Effect of Temperature on Cyclodextrin Production and Characterization of Paracetamol/Cyclodextrin Complexes
Jarunee Kaulpiboon PhD*, Prakarn Rudeekulthamrong PhD**
Affiliation : * Department of Pre-Clinical Science (Biochemistry), Faculty of Medicine, Thammasat University, Pathumthanee, Thailand ** Department of Biochemistry, Phramongkutklao College of Medicine, Bangkok, Thailand
Objective : To compare the effect of different reaction temperatures on the cyclization and coupling reactions of the Toruzyme®
CGTase influencing the yield of cyclodextrins (CDs) and to study the solubility of paracetamol with CDs.
Material and Method: Type and amount of CDs were analyzed by HPAEC-PAD. The stability constants for the inclusion
complex formed between CDs and paracetamol were determined using the phase solubility method. The solubility of paracetamol
with CDs was measured by UV-spectrophotometer at 240 nm.
Results : The result has shown that the reaction temperature has effect on the Toruzyme® CGTase reactions in production of
CDs. The CDs yield after 30 min of incubation was higher at 60°C than at 80°C. The catalytic efficiency (kcat/Km) of this enzyme
indicated the higher value of the cyclization reaction at 60°C compared to 80°C while the opposite was found for the coupling
reaction. Paracetamol is used as an analgesic and antipyretic but it is poorly water-soluble drug. To improve the solubility of
paracetamol, CDs obtained were used to study for paracetamol/CDs complexes. The phase-solubility diagrams of paracetamol
with α-, β- and γ-CD were AN type while that of paracetamol with maltosyl-β-CD (G2-β-CD) complex was AL type. The
stability constants (Kc) for the inclusion complex of paracetamol with α-, β-, γ-CD and G2-β-CD were 5.69, 16.75, 4.73 and
2,223.25 M-1, respectively.
Conclusion : The optimum temperature for CDs production was at 60°C and the low solubility of paracetamol was signifi-
cantly improved by complexation with CDs, where the enhancing effect was in the order of G2-β-CD > β-CD > α-CD > γ-
CD.
Keywords : Cyclodextrin, G2-β-CD, Paracetamol, Phase solubility, Stability constant
