Sulfadiazine crystallization

SULPHONAMIDES METHENAMINE Risk of crystalluria Methenamine is only effective at a low pH, and this is achieved by acidifiers in the formulation. Sulfadiazine crystallizes in an acid environment Avoid co-administration... 

Two independent single-crystal structure determinations of silver sulfadiazine have been reported (18,19) which mutually agree in the description of the main features of the structure. Each silver atom is coordinated by three separate sulfadiazine moieties, resulting in a distorted tetrahedral coordination by... 

The X-ray powder diffraction pattern was recorded by means of a Philips diffractometer, type PW 1025/25, using Cu-Ka radiation (X = 1.5418 A). The results are in good agreement with the reported single-crystal data. A strong reflection was observed at 20= 10.2°. All other reflections have an intensity less than 20% relative to this strong (Oil) reflection. The data for the major lines in the diffraction pattern of silver sulfadiazine are given in Table V. 

Sulfadiazine, like other sulfas, has a low urinary solubility, particularly in acid urine. When the urine is alkalinized and pH rises above 7.15, the drug ionizes and forms a soluble salt that is excreted avoiding crystallization. It has been estimated that at a pH of 5.5 about 16 liters of urine will be needed to insure that the sulfadiazine is soluble when excreted following a dose of 4 g per day [5]. Indeed, the urinary solubility of sulfadiazine and its major metabolite, acetylsulfadiazine, are many times higher at a pH of 7.5 than at a pH of 6.5 (sulfadiazine 200 and 28 mg/dl, acetylsulfadiazine 512 and 75 mg/dl, respectively) [30]. The crystals of sulfadiazine and acetylsulfadiazine can be recognized by examining the urine sediment, where they resemble characteristic "sheaves of wheat" [3]. As the crystals transit... 

Prevention of sulfadiazine nephrotoxicity is centered in minimizing crystalluria. This can be accomplished with a high fluid intake (up to 3 liters per day). This may increase solubility of the crystals up to threefold. Nonetheless, continued alkaliniza-tion of the urine with sodium bicarbonate (6 to 12 g/day), assuring that the urine pH is 7.5 or higher, can increase solubility several fold and is very effective. As always, awareness of the possibility of this complication is the best form of prevention. 

Colebunders R, Depraetere K, De Droogh E, Kamper A, Corthout B, Bottiau E. Obstructive nephropathy due to sulfa crystals in two HIV seropositive patients treated with sulfadiazine. Jbr-Btr. 1999 Aug 82(4) 153-4. 

Sodium sulfadiazine and sulfafurazole diolamine in therapeutic doses (1 mg) added to 5% dextrose and 5% dextrose and saline solution have been found to be compatible, yet when added to commercial polyionic solutions (such as Abbott lonosol B, Baxter electrolyte No.2) both rapidly form heavy precipitates. pH and temperature are two vital parameters, but the pH effect is not simply a solubility-related phenomenon. Polyionic solutions of a lower initial pH (4.4-4.6) cause crystallisation of sulfafurazole at room temperature within 2.5 h, the pH values of the admixtures being 5.65 and 5.75 respectively. Other solutions with slightly higher initial pH levels (6.1-6.6) formed crystals only after preliminary cooling to 20°C at pH values from 4.25 to 4.90. If the temperature remains constant, the intensity of precipitation varies with the composition and initial pH of the solution used as a vehicle. 

Greater water solubility can also result from a decrease of the crystal lattice energy, the methyl groups hindering the various intermolecular interactions (hydrogen bonds, dipole-dipole bonds, etc.), hi the antibacterial sulfonamide series, the substitution of the pyrimidine ring of sulfadiazine by one, then two, methyl groups causes an increase in solubility (Table 20.3). A priori, one would expect why the methyl substituted derivatives are less soluble. This for the double reason that they show increased lipophilicity and that they are less dissociated than the parent molecule. 

Urinary tract Bilateral flank pain and progressive oliguria developed over 3 weeks in a 47-year-old woman who took sulfadiazine for toxoplasmosis retinitis [183 ]. Only in a second CT scan (an nnenhanced helical scan with very low attennation for stones) was urolithiasis detected snlfonamide crystals were found in the urine. 

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