Colon targeted beads loaded with pterostilbene: Formulation, optimization, characterization and in vivo evaluation

Pterostilbene has a proven chemopreventive effect for colon carcinogenesis but suffers low bioavailability limitations and therefore unable to reach the colonic tissue.

To overcome the issue of low bioavailability, pterostilbene was formulated into an oral colon targeted beads by ionic gelation method using pectin and zinc acetate. Optimization was carried out by 2³ factorial design whereby the effect of pectin concentration (X ₁), zinc acetate concentration (X ₂) and pterostilbene:pectin ratio (X ₃) were studied on entrapment efficiency (Y ₁) and in vitro drug release till 24 h (Y ₂). The optimized beads were characterized for shape and size, swelling and surface morphology. The optimized beads were uniformly coated with Eudragit S-100 using fluidized bed coater. Optimized coated beads were characterized for in vitro drug release till 24 h and surface morphology. Pharmacokinetic and organ distribution study were performed in rats to ascertain the release of pterostilbene in colon.

The optimized formulation comprised of 2% w/v of pectin concentration (X ₁), 2% w/v of zinc acetate concentration (X ₂) and 1:4 of pterostilbene:pectin ratio (X ₃), which showed a satisfactory entrapment efficiency (64.80%) and in vitro release (37.88%) till 24 h. The zinc pectinate beads exhibited sphericity, uniform size distribution, adequate swelling and rough surface. The optimized coated beads achieved 15% weight gain, displayed smooth surface and optimum drug release. Pterostilbene from optimized coated beads appeared in the plasma at 14 h and reached the C_max at 22 h (T_max), whereas plain pterostilbene exhibited T_max of 3 h.

Thus, larger distribution of pterostilbene was obtained in the colonic tissue compared to stomach and small intestinal tissues. Thus, delayed T_max and larger distribution of pterostilbene in colonic tissue confirmed the targeting of beads to colon.