Study On The Impacts Of Process Parameters Of Granulation & Tablet-compression On Tablet Quality

In order to meet the manufacturing process requirement of pharmaceutical industry in terms of high-level isolation, high-level automation and high-level continuum, get better understandings and control capability of the impact to product quality due to different parameters/variables, ensure the quality uniformity of different batches and improve quality management capability, the method of RSM (Response Surface Methodology) has been applied in this article to study the manufacturing process of tablet products, where the impact of 4 key parameters (binding agent, mix time, granules moisture and compression pressure) to the quality attributes of the granules and finished goods are analyzed and evaluated. The results turn out that all these 4 parameters will affect the tablets'quality attributes in different ways. The most significant impact to tablets hardness comes from the compression pressure, followed by the granules moisture and then the mixing time. Both compression pressure and binding agent significantly affect the tablets'disintegration time. Bigger compression pressure or more binding agent lead to prolonged disintegration time of the tablets. The mixing time and quantity of binding agent shows more impact on the weight of tablets than that of granules moisture. Based on the above facts, a data based model is established aiming to set up an optimized combination of these 4 key parameters that can be applied in the real production. In this experiment, based on the RSM study results, 3 groups of samples with similar parameters are adopted and 15 production batches are tested to validate the model.Based on the study of granules characteristics from 15 quality product batches, it is quite clear that the standard deviation of granule size distribution affect the weight RSD (relative standard deviation) of tablets quite significantly. The less granule size distribution standard deviation is, the less weight RSD and better uniformity will be. The study also indicates that the average granule diameter is a key factor that affects the hardness of tablets: Within certain range, the bigger the average granule diameter is, the harder the compressed tablets will be. Based on these analyses, a mathematical model and control limit of granules properties (granule size distribution standard deviation vs. tablet weight RSD, particle average diameter vs. tablet hardness) are proposed.The successful establishment of this model provides a scientific method for process optimization when technical transfer of the new products takes place. Effectively applying this model in process development and optimization will not only shortens the process validation cycles but also enable to secure stable quality attributes for mass production in the future.