Hydrates theophylline monohydrate

X-ray powder diffractometry can be used to study solid state reactions, provided the powder pattern of the reactant is different from that of the reaction product. The anhydrous and hydrated states of many pharmaceutical compounds exhibit pronounced differences in their powder x-ray diffraction patterns. Such differences were demonstrated earlier in the case of fluprednisolone and carbamazepine. Based on such differences, the dehydration kinetics of theophylline monohydrate (CvHgN H20) and ampicillin trihydrate (Ci6H19N304S 3H2O) were studied [66]. On heating, theophylline monohydrate dehydrated to a crystalline anhydrous phase, while the ampicillin trihydrate formed an amorphous anhydrate. In case of theophylline, simultaneous quantification of both the monohydrate and the anhydrate was possible. It was concluded that the initial rate of this reaction was zero order. By carrying out the reaction at several... 

Theophylline, 1011 in sport, 98 (metabolite), 421 quantification in plasma, 26 therapeutic drug monitoring, 110 Theophylline, anhydrous, 1011 Theophylline cholinate, 1011 Theophylline ethylenediamine compound, 1011 Theophylline hydrate, 1011 Theophylline monoethanolamine, 1011 Theophylline monohydrate, 1011 Theophylline olamine, 1011 Theophylline sodium aminoacetate, 1011 Theophylline sodium glycinate, 1011 Theophylline-7-acetic acid, 310 Theophylline-aminoisobutanol, 408 Theospan, 1011 Theovent, 1011 Thephorin, 880 Theralax, 397 Theralene, 1046 Therapav, 848... 

The same co-crystal hydrate is also obtained by the neat grinding of theophylline hydrate with anhydrous dtric add, the neat grinding of anhydrous theophylline with dtric acid monohydrate, as well as the neat grinding of theophylline monohydrate with dtric add monohydrate. Neat grinding of anhydrous theophylline and anhydrous dtric acid, by contrast, leads to the formation of an anhydrous co-crystal of 1 1 stoichiometry (Figure 8.18(c)). The similarity of the supramolecular motifs within the co-crystal hydrate to those observed in theophylline monohydrate and citric acid monohydrate crystals (Figure 8.19) suggests that, in the presence of water, the co-crystal hydrate could... 

Figure 8.19 Similar structural motifs between (a) a co-crystal hydrate of theophylline and citric acid, (b) citric acid monohydrate and (c) theophylline monohydrate. ...

Case study theophylline anhydrate and monohydrate The type of structural information that can be obtained from the study of the x-ray diffraction of single crystals will be illustrated through an exposition of studies conducted on the anhydrate and hydrate phases of theophylline (3,7-dihydro-l,3-dimethyl-LH-purine-2,6-dione). The unit cell parameters defining the two phases are fisted in Table 7.2, while the structure of this compound and a suitable atomic numbering system is located in Fig. 7.3. 

Savolainen et al. investigated the role of Raman spectroscopy for monitoring amorphous content and compared the performance with that of NIR spectroscopy [41], Partial least squares (PLS) models in combination with several data pre-processing methods were employed. The prediction error for an independent test set was in the range of 2-3% for both NIR and Raman spectroscopy for amorphous and crystalline a-lactose monohydrate. The authors concluded that both techniques are useful for quantifying amorphous content however, the performance depends on process unit operation. Rantanen et al. performed a similar study of anhydrate/hydrate powder mixtures of nitrofurantoin, theophyllin, caffeine and carbamazepine [42], They found that both NIR and Raman performed well and that multivariate evaluation not always improves the evaluation in the case of Raman data. Santesson et al. demonstrated in situ Raman monitoring of crystallisation in acoustically levitated nanolitre drops [43]. Indomethazine and benzamide were used as model... 

Figure 8 shows the solubility of the anhydrous and monohydrate forms of theophylline as a function of temperature (34). Just as the free energy difference between polymorphs can be calculated from the solubility difference, the free energy of hydration can be obtained from the solubility difference. 

The transition of sulfaguanidine from a monohydrate form to an anhydrous form in the presence of differing water vapor pressures586 conformed to different rate equations among those listed in Table 10. Similarly, the dehydration kinetics of hydrated theophylline614 of different particle sizes was also described by different rate equations. Polymorphic transitions of anhydrous theophylline in tablets conformed to different rate equations depending on the tablet size and pore size.583-584... 

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