Dragee production: everything from a single source

Granulation

This process step can be carried out in different ways, depending on the desired outcome. If the objective is to create a granules-based dragee core, batch granulation can be achieved using a combination of a high-shear mixer and fluid bed processor, or fluid bed granulation, or high-shear granulation in a one-pot system including vacuum drying.  All three, respectively four, granulation methods are suitable to produce a granule-based dragee core. For a granule & pellet-based core not dry but moist granules are required for extrusion and spheronization. For this reason, only granulation in a high-shear mixer can be considered (all other methods mentioned include drying). 

DIOSNA offers all of these options. High-shear mixing and granulation technology produces granules of remarkably high homogeneity and quality in a matter of minutes supported by the specific conical-cylindrical architecture of the DIOSNA’s P-line vessels and their two mixing tools. 

Wet granulation is initiated by adding the granulating solution and completed by reaching the determined end points which can be simply or very specifically. A basic feature of a DIOSNA High-Shear granulators is comprised of software and a variety of measuring parameters. The validated program is capable of calculating a range of data and key figures derived from the measured values like temperature, peripheral speed of the mixing tool, Froude number (needed for scale-ups), active power, total energy consumption, torque, power curve inflection point. Should the adjustable maximum values are for power and torque be exceeded, warnings or alarms are triggered, thereby advancing the mixing program.

Followed by this process prior drying the moist granulate is wet-sieved. For sizing the wet mass specified intermediate equipment such as the Kemutec Conemill generates a homogeneous mass of granules which then can be conveyed to a fluidized bed dryer (either directly or via a bulk container). This helps to uniform granules in size and thereby increasing the overall surface area, thus reducing the subsequent drying time.

Segregation

Subsequent to the drying process the next intermediate step is to de-agglomerate the lumps of the dry granulate e.g. by the previously mentioned cone mill prior passing it to a free-fall mixer or tumbler for final mixing before pressing. 

Pressing the dragee core

Finally, the granulate is transferred to an IBC. If allowed by the ceiling height of the production side, the IBC can be placed on top of a feed device, which is used to supply the tablet press. If the height for this is not available, the IBC contents can be conveyed using Coperion pneumatic conveyors directly to the feed frame of the tablet press. 

Coating 

The pressed cores will be released in a container and transported to a coater. Gabler provides un-perforated, onion shaped pan coaters. The application of the coating solution occurs by means of a high-pressure spray system, resulting in precise dosing of the application solution. Supply air is conditioned, and air volumes reach approx. 1200m³/h. 

Semi-continuous processing

There is a range of options for dragee production. Besides the former described batch process there are also semi-continuous solutions. Coperion,Gabler, and Mucon also offer solutions for continuous and semi-continuous production. The gravimetric loss-in-weight feeders, the vibratory feeders, as well as continuous pneumatic conveying including receivers, valves etc., are globally used for continuous applications.  

Furthermore, Coperion provides continuous hot-melt extrusion and wet extrusion. Hot-melt extrusion allows for a solvent-free production of solid dispersions or solids solutions of APIs (also BCS class 2 & 4), thus enhancing their bioavailability. This presents a particular advantage for APIs whose crystalline structure previously made this difficult. After extrusion the wet mixture is milled and cooled before pressing.