Sulphathiazole solubility

Sulphanilylacetamide, 981 Sulphanilylurea, 995 Sulphaphenazole, 992 Sulphaphenylpyrazol, 992 Sulphapyridine, 992 (metabolite), 994 Sulphapyridine sodium, 993 Sulphapyridine, soluble, 993 Sulphaquinoxaline, 980 Sulphasalazine, 993 Sulphasomidine, 994 Sulphasomizole, xvii Sulphate conjugation, 291 Sulphathiazole, 995 (metabolite), 900, 978 Sulphathiazole sodium, 995 Sulphathiazole, soluble, 995 Sulphatriad, 979, 982, 995 Sulphaurea, 995 Sulphide, 68 Sulphinpyrazone, 996 Sulphinpyrazone sulphide, 996 Sulphinpyrazone sulphone, 996 Sulphonal, xvii Sulphonamides, colour test, 131 gas chromatography, 200... 

Many drugs can exist in more than one crystalline form, for example chloramphenicol palmitate, cortisone acetate, tetracyclines and sulphathiazole, depending on the conditions (temperature, solvent, time) under which crystallization occurs. This property is referred to as polymorphism and each crystalline form is known as a polymorph. At a given temperature and pressure only one of the crystalline forms is stable and the others are known as metastable forms. A metastable polymorph usually exhibits a greater aqueous solubility and dissolution rate, and thus greater absorption, than the stable polymorph. 

Simonelli, A.P. Mehta, S.C. Higichi, W.I. Dissolution rates of high energy sulphathiazole-povidone coprecipitates II characterization of form of drug controlling its dissolution rate via solubility studies. J. Pharm. Sci 1976,65 (3), 355-361. 

Gases or solids may be used as precipitants so long as they meet the requirement of being soluble in the original solvent and do not react with the solute to be precipitated. Ammonia can assist in the production of potassium sulphate by the reaction of calcium sulphate and potassium chloride. In water alone the yield is low, but in aqueous ammonia it is greatly improved. Hydrazine can act in a similar manner (Fernandez-Lozano and Wint, 1979). High pressure CO2 has been used to precipitate sulphathiazole from solution in ethanol the precipitation rate, crystal size and habit can be controlled by varying the CO2 pressure (Kitamura et al., 1997). 

The behaviour of sulphisoxazole in surfactant and glycol solutions has been studied in a series of papers [140,141]. In order to clarify the mechanism of the reduction in rectal absorption of this sulphonamide in the presence of PEG 4000 the effect of this compound on its physicochemical properties was examined. There is a linear relationship between the solubilities of sulphathiazole, sulphapyridine, and sulphisoxazole and the concentration of PEG 4000. The drugs apparently do not form complexes with the glycols it is thought that the reduction in activity is due to a depression of the concentration of the drug in rectal lipid. The effect of non-ionic surfactants is to reduce the absorption of the sulphonamides through solubilization in micelles [141]. Fig. 6.18 indicates the extent of solubilization in polysorbate 80 solutions. Values of apparent distri-... 

Table 6.13 Solubility of sulphacetamide sodium and sulphathiazole sodium in liquid petrolatum and cottonseed oil bases...

Because of the limited solubility of the xanthine derivatives in water, their solubilization by hydrotropes has been the subject of much interest. Such diverse compounds as piperazine [279], sodium salicylate [280], adenosine [281], and diethanolamine [282] have been used to solubilize theophylline. The action of each is presumably due to complex formation. Neish [283] found that caffeine, a xanthine derivative, increased the solubility of a number of aromatic amines, including sulphapyridine, sulphathiazole, and certain dyes. 

It is perhaps relevant to note here that in clinical use sulphonamide mixtures are preferred to single drugs, to minimize the formation of crystal deposition in the kidney. The use of mixtures of related sulphonamides results in enhanced mutual solubility [284]. This is perhaps a case of hydrotropy. Lehr [285] has determined the solubility of a number of sulphonamide combinations, and Frisk et al. [286] have reported on the solubility of the combination sulphadiazine, sulphamerazine, and sulphathiazole. The influence of sulphanilamide on the solubility of sulphathiazole indicated that a 1 1 molecular complex was formed [287]. 

Other techniques involving attempts to utilize the properties of surfactants have included crystallization of poorly soluble drugs such as sulphathiazole, prednisone and chloramphenicol in the presence of small amounts of surfactants [36]. Increases in the rate of solution were observed in each case when polysorbate was used as a 2.5 % solution as the crystallization medium. While the result might be partly ascribed to adsorption of surfactant molecules on to the hydrophobic crystal surface, differential thermal analysis also suggests that some surfactant is incorporated into the crystal structure. Interference of a surfactant in the crystallization process could lead to defect formation. Model studies with... 

Adipic acid has also been used as a model crystal by Fairbrother and Grant [66] in studies of the effect of alkanols and alkanoic acids on habit modification, during crystallization procedures. Crystallization of drugs in aqueous surfactant solutions can lead to enhanced dissolution rates of poorly soluble drugs such as prednisone, sulphathiazole and chloramphenicol [67, 68]. 

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