Oral controlled release of melatonin using polymer-reinforced and coated alginate beads

Abstract

Melatonin (MT) is an indole amide pineal hormone. The sustained release dosage form which delivers MT in a circadian fashion over 8 h is of clinical value, because of its short half-life, for those who have disordered circadian rhythms. The purpose of this study was to prepare polymer reinforced and coated alginate beads and to evaluate in vitro release characteristics in simulated gastric and intestinal fluids, varying drug loadings, and the amount of polymer and plasticizer. The Eudragit® RS100 as a polymer and aluminium tristearate (AT) as a plasticizer were used, respectively. Plain (simple) alginate beads were prepared by dropping the mixture of MT and sodium alginate into 0.2 M CaCl2 solution. The polymer reinforced alginate beads were prepared by dropping the mixture of drug, sodium alginate and polymer with plasticizer into 0.2 M CaCl2 solution. The coated alginate beads were also prepared by adding plain alginate beads into polymer solution using the solvent evaporation method. Acetone was used as a solvent of polymer. The dissolution test was carried out using the basket method at a stirring speed of 100 rpm at 37°C in simulated gastric (pH 1.4) and intestinal fluid (pH 7.4). The concentration of MT was determined by reverse phase HPLC. In the study of scanning electron microscope (SEM), the surface crystal and roughness were reduced by polymeric reinforcing and coating alginate beads. However, higher coatings of alginate beads resulted in cracks and holes on the surface of coated alginate beads. The longer curing time into 0.2 M CaCl2 solution, the lower trapping efficiency of MT was observed due to release of MT during gelling process. The release rate of MT in gastric and intestinal fluid when drug loading increased was not changed. The polymeric reinforcement of alginate beads on the release rate of MT was not significant in gastric fluid, but pronounced in intestinal fluid with initial burst out release for 1 h. The release rate of the drug from coated alginate beads was retarded, both in gastric and intestinal fluid when compared to plain alginate beads. As the polymer contents increased, the release rate was significantly decreased in the intestinal fluid due to hindrance of swelling and disintegration of coated alginate beads unlike gastric fluid. The release rate of drug from coated alginate beads was more efficiently sustained in the gastric and intestinal fluid when 0.1 g of AT as a plasticizer was used for coating. However, the higher amount of AT was not useful for retarding the release rate. From the current studies, the sustained release formulation of MT using alginate beads may provide as an alternative for oral delivery of MT.