Vlachou Marilena, Siamidi Angeliki, Anagnostopoulou Dionysia, Christodoulou Evi, Bikiaris Nikolaos D
Division of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 15784 Athens, Greece.
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Polymers (Basel). 2022 Apr 7;14(8):1504. doi: 10.3390/polym14081504.
In terms of drug delivery, the attractive properties of poly(-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--PEAd and PLA--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(-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.
在药物递送方面，聚（-乳酸）（PLA）及其脂肪族聚酯聚（己二酸乙二酯）（PEAd）和聚（己二酸丁二酯）（PBAd）具有吸引人的特性，使其成为制备缓释药物制剂的理想共配方辅料。此外，我们之前已经证明，通过在PLA的大分子链上添加一种“较软”的脂肪族聚酯，即PEAd或PBAd，从而形成PLA的共聚物（PLA-PEAd和PLA-PBAd，重量比为95/5、90/10、75/25和50/50），水解速率也会受到严重影响，进而提高活性药物成分（API）的溶解速率。在本报告中，我们阐述了关于在水性介质（pH 1.2和6.8）中，从聚（-乳酸）和上述共聚物基质片剂中体外缓释生物钟激素褪黑素（MLT）的研究结果，这些片剂富含常用的生物聚合物，如羟丙基甲基纤维素（HPMC K15）、一水乳糖和海藻酸钠。结果发现，根据基质片剂中这些辅料的组成和相关含量，MLT的释放满足了快速入睡和维持睡眠的预期目标。这些发现为未来开展关于褪黑素的相关体内研究提供了有用的背景资料。
