5-Fluorouracil hydrate

The hydrate formed by photolysis of this substance is one of the few such products (the others are uracil hydrate, 5-fluorouracil hydrate, and uridine hydrate) that have actually been isolated and compared with authentic material of known structure.7 It is nearly the only product formed in the photolysis, is definitely stable at room temperature and neutral pH, and the thermal reversal to dimethyluracil is nearly quantitative. These properties, as Moore observed, make the reaction ideal for mechanistic investigation. Burr and Park have investigated the reaction mechanism by measuring the photolysis rate of dimethyluracil in mixtures of water with several nonaqueous, nonreactive solvents as a function of water concentration.64 The photolysis rate for 10" iM DMU was found to be the same in water-saturated cyclohexane (about 5 x 10-3M in water) as in dry cyclohexane. The photolysis rate in dry, highly purified dioxane was quite insensitive to water, and it was observed that hydrate formation (measured by thin-layer chromatography and by thermal absorbance reversal) became appreciable only at water concentrations above 40%. 

A pharmaceutical cocrystal is composed of an API and complementary molecules including excipients (non-toxic ingredients) or other APIs. Cocrystals may include two or more different components and in most cases to date, two and three component systems are reported with the latter being mostly cocrystalline solvates, e.g., theophylline 5-fluorouracil hydrate. Table 1 presents some examples of pharmaceutical cocrystals and solvates. The term cocrystal generally refers to components that in their pure states are solids at room temperature. It is important to note that a... 

Chloral hydrate Chloramphenicol Cimetidine Ciprofloxacin Clofibrate Danazol Disulfiram Doxycycline Erythromycin Fenofibrate Fluconazole Fluorouracil Fluoxetine Fluvoxamine Gemfibrozil Influenza vaccine Isoniazid Itraconazole Fovastatin Metronidazole Miconazole Moxalactam Neomycin Norfloxacin Ofloxacin Omeprazole Phenylbutazone Piroxicam Propafenone Propoyxphene Quinidine Sertraline Sulfamethoxazole Sulfinpyrazone Tamoxifen Testosterone Vitamin E Zafirlukast... 

Figure 9.17 Release of anticancer drugs from poly(HEMAF-collagen hydrogels. Controlled release of 5-fluorouracil 130), mitomycin C (M, 334), and bleomycin Ml 1,417) into phosphate-buffered water at 37 °C from p(HEMA) polymerized in the presence of drug and 5% eoUagen. The hydrogels were hydrated ( 40% water) throughout the experiment. Adapted from [57].

Condensation of 2-(benzyloxy)ethanol with a mixture of the hydrate and methyl hemiacetal of methyl glyoxalete 638 gave a hemiacetal, which was converted directly with methanesulfonyl chloride to a-chloro ether 639. It condensed with silylated uracil, 5-fluorouracil, and A -acetylcytosine,... 

Theophylline has also been co-crystallized with urea [87] A-(2-ammonioethyl)carba-mate [88], chlorosalicylic acid [89], sulfathiazole, 5-fluorouracil [90], p-nitroaniline [91], succinic acid, malonic acid, maleic acid and oxalic acid [92]. There is evidence that at least one of these co-crystals, between theophylline and oxalic acid, can improve the physical stability of theophylline by protecting it from converting to the less soluble hydrate at high humidities. In this case, oxalic acid and water both hydrogen bond with theophylline at the same site. It is unclear whether or not the occupancy of the hydrogen bonding site by another molecule, in this case oxalic acid prevents the conversion to the hydrate or, if a general decrease in solubility of the oxalic acid co-crystal versus the hydrate is responsible for the protective effects. 

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