Pharmaceutical Manufacturing Handbook: Production and

RELEASE OF DRUGS FROM CONTROLLED-RELEASE DOSAGE FORMS 373
release of the drug is the polymer layer surrounding the reservoir. Since this polymer
coating is essentially uniform and of a nonchanging thickness, the diffusion rate of
the active agent can be kept fairly stable throughout the lifetime of the delivery
system.
For the diffusion - controlled systems ddescribed thus far, the drug delivery device
is fundamentally stable in the biological environment and does not change its size
through either swelling or degradation [4] . It is also possible for a drug delivery
system to be designed so that it is incapable of releasing its agent or agents until it
is placed in an appropriate biological environment. Swelling - controlled - release
systems are initially dry and, when placed in the body, will absorb water or other
body fl uids and swell. The swelling increases the aquenous solvent content with the
formulation as well as the polymer mesh size, enabling the drug to diffuse through
the swollen network into the external environment. Most of the materials used in
swelling - controlled - release systems are based on hydrogels, which are polymers that
well without dissolving when placed in water or other biological fl uids.
5.1.10.1 Time - Controlled - Release Dosage Forms
To achieve a drug release which is independent of the environment (e.g., pH, enzymatic
activity, intestinal motility), the lag time prior to the drug release has to be
controlled primarily by the delivery system. The release mechanisms employed
include bulk erosion of polymers in which drug release by diffusion is restricted,
surface erosion of layered devices composed of alternation drug - containing and
drug - free layers, osmotically controlled rupture, and enzymatic degradation of liposomes.
The device environment may modulate the release profi le of any of these
systems and may depend on factors such as the amount of free moisture, regional
blood fl ow, and various cellular activities at the site [88, 89] .
Systmes with Eroding or Soluble Barrier Coatings These types of delivery systems
comprise reservoir devices coated with a barrier layer. the barrier dissolves or
erodes after a specifi ed lag period, after which the drug is released rapidly from the
reservoir core. In general, the lag time prior to drug release from a reservoir - type
device can be controlled by the thickness of the coating layer, for example, the
Chronotropic systems, which consists of a drug - containing core layered with hydroxy
propyl methyl cellulose (HPMC), optionally coated with an outer enteric coating.
The lag time prior to drug release is controlled by the thickness and the viscosity
grade of the HPMC layer. After erosion or dissolution of the HPMC layer, a distinct
pulse was observed. The Chronotropic system [90, 91] is an oral dosage form designed
to achieve time - controlled delivery. This system has been developed keeping in mind
the interaction between GI fl uid and coating polymer, which causes time - or site -
controlled release. The reaction causes the liberation of drugs by the mechanism of
swelling of polymer, increased permeability, and dissolution/erosion phenomena.
This system probably works better for poorly water soluble drug because highly
water soluble drugs could diffuse through the swollen HPMC layer prior to complete
erosion.
The TIME CLOCK system for the oral dosage should enable fast and complete
release of drug after a predetermined lag time [92] . A tablet was made containing
the drug molecule and bulking agents (lactose, polyvinlpyrrolidine, corn starch, and