Higuchi kinetics

Figure 5. The release of 5-fluorouracil from monolithic dispersions in poly(caprolactone) plotted against the square root of time (Higuchi kinetics). The individual runs are (symbol, % 5-FU in matrix) o, 25% A, 20% , 15% a, 10% , 5%.

Figure 8. Higuchi kinetic plots of the release of 5-fluoro-uracil from EMCF MMA = 50 50 copolymers and monolithic dispersions in poly(caprolactone). The individual runs are (symbol, sample type) o, EMCF MMA powdered material , EMCF MMA pellet form a, FU PC 25 75, pellets. 

Nguyen, T. H., Himmelstein, K. J., and Higuchi, T., Some equilibrium and kinetic aspects of water sorption in poly(ortho esters), Int. J. Pharm.. 25, 1-12, 1985. 

T Higuchi, S Dayal, I Pitman. Effects of solute-solvent complexation reactions on dissolution kinetics Testing of a model by using a concentration jump technique. J Pharm Sci 61 695, 1972. 

In the intramolecular reactions studied by Bruice and Koshland and their co-workers, proximity effects (reduction in kinetic order and elimination of unfavourable ground state conformations) and orientation effects might give rate accelerations of 10 -10 . Hence, these effects can by themselves account for the enhancements seen in most intramolecular reactions. However, a factor of 10 -10 is less than the rate acceleration calculated for many enzyme reactions and certain intramolecular reactions, for example, hydrolysis of benzalde-hyde disalicyl acetal (3 X 10 ) (Anderson and Fife, 1973) and the lactonization reaction of[l] (10 ) where a trimethyl lock has been built into the system. If hydrolysis of tetramethylsuccinanilic acid (Higuchi et al., 1966) represents a steric compression effect (10 rate acceleration), then proximity, orientation, and steric compression... 

Drug release from controlled release matrix tablets has been described by many kinetic theories [20,21]. Fig. 4 illustrates the release profiles of the validated dissolution (experiments 12, 12b and 12c) and the release profiles obtained from fits to the Weibull, Higuchi and Hixson-Crowell models. Figs 5 and 6 show the curves after linear transformation. 

The drug release profile was plotted against time (Figs. 4 and 5) and it was observed that the release kinetics followed both first-order and Higuchi equations up to 75-80% of the cumulative drug release. The micromatrices followed the Higuchi equation (NONLIN package). 

J.B.Schwartz, A.P.Simonelli and W.I.Higuchi, Drug release from wax matrices I. Analysis of data with first-order kinetics and with the diffusion-controlled model, J. Pharm. Sci., 57,274 (1968). 

Germer S, Holland MJ, Higuchi R. High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR. Genome Res Genome Res 2000 10(2) 258-266. 

Release kinetic expression for a tablet (radius rG and thickness /0) can be developed by using Higuchi s pseudo-steady-state approximation and mass balance. With macroscopic observation of the moving boundary of a dispersed drug tablet, Equation (6.76) can be formulated by ... 

In this case, the diffusion of the drug through the core matrix controls the release kinetics. Equation (6.104) is the Higuchi expression. The mathematical expressions for membrane-matrix systems of other geometries can be derived in similar fashion and are shown in Table 6.6. 

Notes ko (%/min), zero-order constant ka (%/min1 2), Higuchi s slope k (%/min"), kinetic constant of Korsmeyer model n, diffusional exponent kA (%/minm), diffusional constant of Peppas and Sahlin model kr (%/min2 ), relaxational constant of Peppas and Sahlin model m, diffusional exponent that depends on geometric shape of releasing device through its aspect ratio (see Table 25). 

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]. 

Figures 42-45 show changes in the different kinetic parameters the Higuchi rate constant, normalized Higuchi rate constant, and relaxation rate constant. To estimate the excipient percolation threshold, these parameters were plotted versus the excipient volumetric fraction plus initial porosity.

Rankell, A. S., and Higuchi, T. (1968), Physics of tablet compression. XV. Thermodynamic and kinetic aspects of adhesion under pressure,/. Pharm. Sci., 58,574-577. 

Bogardus, J. B. and Higuchi, T Kinetics and mechanism of hydnriysis of labile quaternary ammonium derivatives of tettiaty amines. J. Pharm. ScL 71. 729, 1982. 

Kurihara-Beigstrom, T., Flynn, G. L. and Higuchi, W. I. Physicochemical study of percutaneous absorption enhancement by dimethyl sulfoxide Kinetic and thermodynamic determinants of dimethyl sulfoxide mediated mass transfer of alkanols. Journal of Pharmaceutical Sciences 75(5) 479-486, 1986. 

Higuchi WI, Okada T, Stelter GA. Kinetics of rtfiid aggregation in suspensions (comparison of experiments wib be Smoluchowski beory). JPharm Sci 1963 52 49-54. 

Higuchi, W.I. Su, C.C. Park, J.Y. Gulari, E. Mechanism of cholesterol gallstone dissolution. Analysis of the kinetics of cholesterol monohydrate dissolution in taurocholate/ lecithin solutions by the mazer, benedek, and carey models. J. Phys. Chem. 1981, 85 (2), 127-129. 

Higuchi R, Fodder C, Dollinger G, Watson R. Kinetic PCR analysis real-time monitoring of DNA amplification reactions. Biotechnology (NY) 1993 11 1026-30. 

Higuchi and coworkers also demonstrated a genuine first-order kinetics in the condensation reaction of 2-(hydroxymethyl)phenol under basic catalysis. They used LC-MS to monitor the reactant and reaction products. Three main products, dimer 39, trimer 40 and tetramer 41 (Scheme 21), were observed. By measuring the disappearance of the reactant 2-(hydroxymethyl)phenol, the first-order kinetics is confirmed. 

In this chapter, the solubility phenomenon will be developed using fundamental theories. The basic thermodynamics of solubility reveals the relation between solubility, and the nature of the solute and the solvent, which facilitates an estimation of solubility using a limited amount of information. Solubility-related issues, such as the solubility of polymorphs, hydrates, solvates, and amorphous materials, are included in this chapter. In addition, dissolution rate phenomena will also be discussed, as these relate to the kinetics of solubility. A discussion of empirical methods for the measurement of solubility is outside the scope of this chapter, but is reviewed elsewhere (Grant and Higuchi, 1990 Grant and Brittain, 1995). 

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