Formulation and hypoglycemic activity of pioglitazone-cyclodextrin inclusion complexes.

Pioglitazone is a thiazolidinedione derivative used for the treatment of type 2 diabetes. The drug's poor aqueous solubility and slow dissolution rate are the main causes of its limited therapeutic action in some cases. The aim of the present study is to formulate a more soluble product of pioglitazone at physiological pH. The potential interaction of pioglitazone with cyclodextrins and water-soluble polymers was investigated to enhance the drug's bioavailability and improve its efficacy. The interaction of pioglitazone with ß-cyclodextrin, HP-ß-cyclodextrin, and dimethyl-ß- cyclodextrin was evaluated by spectrophotometric and solubility methods. Both methods revealed the formation of 1:1 inclusion complexes. The phase solubility diagram of pioglitazone-cyclodextrin systems with or without water-soluble polymers was classified as the AL type. The solubilization strength of cyclodextrins and the apparent stability constant of systems increased upon addition of water-soluble polymers. Inclusion complexes of pioglitazone in cyclodextrins with or without watersoluble polymers were prepared by the kneading method. Binary systems were characterized and confirmed by IR spectroscopy, X-ray diffractometry, and thermogravimetric analysis. The dissolution rates of pioglitazone, pioglitazone-cyclodextrin physical mixtures, pioglitazone-cyclodextrin complexes, and ternary systems containing watersoluble polymers were determined using a USP dissolution tester; results revealed enhanced dissolution properties of cyclodextrin complexes compared to drug and physical mixtures, and all of the ternary systems displayed higher dissolution efficiency than corresponding binary systems. The permeation of pioglitazone and pioglitazonecyclodextrin complexes through a cellulose membrane with and without water-soluble polymers (PVP and HPMC) present increased and the release pattern follows the kinetics of a Higuchi equation. Assessment of the hypoglycemic effect of the free drug and its cyclodextrin complexes in normal rats via measurement of blood glucose levels (BGL) after administration of a single oral dose revealed that the hypoglycemic effect of pioglitazone-cyclodextrin complexes was greater than that of the free drug and that a pioglitazone-DM ß-cyclodextrin complex had the greatest effect. In conclusion, the physicochemical and biological properties of pioglitazone improved as a result of complexation with cyclodextrins, and the improvement of physicochemical properties was more prominent after water-soluble polymers were associated with pioglitazone-cyclodextrin systems.

Correlation between the spermicidal activity and the haemolytic index of certain plant saponins.

The haemolytic index, the spermicidal efficacy and the effect on the vaginal mucosa of some plant saponins were determined. It was proved that a certain correlation exists between the haemolytic index and the spermicidal efficacy of these saponins. Saponin of Gypsophila paniculata was proved to be relatively superior when used in aqueous solution or when formulated in polyethylene glycol ointment base.

PIP: The attempt was made to evaluate some plant saponins for their spermicidal efficiency and to correlate this efficacy with the hemolytic index of each saponin. Testing was also done for irritant behavior of these saponins and the formulation of the most effective and least irritant 1 for semisolid application. Of the tested saponins, Gypsophila paniculata saponin was found to be the most effective on human sperms. This efficient spermicidal activity was associated with a high hemolytic index and low irritant behavior. The data obtained showed a correlation between the values of the hemolytic indices and the spermicidal activity of all the plant saponins except that of Terminalia horrida.

Physical parameters of chlorphenamine maleate suppositories and its release as a function of particle size, concentration and nature of the base.

Suppositories of chlorphenamine maleate were formulated. The influence of particle size and percentage concentration of chlorphenamine maleate on the physical standards of its suppositories as well as the release of the drug from oily base (cacao butter), water-soluble base (carbowax) and emulsifying base (Witepsol) has been investigated.