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Tablets & Capsules January 2017 35 Thus, in a pre-mixing phase that calls for different impeller speeds, different rates and patterns of splattering will occur and the makeup of the powders adhering to the vessel's interior will vary. If the powder isn't scraped off and returned to the powder bed before wet massing begins, some of the increasingly wetted powder will adhere to the vessel's interior and/or the splattered dry powder. Over time, the splattered powders may or may not fall back into the in-motion powder bed, and how much powder returns and at what point during the wet massing phase will affect the degree of variation in the outcome. This is true regardless of whether the spray rate, impeller speed, and/or probe-based endpoint deter- mination were under tight control. That's why it's better to periodically scrape the pow- der from the vessel walls: If done at the same intervals in the process, it standardizes the outcome. Naturally, you must cite the frequency of scraping as a critical operating parameter in your batch records. The photos above show the variability of how different APIs/formulations per- form during wet granulation. Each could require different scraping protocols, which you'd need to determine and document. The standardized approach is effective because it focuses on the position of the powder in the pre- and post- solution mixing phases and thus addresses—in part—the variability of the formulation and the rate and method of solution addition, as well as the configuration of the impeller and vessel. Plus, it's much simpler and reliable than devising an equation or model that accounts for all the possibilities of endpoint determination. In fact, I think a one-size-fits-all model is impractible given the variables involved. With physical standardization, however, it's pos- sible to overcome myriad problems regardless of the many variables, including the different impellers employed, some of which are shown above. Physical standardization is also superior to another common practice: Adding a fixed amout of granulating solution at a fixed rate and not allowing additional incre- ments. While that works sometimes, it's usually a futile attempt to achieve a mythical fixed endpoint. Even when precise additions aren't possible, as is the case when starch- based excipients are used, operators who are too focused on adding an exact quantity are not paying enough atten- tion to incremental additions and the overall process. Furthermore, many companies fix the interval at which a post-solution addition can be made, which presumes that the process doesn't vary according to the total amout of solution that might be added. In summary, an alternative approach to resolving the traditional problems associated with high-shear powder granulation is gaining traction, especially among overseas generic manufacturers. It warrants our attention and, if it provides more reliable, reproducible results, our support. T&C Fred A. Rowley is the owner and chief lecturer at Solid Dosage Training, 497 Phoenix Circle, Vallejo, CA. 94589. Tel. 925 352 5724. Website: www.soliddosageindia.com. Rowley is also an editorial advisor to Tablets & Capsules. Many factors affect how different formulations perform during wet granulation. If splattering is a problem, develop scraping protocols and document them. The equipment you use—including the impeller's configuration— affects how the granulation process performs. Download any T&C article for FREE! NewYear! Visit Our Website! www.tabletscapsules.com