MODIFIED RELEASE

DOSAGE FORM

by
Rebin Sulaiman

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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
5 pharmaceuticals
1. Drugs that are not inherently long lasting require
multiple daily dosing to achieve the desired therapeutic
effects.

2. Multiple daily dosing is often inconvenient and can

result in missed doses, made-up doses and patient non-
compliant with therapeutic regimen.

3. Blood levels of drugs from conventional immediate-

release dosage forms taken more than once daily
following definite schedule usually demonstrate
sequential peaks and troughs (valleys) associated with
each dose.
4. Extended release tablets or capsules are commonly
taken only once or twice daily compared with the
conventional dosing of 2 to 4 times daily
6 • 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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7 Advantages of Extended-release Dosage
Forms over Conventional Forms

1. Reduction in drug blood level fluctuations

2. Reduction in frequency of dosing

3. Enhanced patient compliance

4. Reduction in incidence of adverse side effects

5. Reduction in overall healthcare costs.

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Terminology
• The following terms have been applied to
“extended” or “sustained” drug delivery
systems:
1. Controlled-release (CR)
2. Extended release (ER)
3. Sustained-release (SR)
4. Timed-release (TR)
5. Long-acting (LA)
6. Prolonged-action (PA), and
7. Sustained-action (SA)
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 Extended-release dosage forms
9

 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. bi-layered 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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 13 Extended-release Oral Dosage Forms

• The general properties of drugs best suited for ER

product design are:
1. They exhibit neither very slow nor very fast rates of
absorption and excretion

2. They are uniformly absorbed from the g.i.t.

3. They are administered in relatively small doses.

4. 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 un-coated

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 -
16 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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18 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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