Pharmaceutical Manufacturing Handbook: Production and

CONTROLLED-RELEASE FORMULATIONS 351
Different types of modifi ed release systems can be defi ned [4, 8] :
• Sustained release (extended release) that permits a reduction in dosing frequency
as compared to the situation in which the drug is presented as a conventional
form
• Delayed release when the release of the active ingredient comes sometimes
other than promptly after administration
• Pulsatile release when the device actively controls the dosage released following
predefi ned parameters
In general, the sustained - release dosage form is designed to maintain therapeutic
blood or tissue levels of the drug for an extended period of time. This is accomplished
by attempting to obtain zero - order release from the designed dosage form.
Zero - order release constitutes drug release from the dosage form that is independent
of the amount of drug in the delivery system at a constant release rate. Systems
that are designed for prolonged release can also be attributed as achieving
sustained - release delivery systems. Repeat - action tablets are an alternative method
of sustained release in which multiple doses of drugs are contained within a dosage
form and each dose is released at a periodic interval, while delayed - release systems
may not be sustaining, since often the function of these dosage forms is to maintain
the drug within the dosage form.
5.1.4 PHYSICOCHEMICAL AND BIOLOGICAL FACTORS
INFLUENCING DESIGN AND PERFORMANCE OF
CONTROLLED - RELEASE FORMULATIONS
A number of variables, such as drug properties including stability, solubility, partitioning
characteristics. charge and protein binding behavior, routes of drug delivery,
target sites, acute or chronic therapy, the disease, and the patient, must be considered
to establish the criteria for designing controlled - release products [9] . The performance
of a drug in its release pattern from the dosage form as well as in the body
proper is a function of its properties. These properties can at times prohibit placement
if the drug is in a controlled - release form, restrict the route of drug administration,
and signifi cantly modify performance for one reason or another. There is
no clear distinction between physicochemical and biological factors since the biological
properties of a drug are a function of its physicochemical properties while
biological properties result from typical pharmacokinetic studies on the absorption,
distribution, metabolism, and excretion (ADME) characteristics of a drug as well
as those resulting from pharmacological studies.
5.1.4.1 Physicochemical Factors
Physicochemcial properties, such as aqueous solubility, partition coeffi cient and
molecular size, drug stability, and protein binding, are those that can be determined
from in vitro experiments.