A simple and cost-effective synthesis of sulfated β-cyclodextrin and its application as chiral mobile phase additive in the separation of cloperastine enantiomers

Abstract

A simple and cost-effective method for the synthesis of sulfated β-cyclodextrin, one of the most widely used chiral mobile phase additives, using sulfamic acid as a sulfonating agent has been described. The method was optimized, and the synthesized product was characterized by spectroscopic, size-exclusion chromatographic, thermal, and microscopic methods and was compared to the marketed Sigma Aldrich sulfated β-cyclodextrin. β-Cyclodextrin, hydroxypropyl β-cyclodextrin, sulfated β-cyclodextrin (marketed and synthesized) were evaluated as chiral mobile phase additives for the enantiomeric separation of cloperastine, an antitussive agent, using reversed-phase HPLC. Under optimized conditions, a resolution of 3.14 was achieved within 15 min on an achiral Kromasil C₈ (150 × 4.6 mm, 5 µm) column, with 5 mM monopotassium phosphate containing 10 mM synthesized sulfated β-cyclodextrin pH 3.0 and 45% methanol as mobile phase. The method utilizing synthesized sulfated β-cyclodextrin as chiral mobile phase additive was validated as per ICH guidelines and applied for the quantitative determination of cloperastine enantiomers in active pharmaceutical ingredients and pharmaceutical formulations. The selectivity changes imparted by sulfated β-cyclodextrin were proven to be beneficial for chiral separation. For the enantiomeric separation of cloperastine, synthesized sulfated β-cyclodextrin afforded better resolution than marketed sulfated β-cyclodextrin.