Scaling of the Granulation Process in the Conditions of GMP Training Center and Assessment of Possible Risks

. The stage of wet granulation is often used in the technology of solids. The method of wet granulation in a mixer-granulator with high shear force can be regarded as the most complicated method of its implementation from the engineering and technological point of view. The mixer-granulator has two mixers located in mutually perpendicular planes. Using an impeller, dry components are mixed, and the chopper, turning on when spraying a humidifier, ensures the formation of granules. By setting different chopper rotational speed, granules of different sizes can be obtained. This granulator has the following advantages: it provides a high product yield (≥ 99 %), takes up small workspaces, and the closed design ensures environmental protection. Aim . The aim of the research is to scale the granulation process, on the example of the solids production technology, using the wet granulation stage - in a mixer-granulator with high shear force. Materials and methods . Dry extract «N» and auxiliary substances were used as a pharmaceutical substance: lactose monohydrate, microcrystalline cellulose (MCC) (MICROCEL® MC-102), potato starch, povidone (Plasdone™ K-29/32), calcium stearate. Granulate under scaling conditions was produced in a mixer-granulator with high shear force. Technological properties of dry extract «N» and granulate were determined by the methods described in National pharmacopeia XIV. Results and discussion . On the basis of experimental studies, it was found that the resulting granulate, both when obtained under laboratory conditions and under scaling conditions, has good flowability, and also has a homogeneous fractional composition. The presence of a grinder in the mixer-granulator made it possible to obtain a more uniform fractional composition of the granulate. A 10-fold increase in loading did not affect the composition of the granulate. When scaling the pelletizing process, a risk analysis was carried out, factors influencing the technological process were identified and structured. It turned out that the most important stages are mixing and the actual granulation. To obtain a homogeneous mixture, additional equipment was used - a mixer. Conclusion . As a result of scaling up the granulation process, the parameters of wet granulation in the mixer-granulator (optimal loading, impeller and grinder rotation frequency), technological properties of the resulting granulate, and risks affecting the technological process were selected. were evaluated and a causal diagram (Ishikawa diagram) was drawn.