ABSTRACT
The process of extrusion/spheronization originated in Japan and was introduced into
Europe and the United States in the early 1960s as the process of “Maurumerization,”
which was the trademark of the Fuji Denki Koyo Co Ltd. Eli Lilly & Co sold them under
license and the first description in the literature by Reynolds (1) in Europe and Conine
and Hadley (2) in the United States were from this company. The advantages for
the process listed by Reynolds (1) were “regularity in shape, consistency of size, definite
surface characteristics, low friability, flexible in respect of sphere size which can be
produced, capable of high throughput and easy operation.” These claims can still
be justified in most instances and the ability to produce pellets with relatively high drug
load, up to þ80% and the ability to carry out formulation studies on relatively small samples of material, can be added. The claim to the flexibility of possible sizes does not
mention the possible range and in practice, it is quite limited. For example, Clarke et al.
(3) found that while pellets in the range of 0.5-5.0mm could be prepared on a small
scale, the preparation of such a range on a large scale would be very difficult. At the
lower end, it is difficult to provide uniform holes of less than 0.5mm in diameter, which
are rigid enough to withstand the extrusion forces. It is also difficult to provide sat-
isfactory formulations that would extrude through such dies. At the upper end, there is
very limited information as to how larger diameter extrudate functions. There is work by
Rough and Wilson (4) with 3-mm dies, but some of the products are hardly of suitable
quality. A range of about 0.7-2.5mm is a more realistic range. While several major
pharmaceutical products are made by this process, even their scale is dwarfed by the
requirements of other industries. I was once asked to advise a chemical company who
wished to produce in 1 day what would have represented the annual production of a major
pharmaceutical product. Also, the fact that the process involves several stages requiring
different pieces of equipment and is difficult to convert to a fully continuous process, has
lead to some limitation of the application of the process. There is a recent publication
titled “Evaluation of the performance of a new continuous spheronizer” would indicate
that this had been solved (5). The paper, however, only describes its use as a batch
process and the information as to how it would be used in a continuous mode is scanty.
On a manufacturing scale, the process, therefore, must be considered as a batch process.
