Pharmaceutical Manufacturing Handbook: Production and

1192 ORAL EXTENDED-RELEASE FORMULATIONS
the drug release. To understand the literature within the area of modifi ed drug
release, it is important to be aware of the standard terms used for dosage forms
within this fi eld. Malinowski and Marroum have summarized these terms in
the book Encyclopedia of Controlled Drug Delivery [1] . The authors state that
modifi ed - release (MR) formulations refer to “ dosage forms for which the drug
release characteristics of time course and/or location are chosen to accomplish
therapeutic or convenience objectives not offered by conventional dosage forms. ”
One group of MR formulations is the delayed - release dosage form, which does not
release the drug immediately after administration. One example of delayed - release
formulation is the enteric - coated formulations. Another subgroup of MR formulations
is the extended - release (ER) dosage forms, which are the focus of the present
chapter. According to a defi nition from the U.S. Pharmacopeia (USP), ER formulations
can be referred to as dosage forms that allow at least a twofold reduction in
the dosing frequency compared to conventional dosage forms [2, 3] .
The interest in oral ER formulations has dramatically increased in recent years.
This can be seen in Figure 1 , where the bars in the diagram correspond to the
number of publications found in a search in the database SciFinder Scholar 2006
[4] that include the words oral extended release . This increase in publications confi
rms that there are many ongoing activities in this fi eld. The expression oral extended
release occurs in the database for the fi rst time in 1954, when Yamanaka et al. utilized
the slow dissolution rate of various salts of a drug (pyrimidine penicillin) to
extend the period of time when the drug had a clinical effect [5] . In 1959 Robinson
and Suedres made a formulation of sulfamethylthiadiazole together with hydrogenated
castor oil, which was suspended in an aqueous vehicle, creating a formulation
with extended drug release [6] . Later, in the late 1950s and early 1960s Sj ö gren and
Frykl ö f compressed active substances (e.g., pentobarbitone sodium and theophyl-
Number of publications
2000
1800
1600
1400
1200
1000
800
600
400
200
0
2001–
2005
1996–
2000
1991– 1986– 1981–
1995 1990 1985
1976–
1980
Five-year periods
1971–
1975
1966–
1970
1961–
1965
>1960
FIGURE 1 Number of publications containing the words “ oral extended release ” identifi ed
in the database SciFinder Scholar 2006 for the fi ve - year period 1960 – 2005 [4] .