Estudo da influência de diferentes adjuvantes na partição de comprimidos

• Autor(a) principal: Pereira, Gessyka Rayana Silva
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/9689
• topic: Partição de comprimidos; Diluentes; Aglutinantes; Planejamento de mistura; Tablet splitting; Diluents; Binders; Mixing planning; CIENCIAS DA SAUDE::FARMACIA

Introduction: Tablet splitting is an extensively performed practice mainly for the purpose of dose adjustment. This practice is associated with significant health risks due to administration of doses that are different from those clinically recommended. Few studies have investigated the influence of the qualitative and quantitative composition of adjuvants on the quality of the tablet splitting. Objective: The objective of this study was to evaluate the accuracy of the tablet splitting produced by wet granulation and containing different diluents (microcrystalline cellulose - MCC and calcium phosphate dibasic dihydrate - CPD) and binders (hydroxypropyl cellulose - HPC and povidone K-30 - PVP), using a combined mix design, in order to suggest an optimum formulation that allows to achieve satisfactory post-splitting results. Methodology: The granules were obtained by wet granulation using hydroethanolic solution as a binder liquid. The materials were dried in an air circulating oven and then had their average particle size, size distribution, apparent density and tapped density, Carr index and Hausner factor determined. Next, the tablets were obtained on a rotary machine using an 11.5 mm diameter unscored round punch set. Different compaction forces were used to keep tablet hardness and thickness at the same level for all formulations. Tablet splitting was performed using a commercial tablet splitter and the results of loss and variation of mass and friability were statistically analyzed. Results and discussion: The average hardness and thickness of the tablets were 64N (± 2N) and 4.46mm (± 0.03mm), respectively. The friability of all formulations was less than 1.5%, in accordance with the specifications of the Brazilian Pharmacopoeia. Splitting tests showed that the use of MCC as a diluent led to loss and mass variation of 2.85% and 11.03%,respectively. On the other hand, formulations containing only CPD as diluent showed 1.82% and 8.18% of loss and mass variation, respectively. The type of diluent had a significant effect on these responses according to the mix design used. The type of binder significantly affected the mass loss and mass variation only in the MCC tablets, which were negatively influenced by the presence of PVP. The lowest friability variation was observed in the tablets containing CPD and the mixture of HPC and PVP (0.47%). This composition (100% CPD and PVP-HPC mixture, 1:1) was defined as optimum for splitting according to the desirability analysis. Cross-sectional photomicrographs of the different tablets suggested that the presence of cellulose fibers reduced matrix uniformity, and this may be related to the greater variations observed in the splitted halves. Conclusions: Placebo tablets obtained by wet granulation presented better splittability and generated less friable halves when prepared CPD. The filler mixture and the interaction between diluent and binder affected tablet splitting. The desirability function allowed to suggest the filler : binder ratios with higher potential to produce tablets with good splitabillity.