Study on the formation of cyclodextrin and thiobarbiturate complexes

The aim of this M.Sc. study was to increase transport ability of 5-substituted-1-(o-aryl)-2-thiobarbituric acids in aqueous media by complexing them with cyclodextrin. Many derivatives of barbituric and thiobarbituric acids are drugs that act as central nervous system antidepressants and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. Cyclodextrins have been called as cyclic oligosaccharides that can react with different molecules and form complex compounds. They are used to improve drug solubilization in aqueous medium. Therefore they have found many applications as pharmaceutical excipients. In this study, first of all o-substituted-2-thiobarbituric acid derivatives were synthesized from the corresponding o-substituted phenylthioureas. After that thiobarbituric acid and cyclodextrin derivatives were complexed in different solvents such as distilled water and phosphate buffer. Several factors were investigated for their effects on the complexation rate. One of them is thiobarbituric acid (TBA):cyclodextrin (CD) ratio. One derivative 5-methyl-1-(o-fluorophenyl)-2-thiobarbituric acid was found to have the highest solubility in distilled water and phosphate buffer when TBA:CD ratio is 1:4 at the studied temperatures 25ºC and 37ºC. Another derivative, 5,5-dimethyl-1-(o-tolyl)-2-thiobarbituric acid has been found to have the highest solubility in distilled water when TBA:CD ratio is 1:1 at 25°C and 37°C. In phosphate buffer, highest concentration of TBA can be obtained at 25°C when TBA:CD ratio is 1:2, and at 37°C highest concentration of TBA was obtained, when TBA:CD ratio is 1:1. The effect of the structure of cyclodextrin on the complexation was also studied by using two cyclodextrin derivatives. Among them, β-CD causes to form a more stable complex than 2-hydroxypropyl-β-CD. Additionally, temperature effect was studied and it has been observed, that the complexation rate is higher at 25ºC than that at 37ºC. Results related to temperature effect study were also used to calculate the standard free energy change (ΔGº), the standard enthalpy change (ΔHº) and the standard entropy change (ΔSº) values for complexation process.