Extrusion/spheronization is a multiple-step process capable of making uni-

formly sized spherical particles commonly referred to as spheres or pellets.

The pellets produced using this method can be used for both immediate-

release or modified-release applications. They are typically filled into hard gelatin capsules, but can also be compressed into tablets. The major advantage

of extrusion/spheronization over other methods of producing drug-loaded

spheres or pellets is the ability to incorporate high levels of actives without

producing an excessively large particle. Additionally, the process is more

efficient than other techniques for producing pellets. Spheronization is a process invented by Nakahara in 1964. The U.S.

Patent (3,277,520) describes a ‘‘Method and Apparatus for Making Spherical

Granules’’ from wet powder mixtures or granulations [1]. The equipment

described in the patent was commercialized by Fuji Denki Kogyo Co. under

the trade name MarumerizerR. It is generically referred to today as a spheronizer. The process went widely unnoticed in the pharmaceutical

industry until 1970, when two articles were published by employees of

Eli Lilly and Co. Conine and Hadley [2] described the steps involved in

the process including (1) dry blending, (2) wet granulation, (3) extrusion,

(4) spheronization, (5) drying, and (6) optional screening. Reynolds [3] went

on to further describe the equipment and the mechanics of the process,

including the movement of the particles within the spheronizer, which results

in a characteristic ropelike formation. This phenomenon is an important

indicator in the formulation and process development and will be discussed

in greater detail. Both publications cite desirable attributes of spherical

particles that can be achieved. These attributes include good flow, low dusting, uniform size distribution, low friability, high hardness, ease of

coating, and reproducible packing. While it should be noted that the proper-

ties of spheres and pellets produced using this method can be drug-specific, they are generally reproducible even at high drug loading levels. Additionally,

they offer the common therapeutic advantages seen with multiparticulate drug delivery systems, such as a reduced risk of dose dumping in modified-release products, as well as less gastrointestinal irritation [4]. From the publication of

these articles up to today, the interest in extrusion/spheronization has

continued to grow. The process has become an established pelletization

technique with an increasing number of products currently being produced.

In the interim, the industry interest was primarily driven by the academe. The

increased popularity is, in part, due to the ease of processing and efficiency as compared to other common pelletization techniques such as spray or powder

layering. There is a growing understanding of the effects of process parameters and material characteristics. However, as suggested by Newton [5], the

preparation of pellets by extrusion/spheronization is still a technology without

complete understanding.