Nasal melatonin gels using pluronic PF-127 for chronobiological treatment of sleep disorder

Abstract

Melatonin, a neurohormone, is formulated as a thermoreversible pluronic gel for nasal administration as an ‘overlap dosage form’ for chronobiological treatment of sleep disorders. Aqueous PF gels containing drug (0.5 mg & 1 mg/0.1 ml), PEG 400 and PEG 15,000 were prepared by cold method. Pluronic gels were evaluated for gelation and gel melting. Gelation temperature (T₁) decreased with pluronic concentration while gel melting temperature (T₂) increased. Melatonin shifted gelation range to higher temperature while PEG narrowed the gel range. Flux of diffusion decreased with PF concentration. Drug flux decreased in higher drug strength gels due to more partitioning in micellar phase. Pluronic gel (20%w/w, 1 mg/0.1 ml) showed bimodal pattern with a desired second peak flux (0.248<img src='/image/spc_char/micro.gif'>g/min/cm²) at 300 min. Flux pattern changed invariably with PEG. Bioadhesion time and strength to sheep nasal mucosa were more for gels containing melatonin and PEG 400. Nasal gels produced fast onset of action and induced sleep within fifteen minutes. The low intensity and rounded <img src='/image/spc_char/alpha.gif'>-EEG wave pattern was observed for sleep duration of 5 hrs. Good correlation was observed in sleep pattern and low intensity <img src='/image/spc_char/alpha.gif'>-EEG. The results are encouraging and nasal melatonin gels have potential in the treatment of circadian cycle sleep disorders.