Effect of water-soluble polymers and cosolvent on with candisartan– cyclodextrin complex solubility


Objective: The aim of the study is to find the candesartan celexitile (CC) solubility profile in thepresence of ß-cyclodexrin, poloxamer 188 and PEG 400 and the synergism effect of the cosolvencyof PEG 400 and the solubilizing effect of polymer poloxamer 188 on the drug cyclodextrincomplex.Methods: An excess amount of (CC) was added to 10 mL aqueous solutions containing rangeconcentrations of either poloxamer 188 (0−0.4% w/v), β-CD (0−1%, w/v) or PEG (0−50%,v/v) at25±1 ºC separately. The mixtures of aqueous solution were shaken in a thermostated water bath at25°C ± 2 for 24 h to reach equilibrium. After that, all the suspensions were filtered through 0.22 μmsyringe filter and assayed for (CC) by UV Spectrophotometer at ʎ of 255 nm. Phase solubilitydiagrams were plotted with (CC) solubility versus either ß-CD, poloxamer or PEG 400concentration separately.Results: It was found that the solubility of (CC) increased with the increasing concentration ofpoloxamer188, PEG 400 or ß-CD. The phase solubility curves of (CC) in aqueous solution at 25°Cof ß-CD was of Higuchi’s AL-type confirming the formation of 1:1 complexes. The synergismeffect of poloxamer 188 and PEG 400 on the solubility of (CC) in the presence ß-CD was marked.The values of stability constants (Ksp) of drug- ß-CD complexes and in the presence of PEG 400 orpoloxamer 188 with 0.4 mg / ml ß-CD were 59.7, 5.8 and 195.8 M-1 respectively. Addition ofpoloxamer 188 to the drug-ß-CD complex increase the constant stability while addition of PEG 400decrease the constant stability of the complex.Conclusion: The solubility profile of (CC) in the presence of CD followed Higuchi equationconfirming the formation of 1:1complexes of AL-type. The synergism effect of the polymer on theCC-CD complexes was significant.