The work reported by Enrico Redenti and Laura Ribeiro states that hydroxy acid increases the complexation efficiency of beta-cyclodextrin. They have prepared ternary (Drug/CD/Hydroxy acid) and quaternary (Drug/CD/Hydroxyacid/Hydrophilic polymer) inclusion complexes and found promising dissolution results. However, it is unclear that how much amount of hydroxy acid must be used for preparing this complex. There are some reports where the authors have used drug, CD and hydroxy acid in the molar ratio 1:1:0.5, whereas some have used 1: 1:1. But, on what basis this has been decided is still an unanswered question for me. Increasing the amount of citric acid will ionize the drug (off course the above mentioned complexes are related to the poorly soluble weak bases) and consequently dissolve it. The phase solubility study and Jobs plot help us to decide the molar ratio of drug and CD. I want to know that how to decide the number of moles of hydroxy acid (e.g. citric acid) that will be required for preparation of a ternary complex if we are preparing drug:CD complex in 1:1 molar ratio.

Ref:

1. Redenti et al. Drug/cyclodextrin/hydroxy acid multicomponent systems. Properties and pharmaceutical applications. J. Pharm. Sci. Vol. 89, 1–8 (2000).

2. Ribeiro et al. Multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers monitored by NMR and solubility studies. European Journal of Pharmaceutical Sciences Vol. 24, 1–13 (2005).