Preparation and characterization of melatonin-loaded stearyl alcohol microspheres

Abstract

A sustained release dosage form which delivers melatonin (MT), a pineal hormone, is of clinical value because of the short half-life of MT, for those who have a disordered circadian rhythm. The purpose of this study was to prepare MT-loaded microspheres by the emulsion melting/cooling method using stearyl alcohol (SA) and also dual walled chitosan and sodium alginate beads, and to evaluate the release characteristics in simulated gastric and intestinal fluid. The MT-loaded microspheres were spherical, ranging in diameter from about 250–750µm. When polyethylene glycol 4000 (PEG), as a water-soluble or aluminium tristearate (AT), as a water-insoluble additive, was incorporated, the surface roughness was further reduced resulting in a smooth matrix structure. The dual walled chitosan and sodium alginate beads entrapping small MT-loaded microspheres were not spherical in structure. As the additives incorporated into SA microspheres increased, the drug content decreased. The release profiles of the MT-loaded microspheres were independent of pH. When the melted SA solution was cooled rapidly in 10 min to 25 °C, the drug content increased but the release rate of MT-loaded microspheres decreased. The release rate of drug decreased as the amount of SA increased but an increase of agitation speed and amount of AT and PEG resulted in increased release rates. The release rate of drug from dual walled chitosan beads increased slightly but was retarded in the case of dual walled alginate beads when compared to MT-loaded microspheres. The emulsion melting/cooling method used to prepare MT-loaded microspheres using SA is simple and inexpensive, and may provide an alternative for the preparation of an oral sustained release dosage form of MT without using harmful organic solvents. The dual walled chitosan and sodium alginate beads may also provide a convenient way to control the release of drugs.

Key Words:

• Melatonin
• stearyl alcohol
• microspheres
• dual walled beads
• surface morphology
• release rate
• chitosan
• sodium alginate