Filali Samira, Bergamelli Charlotte, Lamine Tall Mamadou, Salmon Damien, Laleye Diane, Dhelens Carole, Diouf Elhadji, Pivot Christine, Pirot Fabrice
Service pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, 5 Place d'Arsonval, F-69437 Lyon Cedex 03, France.
Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle, Plateforme FRIPHARM, Faculté de Pharmacie, Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique - UMR 5305, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon Cedex 08, France.
J Pharm Anal. 2017 Aug;7(4):237-243. doi: 10.1016/j.jpha.2017.04.001. Epub 2017 Apr 6.
A new institutional clinical trial assessed the improvement of sleep disorders in 40 children with autism treated by immediate-release melatonin formulation in different regimens (0.5 mg, 2 mg, and 6 mg daily) for one month. The objectives of present study were to (i) prepare low-dose melatonin hard capsules for pediatric use controlled by two complementary methods and (ii) carry out a stability study in order to determine a use-by-date. Validation of preparation process was claimed as ascertained by mass uniformity of hard capsules. Multicomponent analysis by attenuated total reflectance Fourier transformed infrared (ATR-FTIR) of melatonin/microcrystalline cellulose mixture allowed to identify and quantify relative content of active pharmaceutical ingredients and excipients. Absolute melatonin content analysis by high performance liquid chromatography in 0.5 mg and 6 mg melatonin capsules was 93.6%±4.1% and 98.7%±6.9% of theoretical value, respectively. Forced degradation study showed a good separation of melatonin and its degradation products. The capability of the method was 15, confirming a risk of false negative <0.01%. Stability test and dissolution test were compliant over 18 months of storage with European Pharmacopoeia. Preparation of melatonin hard capsules was completed manually and melatonin in hard capsules was stable for 18 months, in spite of low doses of active ingredient. ATR-FTIR offers a real alternative to HPLC for quality control of high-dose melatonin hard capsules before the release of clinical batches.
一项新的机构临床试验评估了40名自闭症儿童使用速释褪黑素制剂以不同方案（每日0.5毫克、2毫克和6毫克）治疗一个月后睡眠障碍的改善情况。本研究的目的是：（i）通过两种互补方法制备儿科用低剂量褪黑素硬胶囊，以及（ii）进行稳定性研究以确定有效期。硬胶囊的质量均匀性确定了制备过程的验证。通过衰减全反射傅里叶变换红外光谱（ATR-FTIR）对褪黑素/微晶纤维素混合物进行多组分分析，可识别和量化活性药物成分和辅料的相对含量。0.5毫克和6毫克褪黑素胶囊中通过高效液相色谱法进行的褪黑素绝对含量分析分别为理论值的93.6%±4.1%和98.7%±6.9%。强制降解研究表明褪黑素与其降解产物有良好的分离。该方法的能力为15，确认假阴性风险<0.01%。稳定性试验和溶出度试验在储存18个月期间符合欧洲药典标准。褪黑素硬胶囊的制备是手工完成的，尽管活性成分剂量较低，但硬胶囊中的褪黑素在18个月内保持稳定。在临床批次发布之前，ATR-FTIR为高剂量褪黑素硬胶囊的质量控制提供了一种切实可行的替代HPLC的方法。
