The application of cyclomaltoheptaose (/3-cyclodextrin, /3CD) in the pharmaceutical field is limited by its relatively low aqueous solubility. Many kinds of branched CDs have been studied' because they are significantly more soluble in water than the natural CDs, and some have found pharmaceutical applications particularly in injection preparations 2,3. We now report on the complexation of the vasodilator (coronary) glycerol trinitrate (nitroglycerin, TNG) with 6-O+ maltosyl-p-cyclodextrin (G&D) in comparison with the complexation of pCD4,5 and other PCD derivative@.
The formation of a complex between TNG and G,-PCD in aqueous solution was studied using the solubility method. Fig. 1 shows an equilibrium-phase solubility diagram obtained for the TNGIG,-PCD system at 5". The plot shows a typical AL-type solubility curve [cf the B,-type curve for the TNGIBCD system4s5 and the A,-type curve of the TNG/water-soluble /3CD polymer (CDPS) system6]. The apparent stability constant (K') of the TNGIG#CD system, assuming that a 1: 1 complex was formed, was 67.95 M-l at 5" (cf. 29.4 M-' for the TNG/CDPS complex, and 181 M-~ for the TNGIPCD complex).
'H-N.m.r. techniques were used to elucidate the interactions of TNG/G,-PCD in aqueous solution (see Table I). On complexation, four signals of TNG were shifted to higher field and two were shifted to lower field. The chemical shift data were similar for the TNG/G,-PCD and TNG/fiCD systems, and suggest that the TNG molecule is included partially in the cavity of G&D and /3CD.