Phase solubility profile

The physicochemical properties and dissolution profile of zaleplon -cyclo-dextrin (jSCD) inclusion complex were investigated. The phase solubility profile of Zaleplon with /1CD was classified as AL-type. Stability constant with 1 1 molar ratio was calculated from the phase solubility diagram and... 

Higuchi and Connors (1965) have established a classification of the complexes from the phase solubility profiles (Figure 40.3) obtained from the interaction between the guest and the host when in solution (Higuchi and Connors, 1965). 

FIGURE 40.3 Phase solubility profiles and classification of complexes according to Higuchi and Connors. Sq is the intrinsic solubility of the substrate (the dissolved drug or guest) in the aqueous complexation medium when no ligand (CD) is present. (From Cabral-Marques, H.M., Flavour Frag. J., 25, 313, 2010.)... 

Each L13 individual was evaluated as a potential soluble support in liquid-phase combinatorial synthesis. A great variation in the solubility profiles was observed for the 20 copolymers, the most relevant of which are reported in Table 11.2. The copolymer Mi,2-M2,3 was selected, being very soluble in apolar solvents such as THE and diethyl ether, insoluble in polar solvents such as water and alcohol, and nonswelling in any solvent. It thus resulted complementary to PEG-based supports and... 

As indicated above, an equilibrium condition requires the presence of excess solid phase in equilibrium with the dissolved substance. For a weak acid, it is convenient to consider the various equilibria as dividing a pH-solubility profile... 

Using conventional techniques, it is unlikely that a complete solubility profile can be generated in the prenomination phase due to a lack of compound. However, if the intrinsic solubility of the free base or acid is known, then the solubility can be calculated at any pH. 

The older literature is full of experimental estimations of X, also called the washout coefficient, by the measurement of the gas and rainwater concentration of soluble gases. However, that approach is wrong because a) A is a function of height (it should measured as the vertical gas phase concentration profile and not the surface concentration) and b) a dominant part of the dissolved matter arises from in-cloud scavenging. For sub-cloud scavenging, assuming the washout process to be a first-order process (rfc/rft) = Ac, we can describe the sub-cloud process for gases as well as particles indexes g and p denote the gas and particle, respeetively ... 

Figure 7 shows the dissolution profiles of ketoprofen from ketoprofen powder and physical mixture with methyl-3-CD (molar ratio l l). A High dissolution rate of ketoprofen was observed in the presence of methyl-3-CD. The enhanced dissolution rate may be due to the increase in solubility in the presence of methyl-3-CD as expected from the phase solubility curve. Furthermore, it was found that the... 

The prototypical smart polymer is poly(N-isopropyl acrylamide) (P(NIPAM)), which exhibits an inverse temperature solubility profile in water, that is it is water-soluble below 32 °C but precipitates above 32 °C. The temperature at which this coil-to-globule phase transition occurs is known as the Lower Critical Solution Temperature (LCST), and conveniently this can be modified in P(NIPAM) by incorporation into the polymer chain of more hydrophobic or hydrophilic monomers. Owing to the fact that the LCST is close to body temperature and can readily be modified to just below or just above 37 °C through this co-monomer addition, P(NIPAM) polymers have been widely exploited in biomedical applications. The chemistries and applications of P(NIPAM) have been extensively reviewed elsewhere, [75-81] but even 15 years after one particularly well-cited review, many research groups are working with this remarkably versatile polymer [82-87]. 

Key words Piromidic acid/DM-/8-CD inclusion complex, phase-solubility, DSC, H-NMR, dissolution profile. 

An attempt to reduce the inner oil phase solubility in the external oil phase was achieved by replacing it, for instance, MCT with a mixture of MCT-triacetin (3Ac) or MCT-glycerol monooleate (GMO). In these conditions it was possible to further reduce the release of the drug and the solubility of the inner oil phase into the external oil phase. Figures 7.17 and 7.18 describe the release profiles of flumethrin from multiple emulsions at 25°C where the inner oil phase (Oi) consists of a mixture of MCT and triacetin (3Ac) (Figure 7.17) or glycerol monooleate (GMO) (Figure 7.18) at different ratios. 

FK-506 (37) interferes with IL-2 synthesis and release and has a cyclosporin-like profile, but is considerably more potent in vitro. IC q values are approximately 100-fold lower. This neutral macroHde suppresses the mixed lymphocyte reaction T-ceU proliferation generation of cytotoxic T-ceUs production of T-ceU derived soluble mediators, such as IL-2, IL-3, and y-IFN and IL-2 receptor expression (83). StmcturaHy, FK-506 is similar to sirolimus. Mycophenolate mofetil (33), brequinar (34), and deoxyspergualin are in various phases of clinical evaluation. Identification of therapeutic efficacy and safety are important factors in the deterrnination of their utiUty as immunosuppressive agents. 

Methanol is frequently used to inhibit hydrate formation in natural gas so we have included information on the effects of methanol on liquid phase equilibria. Shariat, Moshfeghian, and Erbar have used a relatively new equation of state and extensive caleulations to produce interesting results on the effeet of methanol. Their starting assumptions are the gas composition in Table 2, the pipeline pressure/temperature profile in Table 3 and methanol concentrations sufficient to produce a 24°F hydrate-formation-temperature depression. Resulting phase concentrations are shown in Tables 4, 5, and 6. Methanol effects on CO2 and hydrocarbon solubility in liquid water are shown in Figures 3 and 4. 

The meaning of the surface excess is illustrated in Fig. 1, in which the solid line represents the actual concentration profile of an adsorbate i, when the bulk concentration of i in the phase a (a = O or W) is c . The hatched area corresponds to be the surface excess of i, T,. This quantity depends on the location of the dividing surface. On the other hand, the experimentally accessible quantity should not depend on the location of the artificially introduced dividing surface. The relative surface excess, which is independent of the location of the dividing surface, is defined by relativizing it with respect to those of certain reference components. In oil water interfaces, the mutual solubility of solvents can be significant. The relative surface excess in Eq. (3) is then related to the surface excesses through... 

Monte Carlo simulation shows [8] that at a given instance the interface is rough on a molecular scale (see Fig. 2) this agrees well with results from molecular-dynamics studies performed with more realistic models [2,3]. When the particle densities are averaged parallel to the interface, i.e., over n and m, and over time, one obtains one-dimensional particle profiles/](/) and/2(l) = 1 — /](/) for the two solvents Si and S2, which are conveniently normalized to unity for a lattice that is completely filled with one species. Figure 3 shows two examples for such profiles. Note that the two solvents are to some extent soluble in each other, so that there is always a finite concentration of solvent 1 in the phase... 

Solubility measurement at a single pH [37-39] under equilibrium conditions is largely a labor-intensive procedure, requiring long equilibration times (12h-7 days). It s a simple procedure. The drug is added to a standard buffer solution (in a flask) until saturation occurs, indicated by undissolved excess dmg. The thermostated saturated solution is shaken as equilibration between the two phases is established. After microfiltration or centrifugation, the concentration of the substance in the supernatant solution is then determined using HPLC, usually with UV detection. If a solubility-pH profile is required, then the measurement needs to be performed in parallel in several different pH buffers. 

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