Studies on the Crystal Forms of Pefloxacin: Preparation, Characterization, and Dissolution Profile MANGE RAM YADAV, 1 ANWAR R. SHAIKH, 1 V. GANESAN, 1 RAJANI GIRIDHAR, 1 RENU CHADHA 2 1 Pharmacy Department, Faculty of Technology and Engineering, The M. S. University of Baroda, Baroda, Vadodara 390 001, India 2 University Institute of Pharmaceutical Sciences, Panjab University, Panjab, Chandigarh 160 014, India Received 25 April 2007; revised 8 July 2007; accepted 25 July 2007 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.21178 ABSTRACT: Different crystal forms of pefloxacin were prepared using solvents of varying polarity. X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermo- gravimetric analysis (TGA), infrared absorption spectroscopy (FT-IR), melting point, microcalorimetry and in vitro dissolution rate studies were conducted to investigate various characterstics of different crystalline forms of the pefloxacin. Five different polymorphs of pefloxacin have been identified on the basis of instrumental techniques. The polymorphs differed in their dissolution profile and all of them showed unusual behavior of highest dissolution in the first 15 min. The rate of dissolution went on decreasing and got stabilized to a constant value after 4 h. ß 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2637–2648, 2008 Keywords: polymorphism; preformulation; dissolution rate; calorimetry (DSC); FTIR; thermal analysis; X-ray powder diffractometry INTRODUCTION Polymorphism may be defined as the ability of a compound to exhibit different crystalline forms in which the molecule has different crystal lattice. 1 Because different polymorphs may exhibit sig- nificantly different pharmaceutically relevant properties, discovery and characterization of polymorphs are essential preformulation steps in pharmaceutical research and development. 2 Currently, one of the most widely used methods for preparation of polymorphs is recrystalization from different solvents. 3 Fluoroquinolones are broad spectrum antimicro- bials which are highly effective in the treatment of a wide variety of clinical infections. 4,5 Pefloxacin 1-ethyl-6-fluoro-7-(4-methylpiperazine)1-yl]-4-oxo- quinoline-3-carboxalic acid (Fig. 1), a fluoroquino- lone antibacterial agent, is active against various gram positive as well as gram negative micro- organisms. 6 In contrast to the numerous articles on fluoroquinolones such as the crystal structure of ofloxacin, 7 polymorphism of norfloxacin, 8 com- plexation of ciprofloxacin, 9,10 thermal behavior of norfloxacin 11 and dissolution studies on nor- floxacin, 12 literature on polymorphism of pefloxacin is not available to date. Dissolution is a critical parameter in the evaluation of pharmaceutical dosage forms for the development of in vitro–in vivo correlations and for quality control of desired product per- formance. 13 Also, bioavailability of a drug depends upon the rate of absorption of the drug from the gastrointestinal tract when given by oral route. Since a majority of drugs are absorbed in GIT by passive diffusion, dissolution rate of the drug in GIT is a regulating factor for the bioavailability of the drug. 14 Correspondence to: Mange Ram Yadav (Telephone: þ91- 265-2434187; Fax: þ91-265-2423898; E-mail: mryadav11@yahoo.co.in) Journal of Pharmaceutical Sciences, Vol. 97, 2637–2648 (2008) ß 2007 Wiley-Liss, Inc. and the American Pharmacists Association JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 97, NO. 7, JULY 2008 2637