Study on the Inclusion Interactions of β‐Cyclodextrin and Its Derivative with Clomipramine by Spectroscopy and Its Analytic Application

Abstract

The inclusion interactions of β‐cyclodextrin (β‐CD) and its derivative, namely hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) with clomipramine (CLOM) have been investigated. The guest molecule was clomipramine and inclusion complexes were characterized by UV, ¹H NMR, ¹³C NMR, and 2D NMR spectroscopy. The main factors affecting the inclusion interaction were discussed in detail. The inclusion complexation behaviour of cyclodextrins with clomipramine was studied in an aqueous buffer solution of pH 4 and pH 5 at room temperature. According to the continuous variation method (Job's plot) applied to spectroscopy measurements a 1∶1 stoichiometry has been proposed for the complexes. Based on the significant enhancement of absorption intensity of clomipramine, a sensitive UV spectrophotometric methods with high sensitivity and selectivity were developed for determination of substance in bulk aqueous solution in the presence of β‐CD and HP‐β‐CD. The apparent association constant of the complex was 9.42 · 10³ mol⁻¹ L and 9.58 · 10³ mol⁻¹ L and the linear range was 17.6–70 µg mL⁻¹ with a correlation coefficient of 0.9997 and a relative standard deviation (R.S.D.) of 0.97% and 1.02% using β‐CD and HP‐β‐CD, respectively. There was no interference from the excipients normally used in tablets and capsules. The proposed methods were successfully applied to the analysis of clomipramine in pharmaceuticals with satisfactory results.

Keywords:

• Cyclodextrin
• clomipramine
• spectroscopy
• formulations