【摘要】：目前,兒科用藥可供選擇的劑型和規(guī)格不足,不能滿足臨床需要,片劑的分劑量是臨床上解決這一用藥矛盾的常用方法。但,片劑分劑量帶來的劑量不準確是兒科用藥潛在的問題,影響了兒科用藥的治療效果和安全性。 目的：本研究擬通過臨時調(diào)配的固體劑型以及臨時調(diào)配液體劑型兩個方面,對部分分劑量頻次高的藥片進行分劑量準確性研究,通過考察分劑量后藥品重量、含量以及穩(wěn)定性等因素,發(fā)現(xiàn)目前兒科用藥片劑分劑量中存在的問題,并為不同類型的片劑給出最適宜的分劑量方法,為保障兒童使用普通片劑的用藥安全提供客觀依據(jù)。 方法：臨時調(diào)配的固體劑型部分,包括藥片分劈和磨粉分包兩種方式。藥片分劈選用病區(qū)藥房8種常需分劈的藥片,用手工、剪刀、刀片和切藥器四種分劈方法對實驗藥片進行二等分和四等分,以分劈后重量為指標對不同分劈方式的分劑量準確性進行評價。磨粉分包以片重為70mg的螺內(nèi)酯片為模型藥,‘考察相同片重、不同片重、不同操作人員以及相同操作人員不同時間的分包效果,用高效液相色譜法對分包后的含量進行測定,并考察分包后的微生物限度。 臨時調(diào)配的液體劑型部分,以螺內(nèi)酯片和枸櫞酸西地那非片為工具藥,使用高效液相色譜法測定兩種藥物混懸液在不同存儲條件下的含量變化,并考察微生物限度以及外觀性狀和氣味的變化,以考察其穩(wěn)定性。 結(jié)果：藥片分劈后,75%的藥片通過了切藥器1/2片分劈測試(7.0版《歐洲藥典》的藥片分劑量準確性測試)；所有分劈方式均未通過1/4片分劈測試。帶有分劈刻痕的藥片分劈結(jié)果最接近標準要求,切藥器的分劈效果優(yōu)于其他三種分劈方法。多數(shù)方法分劈藥片所得的劑量超出了其目標劑量的85%～115%范圍。 藥片磨粉分包后,所有分包均未能達到《歐洲藥典》(7.0版)的藥片分劑量準確性測試方法的標準。隨分劑量比例增大,分包結(jié)果的偏差增大；藥片重量對分劑量的準確性影響較大；相同分包人員的分包結(jié)果相對穩(wěn)定；分包后微生物限度檢查符合《中國藥典》規(guī)定。 研究中配制的不同混懸液,在不同遞藥介質(zhì)、不同溫度、不同存放時間條件下主要成分含量未發(fā)生明顯變化(P0.05,獨立樣本t檢驗),能夠保持物理和化學(xué)的穩(wěn)定性,微生物限度符合《中國藥典》規(guī)定。 結(jié)論：固體形式的片劑分劑量方式,包括藥片分劈、磨粉分包都不能完全保證片劑分劑量的準確性。當(dāng)片劑留有分劈刻痕的條件下,藥片分劈的劑量相對較為準確和穩(wěn)定,除此以外的藥片分劈和磨粉分包形式在有其他選擇方案時要盡量減少使用。而使用適宜遞藥介質(zhì)配制的藥物混懸液在各種環(huán)境下的穩(wěn)定性均較好,劑量容易準確控制,是臨床上兒童用藥的良好分劑量方式,基本能夠保障兒童用藥的安全性和有效性。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R95

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