Kinetics Microspheres

The investigators studied various blends of the three polymers in order to control the rate of chain scission and thus influence the induction period and onset of drug release. None of the blends provided the desired 1-week zero-order kinetics. However, blends of different microsphere types did show promise in vitro (88). 

Recently, Tsakala et al. (90) formulated pyrimethamine systems based on several lactide/glycolide polymers. These studies were conducted with both microspheres (solvent evaporation process) and implants (melt extrusion process). In vitro studies indicated that pyrimethamine-loaded implants exhibited apparent zero-order release kinetics in aqueous buffer whereas the microspheres showed an initial high burst and considerably more rapid drug release. In vivo studies in berghi infected mice confirmed that the microspheres did not have adequate duration of release for practical application. However, the implants offer promise for future clinical work as more than 3 months protection was observed in animals. 

Extensive studies have been reported with cisplatin in the field of chemoembolization (59,98). Microspheres prepared by a solvent evaporation procedure were characterized in vitro and critical processing parameters in regard to drug release kinetics were identified. 

Juliano, R. L. (1988). Factors effecting the clearance kinetics and tissue distribution of liposomes, microspheres and emulsions,... 

Grattard, N., Pernin, M., Marty, B., Roudaut, G., Champion, D. and Le Meste, M. (2002) Study ofrelease kinetics of small and high molecular weight substances dispersed into spray-dried ethylcellulose microspheres. Journal of Controlled Release, 84, 125-135. 

Wu et al. (2000) showed the formation of self-assembled nanoparticles of P(SA -block-EG) in an aqueous environment and studied their degradation as a function of pH and temperature. Fu et al. (2002) repeated the synthesis of P(SA-Wock-EG) and studied the morphology and erosion kinetics of microspheres which they propose as vehicles for mucosal drug delivery. 

Glass microspheres offer only a limited volumetric hydrogen storage density of less than 20 kg m [9]. Furthermore, a glass sphere with the pressurized system is not in equilibrium and only kinetically hindered in diffusion. 

The microspheres were also evaluated for their release kinetic profiles and stability at three temperatures. 

Four methods have been developed for enzyme immobilization (1) physical adsorption onto an inert, insoluble, solid support such as a polymer (2) chemical covalent attachment to an insoluble polymeric support (3) encapsulation within a membranous microsphere such as a liposome and (4) entrapment within a gel matrix. The choice of immobilization method is dependent on several factors, including the enzyme used, the process to be carried out, and the reaction conditions. In this experiment, an enzyme, horseradish peroxidase (donor H202 oxidoreductase EC 1.11.1.7), will be imprisoned within a polyacrylamide gel matrix. This method of entrapment has been chosen because it is rapid, inexpensive, and allows kinetic characterization of the immobilized enzyme. Immobilized peroxidase catalyzes a reaction that has commercial potential and interest, the reductive cleavage of hydrogen peroxide, H202, by an electron donor, AH2 ... 

Short heat treatments were found to result in a loss of blowing gas. It is probable that in this case gas evolution precedes polymerization and the formation of a film to keep the gas within the particle. By contrast, for longer treatment times polymerization precedes gas evolution and microspheres are formed. Data on the reaction kinetics during microspheres formation are given in36). 

Polyphosphazenes are a relatively new class of biodegradable polymers. Their hydrolytic stability or instability is determined not by changes in the backbone structure but by changes in the side groups attached to an unconventional macromolecular backbone. Synthetic flexibility and versatile adaptability of polyphosphazenes make them unique for drug delivery applications. For example, Veronese et al.18 prepared polyphos-phazene microspheres with phenylalanine ethyl ester as a phosphorous substituent and loaded it with succinylsulphathiazole or naproxen. The kinetics of release from these matrices were very convenient in yielding local concentrations of the two drugs that are useful per se or when mixed with hydroxyapatite for better bone formation. Polyphosphazene matrices are also considered as potential vehicles for the delivery of proteins and vaccines.19... 

Figure 7.36a-c shows the forward and reverse components of the square wave current. When the chemical kinetics is fast enough to achieve kinetic steady-state conditions (xsw > 1.5 and i + k2 > (D/rf), see [58,59]), the forward and reverse responses at discs are sigmoidal in shape and are separated by 2 sw. This behavior is independent of the electrode geometry and can also be found for spheres and even for planar electrodes. It is likewise observed for a reversible single charge transfer at microdiscs and microspheres, or for the catalytic mechanism when rci -C JDf(k + k2) (microgeometrical steady state) [59, 60]. 

While several explanations for the particle concentration effect have been presented, VanHoof and Andren (1990) suggested a kinetic explanation rather than a thermodynamic one. Equilibrium sorption is independent of particle size, but kinetics is not, with small particles reaching equilibrium faster. A solids concentration effect on 4-chlorobi-phenyl was observed in an aqueous suspension of polystyrene microspheres. The apparent inverse relationship of 4-chlorobiphenyl partitioning with particle concentration diminished with time, demonstrating that nonattainment of equilibrium results in the observed phenomenon. 

The catalytic, synthetic, hormonal, and inhibitory activities that have been found in proteinoids or proteinoid microspheres are listed in Table 2. The possibility that metabolic activities found were due to contamination by micro-organisms is denied by experiments under aseptic condition or by the several experimental observations. The activities of proteinoids are generally weak. In some cases, proteinoids act several orders of magnitude more slowly than do modern enzymes or organisms, but free amino acids or Leuchs polypeptides usually have no activity or less than the proteinoid composed of the same amino acids. In general, activities of proteinoids increase approximately in proportion to its molecular weight. One or more of the proteinoids has been found to meet the salient requirements of enzymes such as Michaelis-Menten kinetics, pH-activity curves, etc. 

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