Effects of solute characteristics and concentration on a lyotropic liquid crystal: solute-induced phase change.

We investigated the effects of increased concentrations of the solutes, salicylic acid, benzoic acid, and o-, m-, and p-methoxy benzoic acids, on the anisotropic properties of a liquid crystal solvent. The lamellar liquid crystal was composed of 37% polyoxyethylene (20) isohexadecyl ether in aqueous buffer of pH 1. Phase change, transition temperature, refractive index, and specific resistance of the mesophase were studied in the presence of solutes. Transfer rates of the solutes from the bulk mesophase into aqueous buffer across a lipoidal barrier were used to determine their apparent permeability coefficients. The results indicate that a phase change occurred in the liquid crystal from a lamellar to a hexagonal structure, in the case of salicylic, benzoic, and m-methoxy benzoic acids. However, o- and p-methoxy benzoic acids showed no effect on the packing arrangement of the liquid crystal in the concentration range studied. The occurrence of the phase change was both solute and concentration dependent. Relative values of apparent permeability coefficients of solutes reflected the extent of solute-solvent interactions in the systems.

Comparison of the pharmacokinetics and pharmacodynamics of two commercial products containing glibenclamide.

This investigation was carried out to evaluate the in vitro dissolution as well as the pharmacokinetic and pharmacodynamic properties of two tablet oral dosage forms of glibenclamide, Daonil (product A) and Glucomid (product B). The two products were found to comply with the compendial requirements for both disintegration and content uniformity. Further, the in vitro dissolution characteristics of the two products are similar. The bioavailability and pharmacodynamic studies were carried out on 16 healthy male adult volunteers who received a single dose of each product in a double-blind crossover design. Blood samples were obtained over a 12-h interval and analyzed for serum glucose by glucose-oxidase method, insulin by radioimmunoassay and glibenclamide by a sensitive HPLC assay. The two products were not found to be significantly different with respect to peak serum concentrations (187.9 +/- 13.3 and 167.6 +/- 9.1 ng.ml-1 for A and B, respectively) or to the corresponding peak times (4.2 +/- 0.2 and 4.1 +/- 0.2 h for A and B, respectively). Furthermore, the two products were not found significantly different in the extent of absorption as indicated by the area under serum concentration-time curve (1,118.0 +/- 86.7 and 986.5 +/- 75.1 ng.h.ml-1 for A and B, respectively). The two products were also found to be pharmacodynamically equivalent. This was reflected by the comparable serum glucose and insulin levels. These levels correlated very well with glibenclamide concentrations after the administration of each product. These findings indicate that the two products are bioequivalent in terms of bioavailability and pharmacodynamic effects in normal healthy males.