PREPARATION & IN-VITRO EVALUATION OF INCLUSION COMPLEXES OF SIMVASTATIN TABLET WITH CYCLODEXTRINS
Vijay Chandrakant Kute* and Ganesh Godge
ABSTRACT
In the present study, the practically insoluble drug simvastatin (SV)
and its inclusion complex with hydroxypropyl β-cyclodextrin (HP-β-
CD) prepared using different process were investigated to improve the
aqueous solubility and the dissolution rate of drug, thus enhancing its
bioavailability. Inclusion complexation in aqueous solution and solid
state was evaluated by the phase solubility diagram, differential
scanning calorimetry (DSC), powder X-ray diffractometry (PXRD),
Fourier-transform infrared spectroscopy (FT-IR) and scanning electron
microscopy (SEM). The phase solubility diagram with HP-β-CD
was classified as type A indicating the formation of 1:1
stoichiometric inclusion complex. The apparent complexation
constants (K1:1) calculated from phase solubility diagram were 103
and 105 Mat-1 25oC. No characteristic diffraction peaks corresponding
to SV was observed for the inclusion complex in PXRD. Complex shows resulting in the
formation of amorphous form. Aqueous solubility and dissolution studies indicated that the
dissolution rates were remarkably increased in inclusion complex, compared with the
physical mixture, Kneading and drug alone. This could be primarily attributed to the
improved solubility and dissolution associated with inclusion complex between drug and HP-
β-CD. In conclusion, spray drying process could be a useful method for the preparation of the
inclusion complex of drug with HP-β-CD and its solubility, dissolution rate and
hypolipidemic activity were significantly increased by complexation between SV and HP-β-
CD.
Keywords: Simvastatin; Hydroxypropyl-?-cyclodextrin; Inclusion complex; Spray drying process.
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