Drug relaxation rate

To continue the investigation, carbon detected proton T relaxation data were also collected and were used to calculate proton T relaxation times. Similarly, 19F T measurements were also made. The calculated relaxation values are shown above each peak of interest in Fig. 10.25. A substantial difference is evident in the proton T relaxation times across the API peaks in both carbon spectra. Due to spin diffusion, the protons can exchange their signals with each other even when separated by as much as tens of nanometers. Since a potential API-excipient interaction would act on the molecular scale, spin diffusion occurs between the API and excipient molecules, and the protons therefore show a single, uniform relaxation time regardless of whether they are on the API or the excipients. On the other hand, in the case of a physical mixture, the molecules of API and excipients are well separated spatially, and so no bulk spin diffusion can occur. Two unique proton relaxation rates are then expected, one for the API and another for the excipients. This is evident in the carbon spectrum of the physical mixture shown on the bottom of Fig. 10.25. Comparing this reference to the relaxation data for the formulation, it is readily apparent that the formulation exhibits essentially one proton T1 relaxation time across the carbon spectrum. This therefore demonstrates that there is indeed an interaction between the drug substance and the excipients in the formulation. 

Change in relaxation rate, 1/T2 a Method of Quantifying Drug-Membrane Interaction... 

Fig. 3.37 Increase in drug proton relaxation rate (1 /P2) for a series of catamphiphiles as a function of increasing BBPS concentration alone and after addition of increasing concern trations of CaCI2. Note the change in the...

That it is not polymer relaxation but drug dissolution rate, or drug solubility, which accounts for membrane formation can be seen from Figure 15 During the short acetone swelling phase the 0X-loaded core expands, even as a sharply defined drug depleted outside layer is formed complete dissolution occurs only after "v 90 minutes. 

In hydrophilic matrices the drug threshold is less evident than the excipient threshold, which is responsible for the release control [73], In order to estimate the percolation threshold of HPMC K4M, different kinetic parameters were studied Higuchi rate constant, normalized Higuchi rate constant, and relaxation rate constant. The evolution of these release parameters has been studied as a function of the sum of the excipient volumetric percentage plus initial porosity. Recent studies of our research group have found the existence of a sample-spanning cluster of excipient plus pores in the hydrophilic matrix before the matrix is placed in contact with the liquid, clearly influences the release kinetics of the drug [73]. 

Transfer NOE measures the NOESY of a drug in the presence and absence of the target molecule. The cross-relaxation rates are averages due to the conformation of the free and the bound form. Comparison of the NOEs... 

With solvent-activated systems, the active drug is uniformly dispersed within a polymer matrix. The drug is effechvely trapped within the polymer chains. Upon exposure to the biological environment fluids, the matrix swells, causing an increased distance between the polymer chains. This facilitates the release of the drug from the matrix to the smroimding biological environment. The rate of release is dependent upon the relaxation rate of the polymer chains as they are exposed to the fluid media. - ... 

Application of Nuclear Magnetic Resonance to Investigations of Drug-Receptor Interactions - The application of nuclear magnetic resonance spectroscopy to the study of interactions between small molecules and macromolecules has increased appreciably in the past five years. The technique of following the change effected in the relaxation rates of the protons of a small molecule by binding to a macromolecule has now been applied to the study of enzyme-substrate interactions, enzyme-inhibitor interactions, and enzyme-coenzyme inter... 

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