PREPARATION AND INVESTIGATION OF INCLUSION COMPLEXES OF
ALKYL CARBONATE DERIVATIVES OF -CYCLODEXTRIN:
PRELIMINARY RESULTS
Roberta Cavalli1, Francesco Trotta2 and Michele Trotta1
1. Dipartimento di Scienza e Tecnologia del Farmaco - Università di Torino - Via Pietro Giuria 9,
I-10125 Torino – Italy.
2. Dipartimento di Chimica IFM - Università di Torino - Via Pietro Giuria 7, I-10125 Torino –
Italy.
A series of alkyl carbonates (ethyl, butyl and hexyl) of -cyclodextrin (CD) was
prepared by reacting the corresponding activated alcohol with -CD in anhydrous
DMF at 80°C. The -CD derivatives obtained were characterized by TLC and FT- IR
analyses.
The haemolytic behaviour of the three alkyl carbonate -CDs was studied,
determining their haemolitic effect on erithrocytes at 37°C. The three alkyl carbonate
 CDs had a less marked haemolytic effect than the parent -CD.
Three poorly-soluble drugs with different structures, namely flurbiprofen,
progesterone and diazepam, were chosen as models to evaluate the complexation
capability of the three alkyl carbonate -CDs; inclusion complexes were obtained
using the co-precipitation method, and characterised by differential scanning
calorimetry (DSC) and X-ray powder diffractometry (RX) analyses.
The DSC thermograms of the drug-alkyl carbonate -CD complexes did not show
melting peaks corresponding to the fusion of the three drugs, indicating the formation
of inclusion compounds. This was confirmed by the RX analyses.
The binding constants of the three drugs with the three alkyl carbonate -CDs were
determined by the phase-solubility method. The influence of several parameters, such
as pH, temperature and degree of substitution, was also studied. As control, the parent
-CD was used.
Binding capacities were related to alkyl chain length and to the guest molecule.
Water solubility of the three drugs increased in the presence of the -CD derivatives
versus their solubility in water alone.
In conclusion, the three alkyl carbonate derivatives of -cyclodextrin can be proposed
for the purpose of improving aqueous solubility or chemical stability of drugs in
pharmaceutical technology.