Resveratrol-loaded calcium-pectinate beads: Effects of formulation parameters on drug release and bead characteristics

Abstract

Resveratrol has potential therapeutic efficacy on several lower gastro-intestinal (GI) diseases such as colitis and colorectal cancer. But resveratrol is quickly absorbed and metabolized at the upper GI tract, which renders it unsuitable for this purpose. This study aimed at devising a delayed release formulation of resveratrol as calcium-pectinate (Ca-pectinate) beads and investigated the impact of various formulation parameters on bead characteristics. Ca-pectinate beads were prepared by varying six formulation parameters (cross-linking pH, cross-linker concentration, cross-linking time, drying condition, pectin concentration, and resveratrol concentration). Their effects were investigated on calcium entrapment, moisture content and weight loss during drying, particle shape and size, resveratrol entrapment and loading efficiency, swelling–erosion, and resveratrol retention pattern of formulated beads. Preparative conditions were optimized from these studies and optimized beads were further subjected to morphological examination, drug–polymer interaction, and enzymatic degradation study. Almost all prepared beads were spherical with ∼1 mm diameter. Swelling–erosion and drug retention pattern were changed with formulation variables. Release data of almost all beads showed linearity of the plots for the cumulative percent resveratrol released versus square root of time often after an initial lag period. Observations from the present study revealed that optimized Ca-pectinate beads can encapsulate a very high amount of resveratrol (>97.5%) and can be used for delayed release and site-specific delivery to the lower GI tract. Depending on the formulation parameters, release of resveratrol after 10 h incubation in the intestinal media was 80–100%. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:840–860, 2010