口溶膜崩解时限评价方法对比研究

Comparative study on the methods to determine disintegration time of oral soluble films

崩解时限是影响口溶膜产品口感和用药顺应性的关键指标,目前尚无检测口溶膜崩解时限的标准方法。本研究对比考察药典崩解仪法、培养皿法、海绵法、小球法以及改进设计的不附重物式垂直液面崩解法和附重物式垂直液面崩解法这6种方法,测定4种不同厚度的西甲硅油口溶膜的体外崩解时限,并评价其与体内崩解时限的相关性。结果表明,药典崩解仪法和附重物式垂直液面崩解法的重复性和体内外相关性较好;附重物式垂直液面崩解法装置简单,崩解试验终点容易判断。附重物式垂直液面崩解法能够较好地模拟口腔内环境,该法可操作性强,分辨率、重复性及体内外相关性均良好,适用于进行口溶膜的体外崩解评价。本文成人感官味觉评价实验属于研究性质的临床试验,已按照药物临床试验质量管理规范的伦理要求,经所有受试者知情同意。

Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films.At present,there is no standard method to determine the disintegration time of oral soluble films.In this study,we compared the six methods(pharmacopoeial disintegration method,petri dish method,sponge surface method,slide frame and ball method,partially immersed into liquid(without weight attached)and partially immersed into liquid(with weight attached))to determine the in vitro disintegration time of oral soluble films with different thickness,and evaluated the correlation with the in vivo disintegration time.The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method(with weight attached)were excellent,with the endpoint of disintegration testing easy to determine.Partially immersed into liquid method(with weight attached),properly simulating the physiological condition in oral cavity,showed strong operability,good repeatability and in vitro-in vivo correlation,and was suitable for in vitro disintegration evaluation of oral soluble film dosage form.The adult sensory evaluation study was a researchbased clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.