Tuning the release of the pineal hormone melatonin via poly(ε-caprolactone)-based copolymers matrix tablets

Abstract

In our ongoing attempt to develop oral melatonin (MLT) oral solid dosage forms for the treatment of either sleep onset or sleep maintenance dysregulations, we have been experimented with a plethora of biopolymers with diverse structural features. In this study we present our findings on MLT's modified release in aqueous media, from polycaprolactone (PCL) and its copolymers, methoxy poly(ethylene glycol)-co-PCL (mPEG-PCL), glycerol-co-PCL (GLY-PCL), and pentaerythritol-co-PCL (PE-PCL), enriched with excipients, such as hydroxypropylmethylcellulose, sodium alginate, and lactose monohydrate. In most cases, when the PCL and PCL-based biopolymers were incorporated into the matrix tablets a controlled MLT's release pattern was achieved, and especially from the 1:1, mPEG-PCL, formulations. When the quantity of the PCL biopolymers is halved, melatonin is released substantially faster, due to the fact that these biopolymers exert their positive influence on the controlled release of the hormone, when present in higher quantities. The addition of HPMC K15 and sodium alginate in the formulations led, in general, to a delayed release. These results satisfy the targets sought about MLT's effect on fast sleep onset and/or sleep maintenance and constitute the basis for the design of in vivo experiments in the future.