Caffeine hydrate

Also, hydrates are more soluble in water-miscible solvents than are the corresponding anhydrous forms. For example, the solubility of caffeine hydrate is lower than that of anhydrous caffeine in water but higher in ethanol. The maximum concentration seen may be due to the solubility of the anhydrous crystalline phase or due to a temporary steady state in which the rate of dissolution of the metastable anhydrous form and the rate of crystallization of the stable hydrate are equal. The decreasing concentration represents crystallization of the stable hydrate from a solution supersaturated with respect to it. If the maximum concentration of the solute in the dissolution experiment corresponds to the solubility, then the initial increase in concentration follows the Noyes-Whitney equation [15]. Van t Hoff plots of log solubility versus the reciprocal of temperature give linear relationships (Fig. 16). 

An XRPD system equipped with a heatable sample holder has been described, which permitted highly defined heating up to 250°C [55]. The system was used to study the phase transformation of phenan-threne, and the dehydration of caffeine hydrate. An analysis scheme was developed for the data that permitted one to extract activation parameters for these solid-state reactions from a single non-isothermal study run at a constant heating rate. 

Grant and Higuchi (1990) commented on the solution behavior of solvates in their book on the solubility of organic compounds. The hydrated form will be more stable (less soluble) than the anhydrate in the general case. When the solvate is formed from a nonaqueous solvent that is miscibli in water, the free energy of solution of the solvent into the water reduces the activity of water and increases the apparent solubility of the solvate. An example is cited in which caffeine hydrate is less soluble in water than the anhydrate, but the solubility order reverses in ethanol. 

Caapi, 650, 651 Cabral, 896 Cadaverine, 420 Cadmium, 58 Cafergot, 587 Caffeine, 420 in sport, 98 (metabolite), 1012 Caffeine, anhydrous, 420 Caffeine citrate, 421 Caffeine hydrate, 421 Caffeine monohydrate, 421 Cajuput oil, 470 Cajuputol, 470 Calabar bean, 900 Caladryl, 557 Calan, 1060 Calcamine, 547 Calciferol, 586 Calcipen, 888... 

A typical example of the characterization of a polymorphic system by FT Raman spectroscopy has been given by Gu and Jiang (1995) while an application of the technique with near infrared excitation to the polymorphic cimetidine system has been described by Tudor et al. (1991). The FT Raman technique has been compared to infrared diffuse reflection spectroscopy in the study of the polymorphs of spironolactone (Neville et al. 1992), and the pseudopolymorphic transition of caffeine hydrate (i.e. loss of solvent) has been monitored using the technique (de Matas et al. 1996). 

Suzuki, E. Shirotani, K.-L, Tsuda, Y. and Sekiguchi, K. (1985). Water content and dehydration behavior of crystalline caffeine hydrate. Chem. Pharm. Bull, 33, 5028-35. [115, 125]... 

Trask, A.V. Motherwell, W.D.S. Jones, W. Pharmaceutical cocrystallization engineering a remedy for caffeine hydration. Cryst. Growth Des. 2005, 5, 1013-1021. 

The opposite of deliquescence is efflorescence, which occurs when the crystal loses water of crystallization below a critical water vapour pressure. For example, Griesser and Burger (1995) found that caffeine hydrate lost its water of crystallization even at 61 percent RH. It has also been observed that the three known polymorphs of oxytetracycline have different hygro-scopicity profiles (Burger et al. 1985). 

Migril (Ergotamine tartrate, cyclizine hydrochloride and caffeine hydrate). Wockhardt UK Ltd. Summary of product cha teristics, December 2003. 

Nephrolithiasis/ urolithiasis/ crystalluria IDV Onset Any time after initiation of therapy, especially if 4- fluid intake Symptoms Flank pain and/or abdominal pain, dysuria, frequency pyuria, hematuria, crystallauria rarely, Tserum creatinine and acute renal failure 1. History of nephrolithiasis 2. Fhtients unable to maintain adequate fluid intake 3. High peak IDV concentration 4. tDuration of exposure Drink at least 1.5-2 L of non-caffeinated fluid per day Tfluid intake at first sign of darkened urine monitor urinalysis and serum creatinine every 3-6 months Increased hydration pain control may consider switching to alternative agent stent placement may be required... 

