Accuracy Study Of Tablets Split Dose And Impact On Children’s Medication Safety

Currently, pediatric formulations and specifications can not enough to meet the clinical needs, tablet splitting is a solution to resolve the contradiction. However, inaccurate dosage will be brought by tablet splitting, which caused pediatric potential problems, and affected pediatric therapeutic effect and safety.Objective:This study aimed to evaluate the temporary deployment of solid dosage forms and extemporaneously prepared liquid dosage forms, some frequently used tablets were utilized to evaluate the splitting accuracy, by examining the factors including weight, content and the stability, to find the current problems in tablet dosage redistribution, and propose the most appropriate method for different types of tablets, provide the reference to protect children from using ordinary tablets.Methods:Tablet splitting and milling sub-package were included for temporary redistribution for solid dosage forms. Eight kinds of tablets were selected, which were used most frequently. Four kinds of redistribution methods were evaluated including split by hand, split by scissors, split by blade and split by tablet-splitter, and the tablets were redistributed by bisection and quartered. After splitting, the unit weight was treated as indicator to evaluate the splitting accuracy by different ways.70mg of spironolactone tablet was used as a model drug for the evaluation of milling sub-package, Same tablet weight, different tablet weight, different operators, and operating at different times were considered to evaluate the redistribution effect. High-performance liquid chromatography was used to determined the drug content after redistributing and the microbial limit after redistributing was also examined.Spironolactone tablet and sildenafil citrate tablet was treated as a tool to evaluate the effects after extemporaneously prepared for liquid formulations. In order to investigate the stability, high performance liquid chromatography was used to determine the content changes of the both drug suspensions in different storage conditions, the microbial limits, appearance, and odor changes were also examined.Results:After tablet splitting,75%of the tablets split by tablet-splitter passed the1/2split test (the "European Pharmacopoeia"(version7.0),"Subdivision of tablets"); all tablets did not pass quartered split test. The split result of scored tablet was closest to the standard requirements, and tablet-splitter showed better split effect than the other three split methods. Split dose of the most methods of tablets splitting exceeded its target dose range from85%-115%.After redistributing by milling sub-package, all sub doses were failed to meet the "European Pharmacopoeia"(version7.0) of "Subdivision of tablets" With a larger proportion of the dose, the deviation of subcontracting was also increased; tablet weight showed obvious influence on the accuracy; redistributions by the same redistributor were relatively stable; and microbial limit could meet the "Chinese Pharmacopoeia" requirements.The main ingredient content did not change significantly (P>0.05, independent samples t-test) of the different suspension prepared in different drug delivery medium, different temperature and storage time under the different conditions. The physical and chemical stability were stable, and microbial limit could meet the "Chinese Pharmacopoeia" requirements.Conclusion:Tablet redistribution methods of solid dosage forms including tablets splitting and milling sub-package cannot fully guarantee the accuracy of the redistributed doses. Unless the tablets are scored which could lead to relatively accurate redistribution results, tablet redistribution methods including splitting and milling sub-package are not suggested to use frequently. Appropriate vehicle formulated to prepare drug suspension is suggested because of its stability in various environments are better, and the dose control is easy and accurate, so it is a good redistribution method to protect children’s basic safety and efficiency for clinical pediatric drug use.