PARO Newsletter #8 | English version
This equipment works with small amounts of raw material (15 to 20 grams), which are allocated in a mixing compartment. Two rotating blades, coupled to a signal transducer, will homogenize the sample. So that it will be possible to obtain a torque value, measured and calculated by the CalevaMTR ® software, through one of three different analytical methods: Consistency (used to check properties of powders produced in large-scale granulation systems and can be used as a quality control tool), Variable Mixed Time (provides an indication of the torque response in relation to the binder ratio and mixing time) and Multiple Addition (used to study the best granulation condition and determine its endpoint). In addition, the Feb. de 2020 | Vol. 8
Multiple Addition method, in combination with statistical planning for the formulation of pharmaceutical granulates, allows the optimization of the multiparticulate formulations development, making it possible to choose the best proportions of active pharmaceutical ingredient (API) and excipients for the composition of the formulation. Thus, the formulator acquires full knowledge of the formulation and its processing parameters, guaranteeing the quality of the product from the first stages of development, as provided by Quality by Design (QbD) (MISHRA; ROHERA, 2016). Figure 2. Intensity curve of the average torque as a function of the liquid / solid ratio.
As a practical example, there is caffeine, an API that has poor flow, poor compressibility index and can be used in high doses as an energy supplement. In this context, the production of caffeine-containing tablets is conditioned to its granulation. In order to choose the best formulation containing caffeine and determine its endpoint, a 3 3-1 fractional factorial design, resulting in 9 formulations, was planned and evaluated on the MTR under the following conditions: 60-second mix time, blade rotation at 50 rpm and log time of 20 seconds. After evaluating the results of the 9 formulations, the one with the highest maximum torque value was chosen, consisting of 30% caffeine, 1% carrageenan and Avicel ® 101 in sufficient quantity to complete 15 grams of sample. Then, through the rheological profile of this formulation (Figure 3), it was possible to determine the granulation endpoint of. It is important to emphasize that, as presented by Belem and Ferraz (2020), the ideal final stage still a contradictory topic among several authors. Some defend the choice of a point between the pendular and funicular stages, others defend a point between the funicular and capillary and, finally, there are those who follow the line that the capillary stage can be considered a good approximation of the granulation endpoint. In the present study, we opted to follow this last research line, so that the capillary stage (maximum torque) was adopted as the granulation endpoint. According to Figure 3, the liquid / solid ratio required to achieve the highest torque value is 0.8 mL / g. So to produce 200 grams of this granulate, is necessary to add 160 mL of the binder liquid to the solid mixture, thus defining the granulation endpoint.
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