In-Vivo Analysis and Model-Based Prediction of Tensides' Influence on Drug Absorption.

Depending on their concentrations the surface-active substances, tensides (surfactants) can positively or negatively influence the drug absorption, which is widely used in the design of the dosage forms with controlled release. A problem is that the (in-vivo) rate of absorption cannot be directly measured and for that reason, it is frequently substituted by evaluation of the (in-vitro) dissolution. On other hand, a suitably designed pharmacokinetic model can directly predict virtually all pharmacokinetic quantities including both the rate of absorption and fraction of the dose reaching the blood circulation. The paper presents a new approach to the analysis of the rate of drug absorption and shows its superiority over traditional in-vivo approaches. Both the in-vivo analysis and model-based prediction of the tenside (monolaurin of sucrose) influence on the rate of absorption of the drug (sulfathiazole) after instantaneous per-oral administration to rats are discussed. It was found that 0.001% solution of tenside can increase the rate of absorption by cca 50% and a two-fold increase in absolute bioavailability can be reached. Attention is also devoted to the formal requirements laid on the model's structure and its identifiability. The systematic design, substantiation and validation of a parsimonious predictive model that confirms in-vivo results are presented. The match between in-vivo observations and model-based predictions is demonstrated. The frequently overlooked metaphysics lying behind the compartmental modelling is briefly explained.

Effect of Molecular Composition of Head Group and Temperature on Micellar Properties of Ionic Surfactants with C12 Alkyl Chain.

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.