PHARMACEUTICAL COCRYSTAL OF PRULIFLOXACIN WITH NICOTINAMIDE
Keywords:Cocrystallization, Prulifloxacin, Nicotinamide, Solvent evaporation method
Objective: Cocrystals have been increasingly recognized as an attractive alternative for solid forms of drug products. In this work nicotinamide (NCT) was employed to form the cocrystal with the active pharmaceutical ingredient prulifloxacin (PF).
Methods: The PF-NCT cocrystal was prepared by employing slow evaporation and solution crystallization methodology from acetone as a solvent. The PF-NCT cocrystal was characterized by powder X-ray diffraction (PXRD), infrared (IR) spectroscopy, raman spectroscopy, IH NMR spectroscopy and differential scanning calorimetry (DSC). The PF-NCT cocrystal was then subsequently evaluated for pharmaceutical relevant properties such as aqueous solubility and hygroscopicity.
Results: Synthesis of cocrystal of prulifloxacin with nicotinamide were successfully carried out by solvent evaporation and solution crystallization methods using acetone solvent. The results from Powder X-ray diffraction, DSC, IR, Raman spectroscopic analysis revealed the formation of cocrystal of prulifloxacin and nicotinamide.
Conclusion: The PF-NCT cocrystal is moderately hygroscopic and exhibit enhanced solubility than the pure drug. This study confirms cocrystallization offers a valuable way to improve the physicochemical properties of the API.
Kerns EH. High throughput physicochemical profiling for drug discovery. J Pharm Sci 2001;90:1383-858.
Hauss DJ. Oral lipid based formulations. Adv Drug Deliv Rev 2007;59:667-76.
Leunner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000;50:47-60.
Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavilability of poor water soluble drugs. Drug Discovery Today 2007;12:1068-75.
Rodiguez-Spong B, Price CP, Jayasankar A, Matzger AJ, Rodriguez-Hornedo N. General principles of pharmaceutical solid polymorphism: a super molecular respective. Adv Drug Deliv Rev 2004;56:241-74.
Blagden N, Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev 2007;59:617-30.
Shan N, Zaworotko MJ. Polymorphic crystal forms and cocrystals in drug delivery. Drug Discovery Today 2007;13:440-6.
Shultheiss N, Newmann A. Pharmaceutical cocrystals and their physicochemical properties. Cryst Growth Des 2009;9:2950-67.
Ter Horst JH, Deij MA, Cains PW. Discovering new cocrystals. Cryst Growth Des 2009;9:1531-7.
Seefeldt K, Miller J, Alvrez-Nunez F, Rodriguez-Hornedo N. Crystallization pathways and kinetics of carbamazepine-nicotinamide cocrystals from the amorphous state by in situ thermomicroscopy, spectroscopy, and calorimetry studies. J Pharm Sci 2007;96:1147.
Kim S, Li Z, Tseng YC, Nar H, Spinelli E, Varsolona R, Reeves JT, et al. Development and characterization of a cocrystal as a viable solid form for an active pharmaceutical ingredient. Org Process Res Dev 2013;17:540-8.
Chadwick K, Davey R, Cross W. How does grinding produce cocrystals? Insights from the case of benzophenone and diphenylamine. Cryst Eng Commun 2007;9:732-4.
Hickey MB, Peterson ML, Scoppettuolo LA, Morristte SL, Vetter A, Guzman H, et al. Performance comparison of a cocrystal of carbamazepine with marketed product. Eur J Pharm Biopharm 2007;67:112-9.
Shattock TR, Arora KK, Vishweshwar P, Zaworotko MJ. Hierachy of supermolecular synthons: persistent carboxylicacid pyridine hydrogen bonds in cocrystals that also contain a hydroxyl moiety. Cryst Growth Des 2008;8:4533-45.
Palmer DS, Llinas A, Morao I, Day GM, Goodman JM, Glen RC, et al. Predicting instrinsic aqueous solubility by a thermodynamic cycle. Mol Pharm 2008;5:266-79.
Zhang GGZ, Henry RF, Borchardt TB, Lou XC. Efficient cocrystal screening using solution-mediated phase transformation. J Pharm Sci 2007;96:990-5.
Takata N, Shiraki K, Takano R, Hayashi Y, Tarada K. cocrystal screening of stanolone and metastanolone using slurry crystallization. Cryst Growth Des 2008;8:3032-7.
Shan N, Toda F, Jones W. Mechano chemistry and cocrystal formation: effect of solvent on reaction kinetics. Chem Commun 2002;2372-3.
Friscic T, Trask AV, Motherwell WDS, Jones W. Guest directed assembly of caffine and Succinicacid into topologically different heteromolecular host networks upon grinding. Cryst Growth Des 2008;8:1605-9.
Friscic T, Trask AV, Motherwell WDS, Angew. Screening for inclusion compounds and systematic construction of three component solids by liquid-assisted grinding. Chem Int Ed 2006;45:7546-50.
Araake M, Hara T, Watabe H, Nishino T. In vitro antibacterial activity of prulifloxacin a new oral fluoroquinolone. Jpn J Antibiot 2002;55:778-90.
Corey EJ, Czako B, Kurthi L. Molecules and medicine. Wiley; 2007. p. 135.
Akai J, Nishida H. Crystals of quinoline carboxylic acid solvate 2006;EP1626051.
Pathi SL, Rao DR, Kakan R, Chinimilli V. Crystalline form of prulifloxacin and process for its preparation 2012;WO2012/001357A1.
Nanjwade VK, Manvi FV, Ali SM, Nanwade KB. Characrization of Prulifloxacin-salicylic acid complex by IR, DSC and PXRD. JPBMS 2011;5:01-6.
Knip M, Douek IF, Moore WPT, Gillmor HA, Mclean AEM, Bingley PJ, et al. Safety of high-dose nicotinamide. Diabetologia 2000;43:1337-45.
Good DJ, Rodriguez-Hornedo N. Solubility advantage of pharmaceutical cocrystals. Cryst Growth Des 2009;9:2252-64.