Candelaria-Custodio, Madeline

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    Effect of initial formulation conditions, process parameters and equipment design on wet granulation
    (2020-07-24) Candelaria-Custodio, Madeline; Velázquez-Figueroa, Carlos; College of Engineering; Cardona Martínez, Nelson; Ortiz Bermúdez, Patricia; Córdova Figueroa, Ubaldo; Department of Chemical Engineering; Cruzado Vélez, Ivette
    Ease of administration and handling are some of the reasons to keep solid oral dosage forms as the presentation of predilection for today’s medicines. Today, pharmaceutical companies are looking for more efficient processes that could be fully understood and predicted based on initial formulation conditions and process parameters. In regards to this, wet granulation has been identified as one of the less understood and most unrepeatable processes during tablet manufacturing. But, currently most of the proposed models based on the Population Balance Equation (PBE) are empirical or semi-empirical, since not all factors are considered in the agglomeration kernels used and fundamental concepts are not always well understood to properly select the kernels that better describe the process. For these reasons, this dissertation aimed to provide a fundamental and practical understanding focused on the high shear wet granulation process on evaluating the effect on the final granule size of process parameters such as impeller speed and wet massing time, equipment design such as the impeller angle blade and initial formulation conditions such as the use of lubricated formulations. It also, combined the use of a statistical approach that revealed that all factors studied had some influence on the granule size obtained but also demonstrated that the factors studied did not completely explain the variability observed in the particle size distribution obtained by sieving tests, thus suggesting that there are some other uncontrolled factors not taken into consideration that are affecting the process. Since, most regulatory agencies and pharmaceutical industries are promoting the use of continuous processes due to its many advantages, this study also extended the same approach used in batch granulation to a continuous mixer that was modified to be used as a continuous granulator. The objective was to evaluate the effect of the granulator speed and the use of lubricated formulations on the size of the granules. In both cases, i.e. high shear wet granulation and continuous wet granulation, it was observed that lumps are controlled by the kinetic energy imparted to the particles during collisions and by the lubricant concentration which is directly related to the hydrophobicity of the formulation that impacts the binder distribution, confirming that the mechanisms behind the granule growth behavior does not change. In general, the proposed equipment was successfully used to conduct continuous wet granulation providing a simpler system than a continuous twin screw granulator which is the preferred system used in recent studies in this area.