TITLE:
Improvement of Dissolution Rate of Gliclazide Using Solid Dispersions with Aerosil 380 and Its Effect on Alloxan Induced Diabetic Rats
AUTHORS:
Subrata Paul, Md. Nur Islam, Md. Ashraf Ali, Ranjan Kumar Barman, Mir Imam Ibne Wahed, Bytul M. Rahman
KEYWORDS:
In-Vitro Dissolution, Fumed Silica, Solid Dispersions, Gliclazide, Alloxan, Diabetes
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.10 No.8,
August
22,
2019
ABSTRACT: The main objective of this research
is to conduct a comprehensive study for enhancing the aqueous solubility of
poorly water soluble gliclazide using
hydrophilic fumed silica particles (Aerosil® 380) and evaluating the
influence of silica on drug release profile and pharmacological activity on alloxan induced diabetic rats. Solid dispersions
(SD’s) of gliclazide were prepared using solvent
evaporation method. The dissolution profiles and solid state characterization of the SD’s prepared were all
evaluated. The dissolution rate of gliclazide in the SD’s with fumed silica
(weight ratio, 1:1) was approximately 38%, which is about 10 fold higher than
that of the pure drug after 30 min. After forming the SD’s, gliclazide changed
into an amorphous state, which can infer from differential scanning calorimetry
(DSC) and powder X-ray diffraction (PXRD). Fourier transform infrared
spectroscopy (FTIR) also revealed the formation of weak hydrogen bonding
through the interactions between the secondary amine groups of gliclazide and
silanol groups of silica particles in the SD’s. The rapid dissolution rate from
the SD’s might be attributed to the amorphization of drug, improved specific surface area and wettability than the original drug crystals. Further, we
investigated the antidiabetic effects of SD’s of gliclazide in alloxan induced diabetic rats. The SD’s of
gliclazide decrease the blood glucose level 64% whereas the conventional
gliclazide decreases only 37% in diabetic rats. Lipid profiles, kidney and liver
functions are remarkably improved in diabetic rat treated with SD’s of
gliclazide than that of conventional gliclazide. These results suggest that
SD’s of gliclazide have much more bioavailability and hence are more
pharmacologically active than that of conventional gliclazide form.