• TAMIRIS A. JULIO LACFar, Institute of Chemistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil
  • JERUSA S. GARCIA LACFar, Institute of Chemistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil
  • RUDY BONFILIO EQFAR/NCQ, Faculty of Pharmaceutical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil
  • MAGALI B. D. E. ARAUJO EQFAR/NCQ, Faculty of Pharmaceutical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil
  • MARCELLO G. TREVISAN INCTBio, State University of Campinas, Campinas, São Paulo, Brazil


Moxifloxacin hydrochloride, Crystal form, Thermal Analysis, Non-thermal methods, Shake-Flask


Objective: This study aims to evaluate possible crystalline changes that can occur with MOX under the influence of temperature and relative humidity (RH) as well as to determine the relative solubility of the observed crystalline forms.

Methods: Thermoanalytical methods with the support of non-thermal analysis such as X-ray powder diffraction and infrared spectroscopy were used for testing structural changes of Moxifloxacin hydrochloride (MOX) stored under four different conditions. Additionally, relative solubilities of the observed crystalline forms were determined by the shake-flask method.

Results: After storage for 1 mo at 0 % relative humidity (RH) and 40 % RH, MOX remained with crystal structure unchanged and shown to have a good physical stability at these conditions. However, when the drug was stocked for 1 mo at 90 % RH and 75 %, a hydrated crystalline form was identified in both conditions. In the solubility assay, it was observed that the hydrated form is less soluble that initial MOX.

Conclusion: Pharmacotechnical wet processes are not be recommended for the pharmaceutical production of this drug because solvent granulation and drying conditions from processing provides a favorable environment for the transition of crystalline forms. According to DSC, TG, PXRD, HPLC and FT-IR results, they showed good correlation with each other and ensure reliable interpretation of solid form stability studies. Moreover, these findings suggest that stability studies of a polymorphism associated with the evaluation of relative solubility are essential for a stable formulation development and to choose between dry or wet granulation processes.



Download data is not yet available.


Food and Drug Administration. Stability Test of New Drug Substance and Products–Guidance for Industry. Draft Guidance; 2005. Available from: URL: [Last accessed on 15 Jul 2015].

Brazil’s National Health Surveillance Agency. Resolution RE n° 398; 2004. Available from: URL: [Last accessed on 15 Jul 2015].

Júlio TA, Zâmara IF, Garcia JS, Trevisan MG. Compatibility of sildenafil citrate and pharmaceutical excipients by thermal analysis and LC–UV. J Therm Anal Calorim 2013;111:2037-44.

Lawecka M, Kosmacinska B, Glice M, Korczak K. The influence of storage conditions on the polymorphic stability of zolpidem tartrate hydrate. J Therm Anal Calorim 2006;83:583-5.

Laszcz M, Trzcinska K, Filip K, Szyprowxka A, Mucha M, Krzeczynski P. Stability studies of capecitabine. J Therm Anal Calorim 2011;105:1015-21.

Kommanaboyina B, Rhodes CT. Trends in stability testing, with emphasis on stability during distribution and storage. Drug Dev Ind Pharm 1999;25:857-68.

Brittain HG. Polymorphism in pharmaceutical solids. 2 nd ed. New York, NY: Informa Healthcare; 1999.

Rustichelli C, Gamberini G, Ferioli V, Gamberini MC, Ficarra R, Tommasini S. Solid-state study of polymorphic drugs: carbamazepine. J Pharm Biomed Anal 2000;23:41-54.

Byrn SR. Solid-State Chemistry of Drugs. 2 nd ed. New York, NY: SSTI-INC; 1999.

Davis TD, Peck GE, Stowell JG, Morris KR, Byrn SR. Modeling and monitoring of polymorphic transformations during the drying phase of wet granulation. Pharmacal Res 2004;21:860-6.

Stowell GW, Behme RJ, Denton SM, Pfeiffer I, Sancilio FD, Whittall LB, et al. Thermally-Prepared polymorphic forms of cilostazol. Am J Pharmacol Sci 2002;91:2481-8.

Lu J. Crystallization and transformation of pharmaceutical solid forms. Afr J Pharm Pharmacol 2012;6:581-91.

Welberry TR, Chan EJ, Goossens DJ, Heerdegen AP. Diffuse scattering as an aid to the understanding of polymorphism in pharmaceuticals. Metall Mater Trans A 2012;43:1434-44.

