MODIFIED RELEASE DOSAGE FORM by A. S. Adebayo, PhD

MODIFIED RELEASE
DOSAGE FORM
by
A. S. Adebayo, PhD
Wednesday, January 11, 2017
1
Introduction

Modified release dosage forms are
drug delivery systems (DDS) which, by
virtue of formulation and product
design, provide drug release in a
modified form distinct from that of
the conventional dosage forms.
Drug release can either be delayed or
extended in nature.
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Delayed-release products

Usually enteric coated tablets
or capsules designed to pass
through the stomach unaltered
to release their medication
within the intestinal tract.
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Extended-release products

Designed to release their medication in
controlled manner, at pre-determined
rate, duration and location in the
body to achieve and maintain
optimum therapeutic blood levels of
drug.
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Rationale for extended release
pharmaceuticals

Drugs that are not inherently long lasting require
multiple daily dosing to achieve the desired
therapeutic effects.

Multiple daily dosing is often inconvenient and can
result in missed doses, made-up doses and patient
non-compliant with therapeutic regimen.

Blood levels of drugs from conventional immediaterelease dosage forms taken more than once daily
following definite schedule usually demonstrate
sequential peaks and troughs (valleys) associated
with each dose.
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Rationale for extended release
pharmaceuticals

Extended release tablets or capsules are
commonly taken only once or twice daily
compared with the conventional dosing of 2 to 4
times daily


Products are designed to provide an immediate release of
drug which promptly produces the desired therapy, followed by
gradual and continual release of additional amounts of drug to
maintain this effect over a predetermined period of time.
The need for night dosing of drugs may be
eliminated
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Advantages of Extended-release
Dosage Forms over Conventional
Forms

Reduction in drug blood level fluctuations

Reduction in frequency of dosing

Enhanced patient compliance

Reduction in incidence of adverse side effects

Reduction in overall healthcare costs.
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Terminology

The following terms have been applied to
“extended” or “sustained” drug delivery
systems:







Controlled-release
Extended release (ER)
Sustained-release (SR)
Timed-release (TR)
Long-acting (LA)
Prolonged-action (PA), and
Sustained-action (SA)
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Extended-release dosage forms
The US FDA defines ER dosage form
as:
one that allows a reduction in dosing
frequency to that presented by a
conventional dosage form such as a
solution or an immediate release
dosage forms.

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Delayed-release

These are dosage forms designed
to release the drug at a time other
than promptly after administration.

The delay may be time-based or
based on the influence of
environmental conditions such as
g.i. pH, enzyme, pressure, etc
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Repeat action

These are dosage forms usually
containing 2 single doses of
medication, one for immediate and the
second for delayed release e.g. bilayered tablets.
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Targeted release

Drug release that is directed
towards isolating or concentrating a
drug in a body region, tissue, or site
for absorption or drug action
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Extended-release Oral
Dosage Forms
The general properties of drugs best suited for ER
product design are:
 They exhibit neither very slow nor very fast rates of
absorption and excretion

They are uniformly absorbed from the g.i.t.

They are administered in relatively small doses.

They possess a good margin of safety i.e. Therapeutic
Index (TI)
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Technology of ER Dosage
Forms
ER Coated Beads, Granules or
Microspheres –
 Granules of drug may be coated with lipid
materials such as beeswax, carnuba wax,
glyceryl monostearate, cetyl alcohol, etc.

Careful blending of coated and uncoated granules and with coatings of
different thicknesses will provide drug
release of desired characteristics.
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COMMERCIAL EXAMPLES

Toprol-XL® (metoprolol succinate) tabs.
(Astra);

Indocin SR ® (indomethacin capsules
(Merck);

Compazine ® (prochloperazine) Spansule
Capsules (SmithKline Beecham)
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Technology of ER Dosage Forms Multitablet system
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Technology of ER Dosage
Forms

Embedding drug in slowly eroding or
hydrophilic matrix system – The design
comprises of the drug substance plus
excipient material that slowly erodes in body
fluids thereby progressively releasing the
drug for absorption

E.g. Quinidex® Quinine SO4 tablets (Robins);
Oramorph ® SR Morphine SO4 tabs. Roxane ®
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Technology of ER Dosage Forms:
ER Microencapsulated Drug

–Microencapsulation is a process by which solids,
liquid and semi-solid substances may be
encapsulated into microscopic size particles
through the formation of thin coating of “wall”
material around the substance.


Different rate of drug release can be obtained
by changing the core to wall ratio, the type of
polymer coat and the method of
microencapsulation.
E.g. K-Dur ®Microburst Release System (KCl)
tabs. (Key)
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Technology of ER Dosage
Forms: Osmotic pump device

This consists of a core tablet surrounded by
a semi-permeable membrane coating with a
0.4 mm diameter hole produced by laser
beam.

The core tablet has 2 layers, one containing
the drug (the “active” layer) and the other
containing the polymeric osmotic agent (the
“push” layer).


E.g. Glucotrol ® XL (glipizide) tablets (Pfizer)
Covera – HS ® (verapamil HCl) tabs. (Searle)
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Other methods

Embedding drug in an inert plastic
matrix – e.g. Desoxyn®
(methamphetamine HCl) tabs (Abbott);
Procanbid ® (procainamide HCl tabs.
(Parke-Davis)

Complex formation

Ion exchange resins
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Kinetics of Drug release

Drug release from conventional dosage
forms, like the other processes of ADME,
are governed by the first-order kinetics
model.

In First-order model, drug release is
dependent on the amount of drug available
for release and therefore the rate of
release declines exponentially with time.
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Kinetics of Drug release…

Extended release dosage forms are
governed by zero-order kinetics in which the
rate of release is independent of amount
of drug remaining in the dosage form.

Therefore a constant amount of drug will be
released over time from extended release
dosage forms
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Assignments (Due Feb. 4, 2010)

Identify 3 controlled release formulation excipients,
giving chemical and commercial names

What is the kinetic mechanism of drug release
followed by Osmotic controlled delivery devices?

Using a suitable graph, illustrate the profile that
would be observed in the following scenarios:



Burst release at peal plasma level
Design failure leading to “Dose dumping”
Design failure leading to drug being withheld
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MODIFIED RELEASE
DOSAGE FORM
THANK YOU FOR YOUR ATTENTION
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