Preparation of calcium alginate-tetrandrine beads using ionic gelation method as colon-targeted dosage form

Abstract

Colon drug delivery systems are widely used to deliver active substances and provide better therapeutic effects to the site of disease in the colon, i.e., treatment for intestinal fibrosis. In this study, we aimed to formulate tetrandrine into calcium-alginate beads coated by Hydroxypropylmethyl Cellulose Phthalate (HPMCP), Cellulose Acetate Phthalate (CAP), Eudragit L100-55 or Eudragit L100 as colon targeted dosage to provide better antifibrosis effect at the site of disease. Among dosage forms, beads provide some advantages for colon drug delivery system, especially for its flexibility in dosing. Calcium alginate-tetrandrine beads were prepared in three formulae with various concentrations of calcium chloride as a crosslinking agent (2%, 3%, and 4%). All formulae were characterized by its morphology, particle size, moisture content, process yield, entrapment efficiency, thermal character, crystallinity, and swelling. The obtained beads possessed almost spherical and particle size distribution of 742.753-780.683 μm. Formula 2, with a ratio of sodium alginate and CaCl2 2:3, showed the best entrapment efficiency of 82.46 ± 2.73%. Formula 2 was then coated with HPMCP HP-55, CAP, Eudragit L100-55 or Eudragit L100 and measured for its drug release profile invitro. The results showed that the beads which were coated with 10% CAP were able to hold the drug released in the gastric and provide better released of tetrandrine in the colon condition (67.68%). This result also confirmed with the in-vivo test. Beads which were coated by CAP 10% could be found in the rat intestine.