Avaliação técnica aplicada ao circuito de granulação em indústria de comprimidos farmacêuticos

Abstract

The production of pharmaceutical tablets by wet granulation method involves the preparation of granulating solution, granulation, fluidized bed drying and calibration. During the drying of the product Atenolol, there is a known history of dry granulated powder loss in the fluidized dryer both in the region below the bed bowl and by entrainment of fine particles through the baghouse. As part of the actions implemented by the Manufacturing, Science and Technology sector, the reincorporation of the plenum material was adopted and the baghouse was replaced. Thus, the present work studied the functioning, importance and influence of the unit operations of wet granulation and fluidized bed drying in the production of pharmaceutical tablets, using qualitative and quantitative methods to investigate the losses. In the qualitative scope, an interview was conducted with the Maintenance and the Manufacturing, Science and Technology sectors in order to clarify the critical points of the circuit and associated operations; the Ishikawa method was applied to identify the possible causes related to the problem and the mesh of the dryer bag filter was analyzed. Regarding the quantitative approach, the dry granulate was characterized using sieving, dynamic light scattering and scanning electron microscopy methods. The losses were quantified by applying mass balance and their economic impact based on the price of the medicine for the consumer was calculated. The inspection of the filter in operation confirmed its structural integrity at the points evaluated. The micrograph of the dry material elucidated the topography of the granulate produced and its compliance with theoretical expectations. The characterization of the particles showed average size distribution between 74 μm and 38 μm for the bed and between 149 μm and 74 μm for the powder directed to the equipment plenum. The material balance and the economic impact calculated allowed the quantification and evaluation of the effective process losses, which occurred mainly due to the rejection of dust to the air treatment system downstream and adhesion to the equipment walls. Batches with a higher fraction of fines resulted in a greater need for recycling and reincorporation was identified as of utmost importance for maintaining high circuit performance. In conclusion, it was recommended to continue the reincorporation process and to explore the supply of magnesium carbonate from alternative manufacturers.