Modified Release of the Pineal Hormone Melatonin from Matrix Tablets Containing Poly(L-lactic Acid) and Its PLA- co-PEAd and PLA- co-PBAd Copolymers

Marilena Vlachou; Angeliki Siamidi; Dionysia Anagnostopoulou; Evi Christodoulou; Nikolaos D Bikiaris

doi:10.3390/polym14081504

Modified Release of the Pineal Hormone Melatonin from Matrix Tablets Containing Poly(L-lactic Acid) and Its PLA- co-PEAd and PLA- co-PBAd Copolymers

Polymers (Basel). 2022 Apr 7;14(8):1504. doi: 10.3390/polym14081504.

Authors

Marilena Vlachou¹, Angeliki Siamidi¹, Dionysia Anagnostopoulou¹, Evi Christodoulou², Nikolaos D Bikiaris²

Affiliations

¹ Division of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 15784 Athens, Greece.
² Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Abstract

In terms of drug delivery, the attractive properties of poly(L-lactic acid) (PLA) and its aliphatic polyesters, poly(ethylene adipate) (PEAd) and poly(butylene adipate) (PBAd), render them ideal co-formulants for the preparation of modified-release pharmaceutical formulations. Furthermore, we have previously demonstrated that by adding a "softer" aliphatic polyester onto the macromolecular chain of PLA, i.e., PEAd or PBAd, resulting in the formation of the PLA's copolymers (PLA-co-PEAd and PLA-co-PBAd, in 95/5, 90/10, 75/25 and 50/50 weight ratios), the hydrolysis rate is also severely affected, leading to improved dissolution rates of the active pharmaceutical ingredients (API). In the present report, we communicate our findings on the in vitro modified release of the chronobiotic hormone melatonin (MLT), in aqueous media (pH 1.2 and 6.8), from poly(L-lactic acid) and the aforementioned copolymer matrix tablets, enriched with commonly used biopolymers, such as hydroxypropylmethylcellulose (HPMC K15), lactose monohydrate, and sodium alginate. It was found that, depending on the composition and the relevant content of these excipients in the matrix tablets, the release of MLT satisfied the sought targets for fast sleep onset and sleep maintenance. These findings constitute a useful background for pursuing relevant in vivo studies on melatonin in the future.

Keywords: PLA-co-PEAd and PLA-co-PBAd copolymers; dissolution; melatonin; modified-release matrix tablets; poly(L-lactic acid) (PLA).