D Southwell, BW Barry. Pentration enhancement in human skin. Effect of 2-pyrroli-done, dimethylformamide and increased hydration on finite dose permeation of aspirin and caffeine. Int J Pharm 22 291-298, 1984. 

Fig. 11) would likely proceed by different mechanisms. Protonation of the diol (IV, Fig. 12) derived from theobromine would lead to ring opening at the C6— Cs position giving an imidazole isocyanate (XVI, Fig. 12). This could readily form XVII which after hydrolysis and loss of C02 would give dimethyl-allantoin (XVIII). On the other hand, the uric acid diol derived from caffeine (X, Fig. 12) cannot fragment by this mechanism. Accordingly, either or both of the processes could Occur via the form of the diol hydrated at the C6 carbonyl group (XIX, Fig. 12) which could readily lose C02 to give XX followed by rearrangement to trimethylallantoin (XXI).

Solids that form specific crystal hydrates sorb small amounts of water to their external surface below a characteristic relative humidity, when initially dried to an anhydrous state. Below this characteristic relative humidity, these materials behave similarly to nonhydrates. Once the characteristic relative humidity is attained, addition of more water to the system will not result in a further increase in relative humidity. Rather, this water will be sorbed so that the anhydrate crystal will be converted to the hydrate. The strength of the water-solid interaction depends on the level of hydrogen bonding possible within the lattice [21,38]. In some hydrates (e.g., caffeine and theophylline) where hydrogen bonding is relatively weak, water molecules can aid in hydrate stabilization primarily due to their space-filling role [21,38]. 

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... 

Byrn SR, Lin C. The effect of crystal packing and defects on desolvation of hydrate crystals of caffeine and L-(-)-l,4-cyclohexadien-l-alanine. J Am Chem Soc 1976 98 4004-4005. 

Hydration and dehydration studies of the solvatomorphs of caffeine (l,3,7-trimethyl-3,7-dihydro-lH-purine-2,6-dione) and theophylline (1,3-dimethyl-3,7-dihydro-lH-purine-2,6-dione) ... 

Many drags can associate with solvents to produce crystalline forms called solvates. When the solvent is water, the crystal is termed a hydrate. Thus more rapid dissolution rates are often achieved with the anhydrous form of a drag. For example, the anhydrous forms of caffeine, theophylline and glutethimide dissolve more rapidly in water than do the hydrous forms of these drags and the anhydrous form of ampicillin is about 25% more soluble in water at 37 °C than the trihydrate. 

Caffeine forms white hexagonal crystals by sublimation. Caffeine has a melting point of 238 Celsius, but the crystals begin to sublime when heated to 178 Celsius. Caffeine is only moderately soluble in water, but more soluble in hot water. The crystals are also moderately soluble in alcohol, acetone, but are much more soluble in methylene chloride, chloroform, and practically insoluble in ether. Caffeine is capable of forming a hydrate, which looses it water of hydration when heated to 80 Celsius. Caffeine is a widely used stimulant, ingested by millions in the form of coffee, tea, ect.,... 

Caffeine occurs as a white powder or as white, glistening needles, usually matted together. It may be compacted or compressed into free-flowing granules or pellets. It is odorless and has a bitter taste. Caffeine is anhydrous or contains one molecule of water of hydration. Its solutions are neutral to litmus. The hydrate is efflorescent in air, and 1 g is soluble in about 50 mL of water, in 75 mL of alcohol, in about 6 mL of chloroform, and in 600 mL of ether. 

During their preparation, drug crystals may incorporate one or more solvent molecules to form solvates. The most common solvate is water. If water molecules are already present in a crystal structure, the tendency of the crystal to attract additional water to initiate the dissolution process is reduced, and solvated (hydrated) crystals tend to dissolve more slowly than anhydrous forms. Significant differences have been reported in the dissolution rate of hydrated and anhydrous forms of ampicillin, caffeine, theophylline, glutethimide, and mercaptopurine. The clinical significance of these differences has not been examined but is likely to be slight. 

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