Design and development of gliclazide mucoadhesive microcapsules: in vitro and in vivo evaluation

Abstract

In this study an attempt was made to prepare mucoadhesive microcapsules of gliclazide using various mucoadhesive polymers designed for oral controlled release. Gliclazide microcapsules were prepared using sodium alginate and mucoadhesive polymer such as sodium carboxymethyl cellulose (sodium CMC), carbopol 934P or hydroxy propylmethyl cellulose (HPMC) by orifice-ionic gelation method. The microcapsules were evaluated for surface morphology and particle shape by scanning electron microscope. Microcapsules were also evaluated for their microencapsulation efficiency, in vitro wash-off mucoadhesion test, in vitro drug release and in vivo study. The microcapsules were discrete, spherical and free flowing. The microencapsulation efficiency was in the range of 65-80% and microcapsules exhibited good mucoadhesive property in the in vitro wash off test. The percentage of microcapsules adhering to tissue at pH 7.4 after 6 h varied from 12-32%, whereas the percentage of microcapsules adhering to tissue at pH 1.2 after 6 h varied from 35-68%. The drug release was also found to be slow and extended for more than 16 h. In vivo testing of the mucoadhesive microcapsules in diabetic albino rats demonstrated significant antidiabetic effect of gliclazide. The hypoglycemic effect obtained by mucoadhesive microcapsules was for more than 16 h whereas gliclazide produced an antidiabetic effect for only 10 h suggesting that mucoadhesive microcapsules are a valuable system for the long term delivery of gliclazide.

Fig. 1

The effect of microcapsule formation time on drug loading efficiency

Fig. 2

Scanning electron micrographs of gliclazide microcapsules

Fig. 3

Particle size distribution plot for gliclazide microcapsules for batch MC7 and MC8

Fig. 4

FTIR spectra of microcapsule batch MC3, gliclazide, microcapsule batch MC1 and microcapsule batch MC2

Fig. 5

In vitro release profile of gliclazide mucoadhesive microcapsules of various batches

Fig. 6

In vitro release profile of gliclazide mucoadhesive microcapsules of batch MC—MC7 and MC8 in phosphate buffer pH 7.4 and 0.1 N HCl pH 1.2

Fig. 7

Comparative in vivo study of gliclazide microcapsules of batch MC7 and MC8 with pure glicalzide and marketed gliclazide tablet