Drug hydrate analysis

In an oligonucleotide-drug hydrate complex, the appearance of a clathrate hydrate-like water structure prompt a molecular dynamics simulation (40). Again the results were only partially successful, prompting the statement, "The predictive value of simulation for use in analysis and interpretation of crystal hydrates remains to be established." However, recent molecular dynamics calculations have been more successful in simulating the water structure in Ae host lattice of a-cyclodextrin and P-cyclodextrin in the crystal structures of these hydrates (41.42). 

A number of refinements and applications are in the literature. Corrections may be made for discreteness of charge [36] or the excluded volume of the hydrated ions [19, 37]. The effects of surface roughness on the electrical double layer have been treated by several groups [38-41] by means of perturbative expansions and numerical analysis. Several geometries have been treated, including two eccentric spheres such as found in encapsulated proteins or drugs [42], and biconcave disks with elastic membranes to model red blood cells [43]. The double-layer repulsion between two spheres has been a topic of much attention due to its importance in colloidal stability. A new numeri-... 

Our next step was to assess whether the methodology used to calculate hydration free energy differences for simple carbonyl-containing compounds9 was suitable for heteroaromatic bases. Since our drug design strategy entailed analysis of purine riboside hydration, a series of azanaphthalenes was initially selected for analysis in part because of their structural similarity to purines and in part because of the extensive... 

In the case of most chemicals, urine analysis provides less precise information than blood serum analysis about the donor s instantaneous state of health. This is because the chemicals build up over time as filtered by the kidney and are diluted by variable amounts of water in the bladder depending upon the donor s hydration state. However, the easy availability of urine, compared with blood, means that repeated urinalysis can monitor a person s state of health with little pain or disruption. As noted above, another major use of urine analysis is the detection of breakdown products from medications or illegal drugs. 

Wardman P, Dennis MF, Everett SA, Patel KB, Stratford MRL, Tracy M (2003) Radicals from one-electron reduction of nitro compounds, aromatic N-oxides and quinones the kinetic basis for hypoxia-selective, bioreductive drugs. Biochem Soc Symp 61 171-194 Warman JM, de Haas MP, Hummel A, van Lith D, VerberneJB, Loman H (1980) A pulse radiolysis conductivity study of frozen aqueous solutions of DNA. Int J Radiat Biol 38 459-459 Warman JM, de Haas MP, Rupprecht A (1996) DNA a molecular wire Chem Phys Lett 249 319-322 Warters RL, Lyons BW (1992) Variation in radiation-induced formation of DNA double-strand breaks as a function of chromatin structure. Radiat Res 130 309-318 Warters RL, Hofer KG, Harris CR, Smith JM (1977) Radionuclide toxicity in cultured mammalian cells Elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 12 389-407 Weiland B, Huttermann J (1998) Free radicals from X-irradiated, dry and hydrated lyophilized DNA as studies by electron spin resonance spectroscopy analysis of spectral components between 77 K and room temperature. Int J Radiat Biol 74 341-358 Weinfeld M, Soderlind K-JM (1991) 32P-Postlabeling detection of radiation-induced DNA-damage identification and estimation of thymine glycols and phosphoglycolate termini. Biochemistry 30 1091-1097... 

The analysis of the release profiles and the kinetic data indicate two different behaviors and a sudden change between them. In the first behavior, which corresponds to the matrices that release the drug at slow rates, the release was controlled by the fully hydrated gel layer. For these matrices, erosion of the hydrophilic gel structure has shown an important influence on drug release. This is indicated by the better fit of the drug release kinetics to the zero-order equation, the n value of... 

Therefore, the results obtained from the kinetics analysis are in agreement with the release profiles, indicating a clear change in the release rate and mechanism between matrices containing 90 and 95% w/w of drug (5-10% w/w of excipient). The existence of a critical point can be attributed to the excipient percolation threshold. From the point of view of percolation theory, this means that above 10% w/w of FIPMC K4M, the existence of a network of HPMC (able to form a hydrated layer from the first moment) controls the drug release. 

Often the solvates (hydrates) are not detected since, according the corresponding phase diagram, at ambient temperature, they can be partly or completely dissociated. Suspensions of hydrates in water should shift the equilibrium toward the formation of the stable hydrated form. The ability of DSC measurements at subambient temperatures allow to determine phase transitions. Giron et al. proposed to use the melting peak of freezable water for the analysis of suspensions of drug substances in water in combination with TG for the determination of the number of molecules of water bounded as hydrates. 

In a retrospective analysis of spontaneous adverse event reports encompassing more than 430, 000 patients who had received zoledronic acid between August 2001 and March 2003, only 72 cases of renal failure were identified by the US Food and Drug Administrahon [78, 79]. It should be noted, however, that patients with risk factors for renal deterioration, including advanced cancer, previous bisphosphonate exposure, and use of nonsteroidal anti-inflammatory medications, may have contributed to the progression of renal failure [79]. Because of the potentially serious nature of this adverse event, it is recommended to monitor renal funchon in patients with cancer before each infusion of zoledronic acid, provide adequate hydration, and modify or discontinue treatment if renal complications occur [30, 78, 79]. 

Another simple identification determination of a drug substance is the melting point. A more sophisticated technique is differential scanning calorimetry (Fig. 1). The melting characteristic may be used for identification and is especially suitable for a polymorphic system. The existence of one or more polymorph forms can be identified. For the identification of hydrates or solvates, thermal gravimetric analysis (TGA) is used (Fig. 2). 

DSC analysis is often used in conjunction with structural techniques during the characterization of hydrate and solvate systems, with the thermal method being used to pinpoint the transition temperature range over which the bound water or solvent can be liberated. For instance, although a number of solvate forms could be crystallized for ethynylestradiol, the different solvent molecules were found incapable of exerting any effect on the conformation of the drug [104]. DSC... 

Several hundreds of linear relationships between various kinds of (mostly nonspecific) biological data and n-octanol/water partition coefficients have been published e.g. [18, 182]). However, the choice of n-octanol/water as the standard system for drug partitioning must be reconsidered in the light of some recent results. Principal component analysis of partition coefficients from different solvent systems [188 —190] shows that lipophilicity depends on solute bulk, polar, and hydrogen-bonding effects [189] isotropic surface areas, i.e. areas where no water molecules bind and hydrated surface areas, were correlated with the first and the second principal components of such an analysis [190]. 

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