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Development of spray-dried melatonin loaded chitosan microparticles using factorial design

Melatonin, methoxyindole secreted by the pineal gland, has pleiotropic bioactivities as a neurotransmitter, hormone, cytokine and biological-response modifier. Melatonin regulates circadian and seasonal biorhythms, modulates immune defense responses, body weight and reproduction, and displays tumor growth inhibitory and anti-jet-lag effects. Moreover, melatonin is potent antioxidant, chemotoxicity reducing agent and anti-aging substance. Administration of exogenous melatonin has been investigated with respect to a wide range of pathologies. Oral melatonin tablets show poor absolute bioavailability, due to poor oral absorption and large first-pass metabolism. To solve this problem, novel therapeutic systems for other rutes of administration need to be developed. Spray-drying is recognised as a suitable method for the preparation of dry particles with desired properties. Chitosan microparticles allow contolled release, better bioaviability and improved drug delivery across epithelial barriers. The aim of this study was to investigate the effect of process and formulation parameters on the properties of microparticles prepared by spray-drying method, using a 25-1 fractional factorial design. Melatonin loaded chitosan and P407/chitosan microparticles were characterised by production yield, particle size, surface charge and moisture content. Results from these studies suggest the significant influence of several process and formulation parameters and their interactions on the investigated microparticle properties. Inlet temperature had the greatest influence on production yield (higher temperature giving loer yields), P407 had the greatest influence on particle size (presence of P407 giving larger particles), chitosan concentration mostly influenced surface charge (higher chitosan concentration giving higher particle surface charge), melatonin/chitosan weight ratio had the greatest influence on moisture content (higher melatonin ratio giving lover moisture content). Chitosan concentration of 8 g/L, P407 concentration of 1, 6 g/L, melatonin to chitosan weight ratio of 1:2, inlet temperature of 145 °C and pump rate of 2, 59 mL/min are chosen as optimal formulation and process parameters for the production of melatonin loaded chitosan microparticles by spray-drying. According to above parametar values, additional batches were prepared and characterised. The results show that spray-drying is a suitable technique for the preparation of melatonin loaded chitosan microparticles with desirable properties.

factorial design; melatonin; chitosan; poloxamer 407 (P407); spray-drying

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