RESUMO
The aim of this paper was to describe the influence of high-shear wet granulation process parameters on tablet tensile strength and compaction behavior of a powder mixture and granules containing hydralazine. The hydralazine powder mixture and eight types of granules were compacted into tablets and evaluated using the Heckel, Kawakita and Adams analyses. The granules were created using two types of granulation liquid (distilled water and aqueous solution of polyvinylpyrrolidone), at different impeller speeds (500 and 700 rpm) and with different wet massing times (without wet massing and for 2 min). Granulation resulted in improved compressibility, reduced dustiness and narrower particle-size distribution. A significant influence of wet massing time on parameters from the Kawakita and Adams analysis was found. Wet massing time had an equally significant effect on tablet tensile strength, regardless of the granulation liquid used. Granules formed with the same wet massing time showed the same trends in tabletability graphs. Tablets created using a single-tablet press (batch compaction) and an eccentric tablet press showed opposite values of tensile strength. Tablets from granules with a higher bulk density showed lower strength during batch compaction and, conversely, higher strength during eccentric tableting.
RESUMO
The aim of the work was to analyze the influence of process parameters of high shear granulation on the process yield and on the morphology of granules on the basis of dynamic image analysis. The amount of added granulation liquid had a significant effect on all monitored granulometric parameters and caused significant changes in the yield of the process. In regard of the shape, the most spherical granules with the smoothest surface were formed at a liquid to solid ratio of ≈1. The smallest granules were formed at an impeller speed of 700 rpm, but the granules formed at 500 rpm showed both the most desirable shape and the highest process yield. Variation in the shape factors relied not only on the process parameters, but also on the area equivalent diameter of the individual granules in the batch. A linear relationship was found between the amount of granulation liquid and the compressibility of the granules. Using response surface methodology, models for predicting the size of granules and process yield related to the amount of added liquid and the impeller speed were generated, on the basis of which the size of granules and yield can be determined with great accuracy.
RESUMO
The aim of this systematic study was to analyze the granulometric and rheological behavior of tableting mixtures in relation to tabletability by single tablet and lab-scale batch compression with an eccentric tablet machine. Three mixtures containing 33, 50, and 66% of the cohesive drug paracetamol were prepared. The high compressibility of the powder mixtures caused problems with overcompaction or lamination in the single tablet compression method; due to jamming of the material during the filling of the die, the lab-scale batch compression was impossible. Using high shear granulation, the flow properties and tabletability were adjusted. A linear relationship between the span of granules and the specific energy measured by FT4 powder rheometer was detected. In parallel, a linear relationship between conditioned bulk density and the tensile strength of the tablets at lab-scale batch tableting was noted. The combination of dynamic image analysis and powder rheometry was useful for predicting the tabletability of pharmaceutical mixtures during the single tablet (design) compression and the lab-scale batch compression.
