Investigation Of Inclusion Complexation, Chemical Modification And Microemulsion Formulation Of Curcumin For Enhanced Antibacterial Property
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Date
2015-04
Authors
KHALID, SYED HAROON
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Abstract
The aim of this study was to investigate the effect of solubility enhancement,
chemical modification and microemulsion formulation on antibacterial property of
curcumin. Prior to the study, a stability indicating, simple and sensitive HPLC-UV
method was developed to quantify curcumin concentration in Curcuma longa extract.
For solubility enhancement, β-cyclodextrin (βCD) and its derivative hydroxypropyl-
β-cyclodextrin (HPβCD) were used to prepare curcumin inclusion complex using
kneading method. The inclusion complexes were examined using Fourier transformed
infrared (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction
(XRD) and scanning electron microscopy (SEM). Based on DSC and XRD results,
Nuclear magnetic resonance (NMR) study was performed to investigate the inclusion
complex formation. For chemical modification method, curcumin-Ag(I) complex was
synthesized by replacing the phenolic protons of curcumin with sodium followed by
silver ions as well as coordination of carbonyl groups to the silver metal center. The
metal complex was characterized using FT-IR and FT-NMR spectroscopy. For
microemulsion formulation, solubility studies of curcumin in different oils,
surfactants, co-surfactants and surfactant-cosurfactant mixture, were performed.
Pseudoternary phase diagram was constructed to identify the microemulsion region.
The microemulsion formulations were evaluated for pH, viscosity, conductivity,
particle size, polydispersity index, zeta potential, curcumin content and in-vitro
release. The final ME formulation was used for stability (at 26 ± 2 ºC/ 55 % RH and
40°C/75% RH for 6 months) studies. The inclusion complex (Cur-HPβCD), metal
complex (curcumin-Ag(I)) and microemulsion formulation (curcumin loaded) were
evaluated for the antibacterial properties. The HPLC-UV method showed good
recovery, accuracy and precision with short run time of less than 7 min. The inclusion
complexation increased the solubility, dissolution and antibacterial activity of Cur-
HPβCD. HPβCD produced higher curcumin solubility and dissolution than that of
βCD. DSC thermograms of Cur-HPβCD showed a decrease in the intensity of
endothermic peak of curcumin more than Cur-βCD. XRD results indicated that
curcumin shifted to amorphous state when complexed with HPβCD but retained its
crystalline nature with βCD. NMR study showed the inclusion complex formation.
FTIR and 13C spectra of curcumin-Ag(I) indicated the significant changes in support
of formation of the proposed complex. NMR studies confirmed the Ag attachment to
the curcumin structure. Isopropyl myristate (IPM), Tween 80, PEG 400 were chosen
to prepare microemulsion formulations. The microemulsion region was identified
with the aid of ternary phase diagram. Seven formulations were selected from the
microemulsion area. The final selected microemulsion formulation loaded with
curcumin was stable after storage for six months. Cur-HPβCD inclusion complex was
more active against both S. aureus and E. coli, when compared with curcumin,
indicating that higher water solubility and dissolution of Cur-HPβCD led to increased
antibacterial activity of curcumin. Curcumin-Ag(I) complex did not demonstrate
antibacterial activity against bacteria tested. Microemulsion formulation was found to
enhance curcumin antibacterial activity against the growth of S. aureus and E.coli. In
conclusion, inclusion complexation and microemulsion formulation could be used to
enhance activity of curcumin, via an increase in the solubility of curcumin.
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Keywords
Investigation Of Inclusion Complexation, Chemical Modification And Microemulsion Formulation , Of Curcumin For Enhanced Antibacterial Property