hyderabad, India, tel. 91
40 30211600, email@example.com
*To whom all correspondence should be addressed.
Submitted: Sept. 19, 2011; Accepted Nov. 28, 2011.