ABSTRACT
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.
