Effect of inorganic salts on the inclusion complex formation and solubilizing potency of cyclodextrins

The competition of hydrophobic molecules for the cyclodextrin (CD) cavity is well known and reported in the literature. However, it is not so trivial, how inorganic salts, small cations and anions may affect the inclusion complex formation, and thereby the functional properties of CDs. This topic is recently of particular interest for formulators since there are several granted patents and published patent applications on commercially available CD derivatives with certain intrinsic ion contents (in particular chloride and phosphate), such as US patents US7635773, US8410077, US9200088, US9493582 as well as US patent applications US2015284479 and US2015045311. All these documents highlight that the absence of these ions is specifically favored. On the other hand, the patent disclosing the SBE-BCD-based amiodarone formulation (US6869939) states that the advantage of using SBE-BCD is that a wider range of buffers was found compatible compared to other known (surfactant-containing) amiodarone-containing liquid formulations. Suitable buffering agents were enumerated such as phosphate and borate. In Example 10 of patent US6869939, a suitable formulation containing amiodarone HCl (50 mg/mL) in a solution containing 114 mM monobasic sodium phosphate and 30% w/v SBE-BCD is illustrating the advantageous use of phosphate ions in a SBE-BCD based formulation.