The development of
T he technologies behind oral
drug delivery have emerged
from the mainstream pharma-
ceutical industry and have become
influential forces in their own right,
controlled-release as evidenced by the burgeoning
formulations continues “drug delivery companies” that are
to be a big success for the at the forefront of innovation and
pharmaceutical industry. hold their own niche market.
The success of any techno- Drug delivery companies and
logy relies on the ease of its their pharmaceutical industry part-
manufacturing process and ners are poised to reap the rewards
its reproducibility of of the multibillion-dollar drug
desirable biopharmaceutical delivery market, which is forecast
properties. to grow to about $70 billion by 2005
(1). The market for oral controlled
drug delivery alone is expected to
grow at 9% or more every year
through 2007. The driving forces
behind this booming market can be
divided into two main groups:
patient-related factors (see Table I
and Figure 1) and market-driven
factors.
Nandita G. Das, PhD,
is assistant professor of Market factors drive
pharmaceutics, ndas@ development
pharmacy.isu.edu and Sudip Drug delivery is a valuable drug life-
K. Das, PhD, is associate cycle management tool. The most
professor of pharmaceutics,
das@pharmacy.isu.edu, at
important force driving growth and
Idaho State University, College viability of the pharmaceutical
of Pharmacy, Pocatello, ID. industry, the regular introduction
of new molecular entities (NME),
10 Formulation, Fill & Finish 2003 Formulation, Fill & Finish 2003 10
Formulation, Fill & Finish
MEC
Figure 1.
Plasma drug
24 hours concentration
Time
profiles for
conventional
tablet or capsule formulation (– –) and a zero-order controlled-release formulation
( ___ ). MEC = Minimum Effective Concentration; MSC = Maximum Safe Concentration.
System) such that their absorption have gained steady popularity be-
rate is controlled exclusively by the cause of their simplicity in design.
rate of release from the dosage form The drawback of matrix-type deliv-
(3). It is only under these condi- ery systems is their first-order drug
tions that in vitro dissolution rates delivery mechanism caused by
can possibly be used to predict in changing surface area and drug dif-
vivo absorption rates and guide for- fusional path length with time. This
mulation development. drawback has been addressed by
osmotic delivery systems, which
Currently marketed oral maintain a zero-order drug release
controlled-release systems irrespective of the pH and hydro-
Advances in oral controlled-release dynamics of the GI tract. Multipar-
technology are attributed to the ticulate systems are gaining favor
development of novel biocompati- over single-unit dosage forms be-
ble polymers and machineries cause of their desirable distribution
that allow preparation of novel- characteristics, reproducible transit
design dosage forms in a repro- time, and reduced chance of gastric
ducible manner. The main oral irritation owing to the localization
drug-delivery approaches that have of drug delivery.
survived through the ages are as Although several technologies for
follows: the production of microparticulate
● Coating technology using various systems have been designed, thus far
polymers for coating tablets, non- the mainstream technologies are
pareil sugar beads, and granules still based on spray-drying, sphero-
● Matrix systems made of swellable nization, and film-coating technol-
or nonswellable polymers ogy. Textbook references mention
● Slowly eroding devices reservoir-type devices; however, be-
● Osmotically controlled devices. cause of the technical hurdles in
Conventional tablet formulations manufacturing reproducibility and
are still popular in the design of lack of safety and efficacy, true reser-
single-unit, matrix-type controlled- voir devices have not yet succeeded.
release dosage forms. The advance-
ment of granulation technology and FDA regulation of oral
the array of polymers available with controlled-release drugs
various physicochemical properties In the 1980s, FDA introduced rigor-
(such as modified cellulose or starch ous regulations governing bioequiv-
derivatives) have made the develop- alence and in vitro–in vivo correla-
ment of novel oral controlled- tions for controlled-release products.
release systems possible. Required pharmacokinetic evalua-
Matrix devices made with cellu- tions involve
lose or acrylic acid derivatives, ● relative bioavailability following