COMPLEXATION OF DIHYDROERGOTAMINE MESYLATE WITH CYCLODEXTRIN DERIVATIVES - SOLUBILITY AND STABILITY IN AQUEOUS-SOLUTION

2-Hydroxypropyl-beta-cyclodextrin (2HP-beta-CyD) and 2,6-di-O-methyl-beta-cyclodextrin (DIMEB) were tested as solubilizing agents for dihydroergotamine mesylate, with the aim of improving the pharmacotechnical properties of this drug. The pH dependence of the complexation was investigated on the basis of solubility/pH profiles. For uncomplexed dihydroergotamine mesylate, the solubility increased sharply in the acidic range. The same pH dependence was observed for 2HP-beta-CyD and DIMEB. The shape of the pH profiles was not altered, but the pH profiles occurred at considerably higher concentrations than for dihydroergotamine mesylate alone. The solubilizing effect clearly increased in the acidic range, and the effects were stronger for DIMEB than for 2HP-beta-CyD. The maximum stability of dihydroergotamine mesylate was shown to be pH 4.0. The degradation rates of dihydroergotamine mesylate in beta-CyD solutions are not very different from those in pure dihydroergotamine mesylate solution. DIMEB has the most favourable effect on the stability, while 2HP-beta-CyD causes higher degradation. During autoclaving, however, dihydroergotamine mesylate was to some extent protected against degradation by 2HP-beta-CyD complexation. Nevertheless degradation was so strong that autoclaving is not possible.