Simply put, extrusion spheronization is the process of converting wetted powders into spheres, also known as pellets, of a controlled shape and size.
Extrusion Spheronization is used as a manufacturing technique in the pharmaceutical industry for production of solid oral dosage forms but is also utilized in a number of other industries where a uniform pellet with controlled characteristics are desired including specific agrochemical, catalyst, and specialty chemical applications.
Powders often have poor flow characteristics that make them difficult to handle. Examples of issues include trouble with dosing, feeding, conveying, or segregation of mixtures. Having material in a uniform pelleted form greatly alleviates these issues.
Pellets produced using extrusion spheronization have a narrow particle size distribution as compared to other techniques. Control and uniformity are important characteristics when formulating an oral solid dosage form, and the process of extrusion spheronization allows formulators and drug manufacturers to produce pellets with a narrow particle size distribution.
In many applications coating the pellets is desirable to produce a specific release profile, taste mask, or to improve appearance. Extrusion and spheronization produces a pellet with a smooth, uniform surface which is necessary for effective coating.
Friability describes the tendency of a solid substance to break down from contact into smaller particles. It is important that pellets maintain their shape and size when being handled so that physical and therapeutic characteristics of the pellets are consistent from their initial formation through processing into the final form. It also is key to achieving higher process yields. Extrusion and spheronization produces a low friability pellet.
The consistent particle size and spherical shape obtained with extrusion spheronization provides uniform packing characteristics. This allows for easier handling downstream and is important for achieving consistency in the final dosage form.
Drug pelleting with extrusion spheronization allows you to achieve high drug loading of your active pharmaceutical ingredient (API) in a small pellet. Up to 90% API concentrations are possible with spheres produced using extrusion spheronization depending on the specific API. High drug loading can allow for fewer and/or smaller doses resulting in better patient compliance.
With extrusion and spheronization pellets the active pharmaceutical ingredient is equally distributed through a high number of individual pellets. These small pellets are able to evenly disperse and release into the gastrointestinal tract in a predictable and controlled fashion. This protects against the phenomenon of dose dumping, which can result in harmful side effects. The even dispersal of API through many particulates also facilitates maximum drug absorption.
Extrusion and spheronization pellets can be utilized in a variety of final dosage forms including capsules, tablets, sachets, and oral suspensions. The pellets produced using extrusion and spheronization can also be used to create more novel final oral solid dosage forms as well. The combination of incompatible API’s and higher and delayed dosage forms of a given API have been possible using extrusion and spheronization pellets. These novel uses may improve patient compliance and improve upon the safety and efficacy of the final oral solid dosage form.
Extrusion spheronization is capable of producing up to 300 kg/h of pellets for most pharmaceutical applications. Typically this allows for pellet production that is significantly faster than the production rate of a comparable drug layered pellet.
While extrusion spheronization is a multi step process it can be run as an integrated system in a continuous manner. Running in a continuous manner reduces the level of operator intervention and variability and can improve overall yield. There is also greater safety with a fully contained process.
The extrusion spheronization process consists of four main steps:
The first step in the extrusion spheronization process is mixing. A homogenous wet mixture is created with API, excipients, and solvent (typically water) normally in a high shear granulator. Modified release excipients can be integrated into the formulation in this wet mixing step. The wet mass generated in this process needs to be able to hold its shape under pressure but also have enough gliding properties to enable low pressure extrusion.
The next step in the process is extrusion. The homogenous wet mass that was prepared in the mixing step is metered into the hopper by a feeder into the twin screw extruder. The wet mix is transported to the extrusion zone where it is wiped through a dome die (or screen) to produce well formed, cylindrical extrudates of a controlled diameter. The extrudates break off by their own weight and are collected for the next processing step.
Spheronization is the step in the process where the extrudates are transformed into spherical pellets of a controlled shape and size. The extrudates are dropped onto a spinning friction plate, and the collisions of the pellets with the wall, plate, and each other round the cylindrical extrudates into spheres.
The final step is to dry (and coat as needed) the spheres to create the desired final characteristics for the solid oral dosage form.
LCI has a broad range of pelleting technology supported by a team of process experts and a test center where you can validate your solution. Would your product perform better as a pellet? Speak with an engineer about your process goals to get started on a solution.
