Phase purity of active pharmaceutical ingredients (API) affects a range of physical, chemical and biological properties such as dissolution rate, stability and bioavailability. The pharmaceutical industry has frequently recourse the milling, shifting and drying which causes the impacts on phase of products. The different phases of products known as polymorphism and has become the challenge in pharmaceutical industry, in order to meet the specific polymorph of an individual product with respect to its quality specification. Pharmaceutical solids often exhibit polymorphism, which leads to different physiological properties; therefore, the understanding of manufacturing and control of polymorphic forms are essential aspects for product development and regulatory compliances in the pharmaceutical industry. X-ray powder diffraction (XRPD) is generally used for the characterization of polymorphism. XRPD method provides an advantage over other means of analysis in that it is usually non-destructive nature. XRPD investigations can also be carried out under in situ conditions and specimens exposed to non-ambient conditions such as low or high temperature and humidity.
Cite this article:
R.C. Pantola, Rakesh Bahuguna. Polymorphism: Quality rationalization, mitigation and authentication strategies with respect to regulatory compliances in pharmaceutical industry. Research J. Pharm. and Tech. 5(10): October 2012; Page 1264-1269.
1 Phoenix K and Andrews J. Adopting a Risk - Based Approach to 21
CFR Part 11 Assessments, Pharmaceutical Engineering. 2003:23-4.
2 Corradini P. X-ray studies of conformation: observation of
different geometries of the same molecule. Chem. Ind. (Milan) 1973: 55:
3 Haleblian JK and McCrone WC. Pharmaceutical applications of
polymorphism. J. Pharm. Sci. 1969:58: 911-929.
4 Haleblian JK. Characterization of habits and crystalline
modifications of solids and their pharmaceutical applications. J. Pharm. Sci.
1975: 64: 1269-1288.
5 Michael L. Pharmaceutical process
DA, Serajuddin ATM and Jacobson H. "Preformulation testing." In HA
Lieberman, L Lachman, and JB Schwartz (eds.) Pharmaceutical Dosage Forms:
Tablets (Vol. 1). Marcel Dekker, Inc., New York, 1989,
7 Guidance for industry ANDAs. Centre for
drug research Evluation and Research (CDER).2007.http:www.fda.gov./cder /guidance/index.htm.
8 Vippagunta SR, Brittain HG and Grant DJW. "Crystalline
solids," Adv. Drug Del. Rev. 2001:48:3-26.
HG and Fiese EF. Effect of
pharmaceutical processing on drug polymorphs and solvates. In H. G. Brittain
(ed.) Polymorphism in Pharmaceutical Solids. Marcel Dekker, Inc.1999 New York.
10 Sun C and Grant DJW. Influence of crystal structure on the
tableting properties of sulfamerazine polymorphs. Pharm. Res.2001: 18: 274-280.
11 Genck WJ. The effects of mixing on scale-up _ how crystallization
and precipitation React. Chem. Process.2000: 63: 47.
12 Beckmann W. Seeding the desired polymorph: background,
possibilities, imitations, and case studies. Org. Proc. Res. Dev.2000: 4:
13 Bernstein J. Polymorphism in Molecular Crystals. Oxford, UK:
Clarendon Press 2002.
14 Morris KR, Griesser UJ, Eckhardt CJ and Stowell JG. Theoretical
approaches to physical transformations of active pharmaceutical ingredients
during manufacturing processes. Adv. Drug Delivery Rev. 2001:48: 91-114.
15 Aguiar AJ, Krc J, Kinkel AW and Samyn JC. Effect of polymorphism
on the absorption of chloramphenicol from chloramphenicol palmitate. J Pharm
Sci 1967: 56: 847– 853.
16 Brittain HG. Polymorphism in Pharmaceutical Solids, Marcel Dekker,
New York, 1999.
17 Byrn SR, Pfeiffer RR, Stephenson G, Grant DJW and Gleason WB. Solid-state pharmaceutical
chemistry. Chem Mater 1994: 6: 1148–1158.
18 Byrn S, Pfeiffer R, Ganey M, Hoiberg C and Poochikian G. Pharmaceutical solids: a
strategic approach to regulatory considerations. Pharm Res 1995: 12: 945–954.
19 International Conference on Harmonization Q6A Guideline:
Specifications for New Drug Substances and Products: Chemical Substances,
20 Yu L X, Furness M S, Raw A, Woodland K P, Nashed N E, Ramos E,
Miller S P F, Adams R C, Fang F, Patel R M, Holcombe F O Jr, Chiu Yand Hussain
AS. Scientific considerations of pharmaceutical solid polymorphism in
abbreviated new drug applications. Pharm Res 2003: 20: 531– 536.