Brazil’s National Health Surveillance Agency. Resolution RDC n° 31, August 11, 2010. Available from: URL: [Last accessed on 15 Jul 2015].

Chieng N, Rades T, Aaltonen J. An overview of recent studies on the analysis of pharmaceutical polymorphs. J Pharm Biomed Anal 2011;55:618-44.

Endo T, Iwata M, Nagase H, Shiro M, Ueda H. Polymorphism of glimepiride: Crystallographic study, thermal transitions behavior and dissolution study. S T P Pharma Sci 2003;13:281-6.

Wu H, Jone AG. Crystallization, Dehydration, and phase transformations of diastereomeric Salts: L-Ephedrine and D-Tartaric acid. Chem Eng Technol 2012;35:1031-8.

Maximiano FP, Novack KM, Bahia MT, Barreto LLS, Filho MSSC. Polymorphic screen and drug–excipient compatibility studies of the anti chagasic benznidazole. J Therm Anal Calorim 2011;106:819-24.

Jurcek O, Lahtinen M, Wimmer Z, Drasar P, Kolehmainen E. Crystallization, spectral, crystallographical, and thermoanalytical studies of succinobucol polymorphism. J Pharm Sci 2012;101:1794-802.

Grunemberg A, Bosché P. Crystal modification of CDCH a process for its preparation and pharmaceutical formulations comprising this modification. US Patent 1998;5:849,752 A.

Reddy M, Eswaraiah S, Raju VVN, Kumar RR, Srinivasreddy N, Ravindra V. Crystalline form III of anhydrous moxifloxacin hydrochloride and a process for preparation thereof. US patent; 2005. p. 137,227 A1.

Reddy BP, Reddy KR, Reddy RR, Reddy DM, Reddy MM, Reddy DB. Novel polymorph of moxifloxacin hydrochloride. US patent; 2011. p. 212,990 A1.

Turchetta S, Massardo P, Aromatario V. Polymorphs of 1-Cyclopropyl-7-([S,S]-2,8-diazadicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-quinoline carboxylic acid hydrochloride and methods for the preparation ther of. WO patent; 2005. p. 4,240 A1.

Rao DR, Kankan RN, Pathi SL, Puppala R, Gangrade M, Kanathala S. Process for the synthesis of moxifloxacin hydrochloride. US patent; 2010. p. 152,229 A1.

Manne SR, Chakilam N, Srinivasan TR, Achampeta KR. Novel crystalline forms of moxifloxacin hydrochloride and process for preparation thereof. WO patent; 2007. p. 10,555 A2.

Becker A. Novel hydrate form. US patent; 2009. p. 170,893 A1.

Becker A. Novel hydrate form of moxifloxacin monohydrochloride. WO Patent 2007;1:481,137 A1.

European Pharmacopoeia. 6th ed. Germany: Council of Europe; 2008.

Waterman KC, Adami RC. Accelerated aging: prediction of chemical stability of pharmaceuticals. Int J Pharm 2005;293:101-25.

Martins FT, Bonfilio R, Araújo MB, Javier E. Lamivudine salts with improved solubilities. J Pharm Sci 2012;101:2143-54.

Song JS, Sohn YT. Crystal forms of naproxen. Arch Pharm Res 2011;34:87-90.

Bergström CAS, Norinder U, Luthman K, Artursson P. Experimental and computational screening models for prediction of aqueous drug solubility. Pharm Res 2002;19:182-8.

Varanda F, Melo MJP, Caço AI, Dohrn R, Makrydaki FA, Voutsas E, et al. Solubility of antibiotics in different solvents. Part I: Hydrochloride Forms of Tetracycline, Moxifloxacin and Ciprofloxacin. Ind Eng Chem Res 2006;45:6368-74.

Pudipeddi M, Serajuddin ATM. Trends in solubility of polymorphs. J Pharm Sci 2005;94:929-39.



How to Cite

JULIO, T. A., J. S. GARCIA, R. BONFILIO, M. B. D. E. ARAUJO, and M. G. TREVISAN. “SOLID-STATE STABILITY AND SOLUBILITY DETERMINATION OF CRYSTALLINE FORMS OF MOXIFLOXACIN HYDROCHLORIDE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 12, Dec. 2015, pp. 173-7,



Original Article(s)