Key Technical Aspects Influencing the Accuracy of Tablet Subdivision

Abstract

Tablet subdivision is a common practice used mainly for dose adjustment. The aim of this study was to investigate how the technical aspects of production as well as the method of tablets subdivision (employing a tablet splitter or a kitchen knife) influence the accuracy of this practice. Five drugs commonly used as subdivided tablets were selected. For each drug, the innovator drug product, a scored-generic and a non-scored generic were investigated totalizing fifteen drug products. Mechanical and physical tests, including image analysis, were performed. Additionally, comparisons were made between tablet subdivision method, score, shape, diluent composition and coating. Image analysis based on surface area was a useful tool as an alternative assay to evaluate the accuracy of tablet subdivision. The tablet splitter demonstrates an advantage relative to a knife as it showed better results in weight loss and friability tests. Oblong, coated and scored tablets had better results after subdivision than round, uncoated and non-scored tablets. The presence of elastic diluents such as starch and dibasic phosphate dehydrate conferred a more appropriate behaviour for the subdivision process than plastic materials such as microcrystalline cellulose and lactose. Finally, differences were observed between generics and their innovator products in all selected drugs with regard the quality control assays in divided tablet, which highlights the necessity of health regulations to consider subdivision performance at least in marketing authorization of generic products.

Partição de Comprimidos Antineoplásicos Utilizados no Tratamento de Leucemias Agudas em Crianças e Adolescentes

“…Em relação à percepção de alterações nos comprimidos antineoplásicos partidos, os resultados demonstraram que 16 entrevistados (33,33%) relataram esfarelamento dos comprimidos, o que é potencialmente prejudicial ao ambiente doméstico 29 . O esfarelamento interfere na variação de peso do comprimido que, segundo Teixeira et al 30 , é um dos índices mais importantes para definir a segurança de um processo de subdivisão porque é relacionado diretamente à dose quando a substância ativa está uniformemente distribuída na massa do comprimido 30 . Neste estudo, é ainda mais relevante por serem quimioterápicos citotóxicos 11,12,17,27,28 , que podem ocasionar contaminação e risco à saúde para os responsáveis pela partição 25 , bem como para quem utiliza os medicamentos.…”

“…Além disso, o partidor, por apresentar uma lâmina afiada, necessita de maior atenção e cuidado ao ser manipulado 25 . Estudo experimental comparando a utilização de partidor de comprimidos e faca demonstrou que a variação de peso dos comprimidos partidos é menor entre os fragmentos obtidos por partidor, comparados àqueles obtidos com uma faca 30 . O estudo experimental de Habib et al 31 avaliou a precisão da divisão comparando a utilização de partidor de comprimidos versus das mãos para partir comprimidos de salbutamol 4 mg e demonstrou que o uso de um partidor é mais preciso e superior à divisão manual, pois leva a uma menor variação de peso e de teor do fármaco entre as partes.…”

Tablet Scoring: Current Practice, Fundamentals, and Knowledge Gaps

“…In a study that was conducted using placebo tablets manufactured using MCC and DCP, it was noted that MCC produced less uniform and less dense tablets compared to those produced with DCP [149]. Tablets manufactured with elastic diluents such as starch and DCP are more amenable to partitioning that those manufactured with plastic materials such as microcrystalline cellulose and lactose [168]. Crystalline lactose is considered a brittle material because of its susceptibility to fracture when stress is exerted [169,170].…”

“…(b) Non-conventional shaped tablets. Certain tablet shapes may be difficult to partition, since the geometry of the tablet plays a crucial role in positioning the embossing scored line in the tablet [168]. (c) Fragments or crumble tablets.…”

Recent trends in tablet subdivision and factors affecting subdivision in South Korea

“…However, not all tablets are suitable for subdivision. [ 1 , 2 , 10 – 12 ] Subdivision of extended release formulations might induce unintended consequences regarding the safety of patients. [ 12 – 14 ] For instance, subdivision could result in toxicity from uncontrolled release of an active ingredient and sometimes active ingredients in enteric-coated formulations are destroyed when subdivided.…”