The paper presents a system-based approach for predicting the changes of the plasma concentration and the therapeutic effect of sodium p-aminosalicylate caused by addition of surfactant Tween 80 to a liquid dosage form. A predictive pharmacokinetic model of the oral administration is synthetized together with the corresponding model of its parametric sensitivity. The sensitivities predicted by the model are then compared to those obtained from the in-vi vo experiment. The close correspondence between them is used to prove the model correctness. Similarly the Emax model of the therapeutic effect predicts influences of the added surfactants on the therapeutic effect. In this context, the problem of determining an optimal absorption rate for the desired time course of the therapeutic effect is solved. As a by-product this study, it is shown that the (in-silico generated) sensitivity of plasma concentration to the drug absorption rate may provide information on how far the in-silico experiment can serve as a substitute for in-vivo bioavailability and bioequivalence studies
The paper analyses influences of the temperature and hydrophilic groups on micellar properties of ionic surfactants with 12-carbonic hydrophobic chains. The aim is to assess the impact of hydrophilic groups and temperature on thermodynamic parameters and micellization. This knowledge is indispensable for the formulation of new dosage forms. The method uses conductometric measurements. The following hydrophilic groups are analyzed: trimethylammonium bromide, trimethylammonium chloride, ethyldimethylammonium bromide, didodecyldimethylammonium bromide, pyridinium chloride, benzyldimethyl-ammonium chloride, methylephedrinium bromide, cis and trans-[(2-benzyloxy)-cyclohexyl-methyl]-N, N-dimethylammonium bromide, sodium sulphate and lithium sulphate. Except for a few cases, there is a good agreement between values of critical micellar concentrations (CMC) and critical vesicle concentration (CVC) obtained here and those which were obtained by other authors and/or by other physicochemical methods. Values of the CMC are compared with respect to the molar masses of hydrophilic groups. It was found that CMC values increased non-linearly with increasing system temperature. The degrees of counterion binding and thermodynamic parameters, like the standard molar Gibbs energy, enthalpy and entropy of micellization are determined and discussed in detail. The results obtained will be incorporated into in silico processes of modeling and design of optimal dosage forms, a current interdisciplinary research focus of the team.
In this paper the synchronous generator excitation control is designed using the model reference control approach and its predictive extension. The control objective is to satisfy requirements on the synchronous generator performances imposed by the transmission system operator. The structure of both controllers is expressed in the form of modified Laguerre network. The efficiency of the proposed control design procedure is illustrated by simulation of the 259 MVA synchronous generator of the nuclear power plant Mochovce in Slovakia.K e y w o r d s: model reference control, predictive control, Laguerre model, synchronous generator
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