药片分剂量准确性考察及对儿童用药安全的影响

发布时间：2018-11-10 14:18

【摘要】：目前,儿科用药可供选择的剂型和规格不足,不能满足临床需要,片剂的分剂量是临床上解决这一用药矛盾的常用方法。但,片剂分剂量带来的剂量不准确是儿科用药潜在的问题,影响了儿科用药的治疗效果和安全性。目的：本研究拟通过临时调配的固体剂型以及临时调配液体剂型两个方面,对部分分剂量频次高的药片进行分剂量准确性研究,通过考察分剂量后药品重量、含量以及稳定性等因素,发现目前儿科用药片剂分剂量中存在的问题,并为不同类型的片剂给出最适宜的分剂量方法,为保障儿童使用普通片剂的用药安全提供客观依据。方法：临时调配的固体剂型部分,包括药片分劈和磨粉分包两种方式。药片分劈选用病区药房8种常需分劈的药片,用手工、剪刀、刀片和切药器四种分劈方法对实验药片进行二等分和四等分,以分劈后重量为指标对不同分劈方式的分剂量准确性进行评价。磨粉分包以片重为70mg的螺内酯片为模型药,‘考察相同片重、不同片重、不同操作人员以及相同操作人员不同时间的分包效果,用高效液相色谱法对分包后的含量进行测定,并考察分包后的微生物限度。临时调配的液体剂型部分,以螺内酯片和枸橼酸西地那非片为工具药,使用高效液相色谱法测定两种药物混悬液在不同存储条件下的含量变化,并考察微生物限度以及外观性状和气味的变化,以考察其稳定性。结果：药片分劈后,75%的药片通过了切药器1/2片分劈测试(7.0版《欧洲药典》的药片分剂量准确性测试)；所有分劈方式均未通过1/4片分劈测试。带有分劈刻痕的药片分劈结果最接近标准要求,切药器的分劈效果优于其他三种分劈方法。多数方法分劈药片所得的剂量超出了其目标剂量的85%～115%范围。药片磨粉分包后,所有分包均未能达到《欧洲药典》(7.0版)的药片分剂量准确性测试方法的标准。随分剂量比例增大,分包结果的偏差增大；药片重量对分剂量的准确性影响较大；相同分包人员的分包结果相对稳定；分包后微生物限度检查符合《中国药典》规定。研究中配制的不同混悬液,在不同递药介质、不同温度、不同存放时间条件下主要成分含量未发生明显变化(P0.05,独立样本t检验),能够保持物理和化学的稳定性,微生物限度符合《中国药典》规定。结论：固体形式的片剂分剂量方式,包括药片分劈、磨粉分包都不能完全保证片剂分剂量的准确性。当片剂留有分劈刻痕的条件下,药片分劈的剂量相对较为准确和稳定,除此以外的药片分劈和磨粉分包形式在有其他选择方案时要尽量减少使用。而使用适宜递药介质配制的药物混悬液在各种环境下的稳定性均较好,剂量容易准确控制,是临床上儿童用药的良好分剂量方式,基本能够保障儿童用药的安全性和有效性。
[Abstract]:At present, the dosage forms and specifications of pediatric drugs are insufficient and can not meet the clinical needs. However, the inaccuracy of the dosages of tablets is a potential problem of pediatric drugs, which affects the efficacy and safety of paediatric drugs. Objective: the purpose of this study was to study the accuracy of partial dose-sharing tablets with high frequency through two aspects: the temporary preparation of solid preparations and the temporary formulation of liquid formulations, and the weight of the drugs after partial dosages were investigated. The content and stability of paediatric tablets were found out, and the most suitable dose-dividing methods for different kinds of tablets were given, which provided the objective basis for the safety of children using common tablets. Methods: temporary preparation of solid formulations, including split tablets and grinding powder subcontract two ways. The tablets were divided into eight kinds of tablets which were often required to be split in the pharmacy of the disease area. The experimental tablets were divided into two and four equal groups by hand, scissors, blades and drug cutters. The dosimetric accuracy of different splitting methods was evaluated with the weight after splitting. The grinding powder was subcontracted with spironolactone tablets with 70mg weight as the model drug. The effects of subcontracting with the same weight, different operators and the same operators at different time were investigated, and the content of the subcontract was determined by HPLC, the content of which was determined by high performance liquid chromatography (HPLC). The microbial limit after subcontracting was investigated. In the liquid form of temporary preparation, spironolactone tablets and sildenafil citrate tablets were used as tools to determine the content changes of the suspension of the two drugs under different storage conditions by HPLC. The microbial limit and the changes of appearance characters and odors were investigated to investigate its stability. Results: after splitting, 75% of the tablets passed the 1 / 2 split test (7.0 version of European Pharmacopoeia), and none of them passed the 1 / 4 split test. The result of tablet splitting with split mark is most close to the standard requirement, and the effect of the cutting device is better than the other three methods. In most cases, the dose of the split pill exceeds its target dose by 85% to 115%. After the grinding powder was subcontracted, all the subcontracts failed to meet the standard of the test method of minute dose accuracy of tablets in the European Pharmacopoeia (version 7.0). With the increase of sub-dose ratio, the deviation of subcontract results increased; the weight of tablets had a great influence on the accuracy of sub-dosages; the subcontract results of the same subcontractors were relatively stable; the microbial limit examination of the same subcontractors was in accordance with the provisions of the Chinese Pharmacopoeia. Different suspensions were prepared in different delivery medium, different temperature, different storage time, the main components content did not change significantly (P0.05, independent sample t-test), can maintain the physical and chemical stability, The microbial limit is in accordance with the Chinese Pharmacopoeia. Conclusion: the accuracy of tablets can not be completely guaranteed by the solid form of tablets, including tablet splitting and grinding powder subcontract. The dosage of tablet splitting is relatively accurate and stable when the tablet has split marks. In addition, the tablet splitting and grinding subcontract forms should be minimized when other options are available. The drug suspension prepared with suitable drug delivery medium has good stability in various environments, and the dosage is easy to be accurately controlled. It is a good dose-sharing method for children in clinical use, and can basically ensure the safety and effectiveness of drug use in children.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R95

【参考文献】