BACKGROUND:In many countries, hypertension in the pediatric population is considered a serious risk of mortality and morbidity. In this respect, it is central to design and develop new pharmaceutical forms for pediatric patients with hypertension. The development of Orodispersible Mini-Tablets (ODMTs) for pediatric use has gained importance in recent years. Therefore, regulations for developing suitable and palatable dosage forms for pediatric patients have been established by WHO authorities. OBJECTIVE:This study aimed to design and develop orodispersible mini tablets of enalapril maleate (EnM ODMTs) for pediatric use. METHODS:Five pharmaceutical formulations (A, B, C, D and E, shown in Table 1) were designed. The effects of different co-processed excipients and active pharmaceutical ingredients at different doses were studied. Lactose co-processed excipients selected were the following: Tablettose® 80, Microce- Lac® 100 and StarLac®. The micromeritic properties for all the physical mixtures were examined. The mini tablets were obtained by direct compression. Quality control parameters were determined in accordance with US Pharmacopeia. RESULTS:Three OMDTs with StarLac® showed good results of hardness, flow ability and fast disintegration. The formulation with 0.1 mg of enalapril maleate presented the best results for the official parameters of hardness (4.0 kp), friability (< 1%), disintegration time (28 s), drug content uniformity (103.6 %), and wetting time (23 s). CONCLUSION:The three OMDTs with StarLac® showed good quality parameters, according to official requirements. Formulation A exhibited the best wetting time, complying with the dose recommended for pediatric patients. This formulation could be considered eligible for being manufactured at industrial scale.

译文

背景:在许多国家,小儿人群的高血压被认为具有严重的死亡和发病风险。在这方面,为小儿高血压患者设计和开发新的药物形式是至关重要的。近年来,用于儿童的可口分散小片剂(ODMT)的开发变得越来越重要。因此,世卫组织当局已经制定了开发适用于儿科患者的合适且可口的剂型的法规。
目的:本研究旨在设计和开发用于儿科的马来酸依那普利口服分散微型片剂(EnM ODMTs)。
方法:设计了五种药物制剂(表1所示为A,B,C,D和E)。研究了不同剂量的不同共处理的赋形剂和活性药物成分的作用。选择的乳糖共加工的赋形剂如下:Tablettose®80,Microce-Lac®100和StarLac®。检查了所有物理混合物的微链性能。通过直接压制获得小片剂。根据美国药典确定质量控制参数。
结果:三种采用StarLac®的OMDT显示出良好的硬度,流动性和快速崩解效果。含有0.1 mg马来酸依那普利的配方在以下各项的官方参数中表现出最好的结果:硬度(4.0 kp),脆碎度(<1%),崩解时间(28 s),药物含量均匀性(103.6%)和润湿时间(23) s)。
结论:根据官方要求,采用StarLac®的三种OMDT显示出良好的质量参数。配方A表现出最佳的润湿时间,符合儿科患者推荐的剂量。可以认为该制剂符合工业规模生产的条件。

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