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CHAPTER 9 - Solid Oral Modified-Release Dosage Form and Drug Delivery Frequency reduction in dosing
Systems – extended-release products frequently deliver more than less
often than conventional form DepoFoam Drug Delivery System
INTRODUCTION
Enhanced convenience and compliance
Describes solid oral dosage forms and drug delivery system that – with less frequency in dosing, a patient is less apt to neglect
virtue of formulation and product design have modified drug taking a dose, also it provides greater convenience with day and
release features night administration
Modified release products provide either delayed release or Reduction in adverse side effects
extended release of drug – because of fewer blood level peaks outside therapeutic range
and into toxic range, adverse side effects are less frequent
Most delayed release products are enteric-coated tablets or
capsules designed to pass through the stomach unaltered, later to
Reduction in overall health care costs
release their medication within the intestinal tract
– overall cost of treatment may be less because of enhanced
therapeutic benefit, fewer side effects, and reduced time for
Enteric coatings are used either to protect a substance from
health care personnel to dispense and administer drugs and
destruction by gastric fluids or to irritating drugs
monitor patients
TERMINOLOGY
1. Sustained Release (SR) – Melatonex
2. Sustained Action (SA) – Drixoral
3. Extended Release (ER) – NOX3
4. Long Acting (LA) – Theraflu
5. Prolong Action (PA) –
6. Controlled Release (CR) – Melatonin
7. Timed Release (TR) – Vit-Min 100
Extended release products are designed to release their medication in a
controlled manner at a predetermined rate, duration, and location to
achieve and maintain optimum therapeutic blood levels of drug
a free flowing powder; commonly used to provide the hydrophilic Osmotic drug core Deliver orifices
matrix
A successful hydrophilic matrix system must contain the
following:
Delivery orifice
polymer must form a gelatinous layer rapidly enough to protect
the inner core of the tablet from disintegrating too rapidly after Water Water
ingestion
20% of HPMC results in satisfactory rates of release for an
extended-release tablet formation (e.g Oramorph SR Tablet)
Rate controlling Polymeric osmotic
Semipermeable Osmotic core membrane push compartment
membrane containing drug
Manufacturers may prepare two-layer tablets A. Elementary OROS osmotic B. OROS Push-Pull Osmotic System
one layer containing the uncombined drug for immediate release pump drug delivery system
OSMOTIC PUMP
they may also prepare a three-layer tablets
the pioneer oral osmotic pump drug delivery system is the Oros
outer layers containing the drug for immediate release
system developed by Alza
some commercial tablets are prepared with an inner core
composed of a core tablet surrounded by a semipermeable
containing the extended-release portion of the drug and an outer
membrane coating having a 0.4mm diameter hole produced by
shell containing drug for immediate release
laser beam. Example: Acutrim
core tablet has two layers, one containing the drug and the other
containing a polymeric osmotic agent
EMBEDDING DRUG IN INERT PLASTIC MATRIX
the system is designed such that only a few drops of water are
Drug is granulated with an inert plastic material such as
drawn into the tablet each hour
polyethylene, polyvinyl acetate, o polymethacrylate and the
function of the tablet depends on the osmotic gradient between
granulation is compressed into tablets
the contents of the two-layer core and the fluid in the
released from the inert plastic matrix by diffusion
gastrointestinal tract
retains its shape during leaching of he drug and during its passage
through the alimentary tract
Drug release rate may be altered by:
Example: Gradumet
changing the surface area
thickness
COMPLEX FORMATION
composition of the membrane and/or diameter of the drug
form complexes that may be slowly soluble in body fluids,
release orifice
depending on the pH of the environment
Extended release MOST COMMON PROCESS FOR DEVELOPING IVIVC MODEL (LEVEL A)
Diltiazem extended-release capsules develop formulations with different release rates or a single
Disopyramide phosphate extended-release capsules release rate if dissolution is independent of condition
Isosorbide dinitrate extended-release tablets and capsules obtain in vitro dissolution profiles and in vivo plasma
Propanolol hydrochloride extended-release capsules concentration profiles for these formulations
Theophylline extended-release capsules
estimate the in vivo absorption or dissolution time course for Propriety Modified-Release Oral Dosage Forms
each formulation and subject using appropriate mathematical Delayed-release
approaches
for vivo studies, human subjects are used in the fasted state
unless the drug is not well tolerated, in which case the studies
may be conducted in the fed state. Acceptable data sets have
been shown to be generated with use of 6 to 36 human subjects
Extended-Release Coated Particles and Breads
crossover studies are preferred, but parallel studies or cross-study
analysis may be acceptable using a common reference treatment
product, such as an intravenous solution, an aqueous oral
solution, or an immediate-release product
LABELING
they must be specific for the monograph article
aspirin delayed-release tablets must state that the tablets are
enteric coated
capsules must indicate whether the product is intended for
dosage every 12 to 24 hours and state which in vitro drug release
test the product complies
CLINICAL CONSIDERATIONS
not to be used interchangeably
or concomitantly with immediate-release
forms of the same drug
patients using a modified
release product should not be changed
into immediate release without
consideration to the blood concentration
patients should not be changed
Extended-Release Inert Matrix
to another extended-release product unless there is assurance of
equivalent bioavailability
different product can result in a marketed shift in the patient’s
drug blood level because of differences in drug release
characteristics
modified release tablets and capsules should not be crushed or
chewed
patients if fed through the nasogastric tube may receive modified-
release medications
nonerodible plastic matrix shells and osmotic tablets remain
intact throughout gastrointestinal transit and the empty shells or
ghosts from osmotic tablets may be seen in the stool
Extended Release Hydrophilic/Eroding Matrix
Extended-Release Osmotic