Jet lag treatment with controlled release melatonin and caffeine

Multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine was designed to restore jet lag sleep-wake cycle. The polymeric pellets were produced using extrusion-spheronization technique and fluid-bed coated when applicable. The compact and Dome module were produced by compressing pellets with cushioning agent. Dome matrix was assembly of modules with pre-determined compact formulation and drug release characteristics. The physicochemical and in vivo pharmacokinetics of delivery systems were examined.

Highlights
• Compact of pure cellulosic pellets sustained but enabled full melatonin release.

• Compact of alginate-chitosan pellets with high viscosity fillers delayed caffeine release.

• High viscosity HPMC and EC fillers delayed initial and late caffeine dissolution respectively.

• Substantial caffeine was released against colonic fecal content that digested the pellets.

• Dual drug and release kinetics of Dome matrix provide sleep-wake cycle for jetlag treatment.

Melatonin loaded alginate/chitosan-less matrix exhibited full drug release within 8 h gastrointestinal transit with low viscosity hydroxypropymethylcellulose as cushioning agent. The cushioning agent reduced burst drug release and omission of alginate-chitosan enabled full drug release. Delayed-release alginate-chitosan caffeine matrix was not attainable through polymer coating due to premature coat detachment. Admixing of cushioning agent high viscosity hydroxypropylmethylcellulose and high viscosity ethylcellulose (9:1 weight ratio) with coat-free caffeine loaded particulates introduced delayed-release response via hydroxypropylmethylcellulose swelled in early dissolution phase and ethylcellulose sustained matrix hydrophobicity at prolonged phase. The caffeine was released substantially in colonic fluid in response to matrix polymers being degraded by rat colonic content. Dome matrix with dual drug release kinetics and modulated pharmacokinetics is produced to introduce melatonin-induced sleep phase then caffeine-stimulated wake phase. Continue reading “Design of multi-particulate “Dome matrix” with sustained-release melatonin and delayed-release caffeine for jet lag treatment”

Keywords:  Caffeine, Delayed-release, Dome, Melatonin, Sustained-release, microcrystalline cellulose, extrusion, HPMC, hydroxyproplymethyl cellulose, Methocel,  alginate, chitosan,