Hydrophobic drugs crystal surface

If has been observed fhaf by adsorbing surfactants onto the crystal surfaces of poorly water-soluble drugs, dissolution rate can be enhanced. Chen et al. " showed that the dissolution rate of Cl-1041, a poorly water-soluble compound, in 0.1 N HCl may be affected by the surfactant Tween 80. The effects of surfactant are complicated, and many factors are involved. Above the CMC of Tween 80, the adsorption of the surfactant onto the crystal surface may inhibit crystal nucleation on the surface, and causes the dissolution rate to increase. By adsorbing a very small amount of poloxamer onto the hydrophobic drug particle surface. 

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... 

COX-1 and COX-2 have virtually identical tertiary and quaternary structures, but they differ subtly in a long, thin hydrophobic channel extending from the membrane interior to the lumenal surface. The channel includes both catalytic sites and is presumed to be the binding site for the hydrophobic substrate, arachidonate. Both COX-1 and COX-2 have been crystallized in the presence of several different bound NSAID compounds, defining the NSAID-binding site (Fig. 1). The bound drugs block the hydrophobic channel and prevent arachidonate entry The subtle differences between the channels of COX-1 and COX-2 have guided... 

Most drugs and proteins are not soluble in commonly used supercritical fluids, and therefore are processed instead by the SC antisolvent technique,the most popularized being the SEDS, process which is illustrated in Fig. 9. SEDS-produced crystals can have extremely smooth surfaces, as shown by scanning electron microscopy and atomic force microscopy, and the surface may be more hydrophobic and less wettable than crystals grown under more polar conditions.A scanning electron micrograph of acetominophen crystals produced by the SEDS process is shown in Fig. 10. 

Figure 2.9a shows the lipid molecule DMPC. Two layers contacted via the hydrophobic tails lead to spontaneous formation of a double-layer biomimetic membrane that can be transferred to a single-crystal ultraplanar electrochemical Au(lll) surface. The hydrophilic head groups contact the electrode surface via an intermediate water film. Due to the structurally very well-defined assembly, not only AFM and in situ STM but also neutron reflectivity. X-ray diffraction, and infrared reflection absorption spectroscopy (IRRAS) have been employed to support the direct visual in situ STM. Electrochemically controlled structural changes, phase transitions, and the effects of the common membrane component cholesterol (Figure 2.9b) and peptide drugs have been investigated in this way. 

Nanosubstrate, rather than particle, approaches have been utilized in a handful of experiments [33, 34]. HCCA has been crosslinked to SU-8 photoresist polymer via cationic photoiortization, forming a hydrophobic surface. When aqueous sample droplets are applied to this support, surface tension during evaporation essentially concentrates the samples and thus improves the analysis sensitivity [34]. Another engineering approach has been to pre-deposit CHCA matrix crystals by vacuum sublimation onto an ultra-phobic surface. The resultant disposable chips contain an array of matrix spots which concentrate analytes from aqueous matrixes during the drying process. The approach has been applied to the quantitation of drug compounds in biofluids such as serum or urine [31]. 

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