Interaction of trimeprazine with cyclodextrins in aqueous solution.

The synergistic effect of pH and complexation with cyclodextrins on some properties of phenothiazine derivative--trimeprazine (TM) was investigated. Inclusion complexes of TM with beta-cyclodextrin (beta-CD) and its substituted derivatives (DM-beta-CD, HP-beta-CD, beta-CDsulf) were obtained in phosphate buffer solution of different pH (6.8; 5.9; 5.0) using spectral and phase solubility methods Irrespective of the method of determination the apparent stability constant of TM-beta-CD system was the greatest and, in the case of the spectral method, its value increased with decreasing pH. The results obtained by the method of solubility diagrams indicate that increase in solubility of the basic form of TM, following decrease of pH, resulted rather from its transformation to a better soluble, protonated form than its inclusion into CD cavity. The thermodynamic parameters estimated from linear Van't Hoff plot suggest that the van der Waals forces were operating in the TM-beta-CD system. The effect of pH and the presence of cyclodextrins on photostability of TM was also investigated. The photochemical decomposition of TM in the absence and in the presence of CD proceeds according to the first order reaction. The charged form of TM was more stable than free base of this drug and hence the stability of TM increases first of all as result of a decrease in pH and then owing to the presence of CD. The data of 13C NMR analysis indicate that the aromatic portion of TM molecule tends to the interior of CD.

Effect of cyclodextrin complexation on aqueous solubility and photostability of phenothiazine.

The effect of cyclodextrin (beta-CD, gamma-CD and substituted beta-CD derivatives) complexation on the solubility and photostability of phenothiazine (Ph) was compared. The phase solubility method was applied to calculate the stability constants of soluble 1:1 or 1:2 inclusion compounds formed between Ph and CDs. Photochemical decomposition in solution of phenothiazine alone and in the presence of beta-CD or beta-CD derivatives, was found to proceed according to the two stage first-order reaction and in the case of gamma-CD, in a single stage reaction. Formation of solid inclusion complexes of Ph with CDs was evaluated using IR, 13C NMR and DSC studies. The influence of the complexation technique in the solid state (kneading, heating and freeze-drying) on the solubility of Ph was compared. It was establish that the improvement in solubility and stability of Ph was dependent on the kind of CD. When the complexation proceeded in solution it was more effective.

[Evaluation of the liberation of aluminum and magnesium ions from preparations made up of antacid ]. / Badanie uwalniania jonów glinu i magnezu z preparatów zlozonych z grupy antacida.

Releasing of Al3+, Mg2+ and Ca2+ cations from 24 antacid mixtures, 15 from which were prepared in our Department and 9 of foreign origin, during the neutralization reaction of HC10,1 mol/dm3 was determined. Duration of action at pH 3-5 and acid consuming capacity of HCl 1 mol/dm3 acc. to USP XX was also performed. It was stated that magnesium cations were first than Al3+ released from the antacid mixtures during the neutralization reaction.

[Drug interactions during storage of mixtures of the antacid group. II. Effect of temperature on the formation of hydrotalcite in neutralizing suspensions]. / Badanie oddzialywan zachodzacych podczas przechowywania mieszanin z grupy antacida. II. Wplyw temperatury na powstawanie hydrotalcytu w zawiesinach zobojetniajacych.

Eight antacid mixtures were stored for 110 days at 25 degrees C, 35 degrees C and 45 degrees C in the form of suspensions in water. Changes in pH were followed, and the structural changes in suspension components were studied by X-ray analysis. It has been stated that formation of hydrotalcite, the product od interaction of the mixture components depends mainly on the kind and ratio of the suspension reactants, and only to a little degree on the storage temperature.

[Drug interactions during storage of mixtures of the antacid group. III. Effect of relative humidity on structural changes in mixtures aluminum hydroxide gel and magnesium hydroxide in the solid phase]. / Badanie oddzialywan zachodzacych podczas przechowywania mieszanin z grupy antacida.III. WpLyw wilgotnosci wzglednej na zmiany struktury mieszanin zelu wodorotlenku glinowego i magnezowego w fazie staLej.

Mixtures of A1(OH)3 gel and Mg(OH)2 were stored for 14 months in the solid phase in chambers with relative air humidity of 35%, 55%, 76% and 92%. IR spectra of the stored mixtures were measured. In mixtures stored at relative air humidity of 35% there were found no changes in IR spectra, while the mixtures stored at relative air humidity of 92% proved to exhibit IR spectra characteristic for hydrotalcite.

[Study on the interactions during storage of compounds of the antacid group. I. Interactions of the components in suspensions]. / Badanie oddzialywan zachodzacych podczas przechowywania mieszanin z grupy antacida. I. Oddzialywania miedzy skladnikami mieszanin w zawiesinie.

Twenty antacid mixtures of six quality groups containing Al(OH)3, gel, Mg(OH)2, Mg2Si3O8, CaCO3 and NaAl(OH)2CO3 at different ratios were prepared and stored for 150 days at 20 degrees C in the form of aqueous suspensions. Changes of pH in the suspensions were measured, and the accompanying structural changes were examined by IR spectrometry and X-ray diffraction analysis. Hydrotalcite was found to be formed during storage of aqueous suspensions of mixtures of Al(OH)3 Mg(OH)2; Al(OH)3: Mg(OH)2: CaCO3; Al(OH)3: Mg(OH)2: NaAl(OH)2CO3 and Mg(OH)2: NaAl(OH)2CO3. Initial neutralization activities of the suspensions and those found after the storage were compared.

Effect of composition on the neutralizing properties of antacid preparations.

11 antacid mixtures made up to simulate the preparations available on the market were prepared. These mixtures contain aluminium hydroxide gel, calcium carbonate, magnesium hydroxide and magnesium trisilicate. The antacid properties of the mixtures obtained were characterized by total acid consuming capacity, rate of neutralization and duration of action. It was indicated that the composition of the mixtures influenced their neutralizing properties; an interaction between constituents of these preparations was noted.