Hot melt granulation via twin-screw extrusion is a technology that allows for the continuous processing of pharmaceuticals. Continuous manufacturing has gained momentum recently, with a significant focus on continuous direct compression. However, certain formulations with manufacturability challenges, such as poor compaction and poor flowability, require a granulation process. The technique of twin-screw melt granulation can address challenging formulation and process issues with greater efficiency than other methods.

Twin-screw extrusion is an ideal platform for continuous granulation, especially for melt and wet granulation. An effective granulation process can present itself as a solution for certain formulation issues — including challenges that involve poor compaction or flow properties in a particle — and be applied to any class of small molecule API. By enhancing both flowability and compressibility, twin-screw melt granulation increases the efficiency of downstream processes, such as tablet compression or capsule filling.

The Advantages of Twin-Screw Melt Extrusion

Twin-screw melt granulation offers the benefits of continuous manufacturing — providing a reduced footprint and improved economics — but with a greater degree of process control, with consistent product quality achieved through the implementation of different process analytical technologies (PATs). Because twin-screw melt granulation is carried out at higher temperatures than traditional batch melt granulation, thermoplastic polymers can be used as binders. This is a clear benefit, considering the limited number of traditional binders that are suitable for use in conventional granulation processes.

The process of twin-screw melt granulation is also exceptional as it obviates the need for both solvents and water, which presents environmental and economic advantages. Additionally, since it is a totally water-free process, twin-screw melt granulation is suitable for drugs that undergo hydrolysis or degradation in the presence of water.

However, the main disadvantage of twin-screw melt granulation is the high temperatures that the process requires, which may degrade certain sensitive APIs. During the process, the drug is exposed to elevated temperatures in the range of 70–130 °C for 20–40 seconds. For customers who are seeking the benefits of melt extrusion but are apprehensive about putting their API through this process, it makes sense to rely on an outsourcing partner with deep experience employing this technology like Foster Delivery Science. 

Foster Delivery Science has over 30 years of experience working with twin-screw technology and are experts in the field. We have fielded cases when an API was not thought to be suitable for twin-screw processing because of thermal instability and overcame those challenges to blend the API and polymer without degrading the API. We have the knowledge and ability to design screw profiles that will allow for API stability during the intensive process — we also have the techniques and expertise needed to mitigate damage. 

Twin-Screw Melt Granulation and Commercial Success

The process of twin-screw melt granulation begins by adding ingredients, which can be pre-blended or fed independently. The ingredients then pass through granulation, using a custom screw designed for the specific formulation. The key process factors in twin-screw melt granulation are the screw speed, the feed rate and the temperature. Granulation is then followed by milling in preparation of the finished dosage form. This flexible process is variable insofar as it is dependent on the formulation.

As the process design must be tailored to match each specific formulation, the process can be changed throughout — this can mean altering the length of the process or the screw design. There are many different unit operations that take place in an extruder, which are largely determined by the elements within the screw design.

The most crucial step in twin-screw melt granulation is understanding the API characteristics, including its melting point, sensitivity and any other factors that might impact how it performs, as well as the desired end product characteristics. Once these factors have been fully determined, excipients are picked — the binder should melt and encapsulate the API. The process is amendable, allowing for additives to be included late in the process.

Experts with Experience

We are proud to announce that we just had a manuscript on the “Effects of Thermal Binders on Chemical Stabilities and Tabletability of Gabapentin Granules Prepared by Twin-Screw Melt Granulation” published in the International Journal of Pharmaceutics (559: 37-47 [2019]). This represents the headway we have made in the field and confirms our authority with regard to the process.