Nitrofurantoin crystals

Garti, N. Tibika, F. Habit modifications of nitrofurantoin crystallized from formic- acid mixtures. Drug Dev. Ind. Pharm. 1980, 6 (4), 379-398. 

Nitrofurantoin. The urinary tract antibacterial, l-[(5-nitro-2-furanyl)-methyleneamino]-2,4-imidazohdinedione, is prepared by reaction of 5-nitro-2-furancarboxaldehyde with l-anaino-2,4-imidazohdinedione (19,40). Crystallization of the material from nitromethane provides a macrocrystalline form (41) which continues to be employed clinically. 

Three liters of 5% formaldehyde solution (2,625 cc water and 375 cc 40% formalin) containing 50 g of nitrofurantoin is refluxed for about 5 minutes, then filtered hot and cooled. The crystallized product is filtered and washed with 1% formaldehyde solution. It is air dried and then further dried at 65°C. There is obtained 33 g of 3-hydroxymethyl-1 -(5-nitrofur-furylideneamino) hydantoin. 

Marshall, P.V. York, P. Crystallization solvent induced solid-state and particulate modifications of nitrofurantoin. Int. J. Pharm. 1989, 55, 257-263. 

Crystallographically, polymorphs differ from each other in packing arrangement and, at times, in molecular conformation. The antibiotic nitrofurantoin (Fig. 23) exists in two polymorphic forms, denoted a and p (37). In each polymorph the molecule adopts a planar conformation and forms extended sheets which are stacked to make a crystal. However, the hydrogen-bonding interactions... 

EW Pienaar, MR Caira, AP Lotter. Polymorphs of nitrofurantoin. Preparation and X-ray crystal structures of two anhydrous forms of nitrofurantoin. J Crystallogr Spectrosc Res 23 785, 1993. 

The LD,o of nitrofurazone in mice ranges from 374 to 1,400 mg/kg, when the crystals range in size 375 mesh and 60 mesh. Panazone, furazolidone, and di-(hydroxymethyl) panfuran are less toxic when compared with nitrofurazone and nitrofurantoin. 

Yellow crystals from aq formaldehyde. When heated on a melting-point block, loses formaldehyde, then further decomposes at same temp as nitrofurantoin, uv max (2% in dimethylformamide) 367.5, 265 nm (t 17,900, 12,800). therap CAT Antibacterial. 

Nitrofurantoin (A -(5-nitro-2-furfurylidene)-l-aminohydantoin) is widely used as a urinary tract antibacterial agent, but it has poor water solubility, and consequently its dissolution is the ratedetermining step in its bioavailability. Complicating the situation is that the compound can exist in various crystal forms, among which are two anhydrate forms [28]. The structures of the two anhydrates have been reported, and the crystallographic data obtained for these are collected in Table 8. The a-form was crystallized from a hot acetic acid-water solution, while the 3-form was obtained from acetone. 

In some instances, a compound of a given hydration state may crystallize in more than one form, so that the hydrates themselves exhibit polymorphism. One such example is nitrofurantoin, which forms two monohydrates that have distinctly different temperatures and enthalpies of dehydration. The monohydrates have quite different packing arrangements, with Form I possessing a layer structure and Form II exhibiting a herringbone motif The included water molecules play a major role in stabilizing the crystal structures. Whereas water molecules are contained in isolated cavities in Form II, in Form I they are located in continuous channels, and this apparently facilitates the escape of water when these crystals are heated [60]. 

Reduction in particle size, however, is not always desirable. For example, Slow K tablets incorporate a matrix that slowly releases potassium in order to minimize GI tract irritation. Simularly, Macrodantin is a formulation of large crystals of nitrofurantoin, which will dissolve slowly and thereby minimize irritation. 

Mannisto P. The effect of crystal size, gastric content and emptying rate on the absorption of nitrofurantoin in healthy hum an volunteers. IntJ Clin Pharmacol Biopharm (1978) 16,223-8. 

Fig. 3 Crystal structures of nitrofurantoin polymorphs layer stacking (top left) and hydrogen bonding within a layer (lower left) for the a-polymorph and layer stacking (top right) and hydrogen bonding within a layer (lower right) for the P-polymorph. Only the N-H- O hydrogen bonds are indicated. (Adapted from E.W. Pienaar, M.R. Caira and A.P. Lotter, Journal of Ciystallographic and Spectroscopic Research. 23(10), 1993, 785-790. with permission from Kluwer Academic/Plenum Publishers.) View this art in color at WWW. dekker. com.)...

Mode of Action and Pharmacology — This important group of compounds continues to be the subject of theoretical and basic research. During the year a mathematical (molecular orbital) treatment of nltrofuran activity was given It was deduced that bacterial action depends heavily on the reduction of the nltro groups. The effect of crystal size on the rate of peroral absorption of nitrofurantoin and the effect on Its excretion Into the urine and on emesis was studied In rats, dogs and man. Furazolidone as an inhibitor of monoamine oxidase was studied. 

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