TERMINOLOGY

MODIFIED RELEASE
 Used to describe dosage forms
having drug release features
based on;
TIME – COURSE - LOCATION
that are designed to accomplish
therapeutic or convenience
objectives not offered by
conventional forms
Extended Release

Delayed Release

Repeat Action

Targeted Release
 TERMINOLOGY

EXTENDED-RELEASE
 This type of dosage form allows a
REDUCTION in DOSING FREQUENCY to
that presented by a conventional
dosage form.
 means the pill is formulated so that
the drug is released slowly over time.

Dimetapp Extentabs (AH Robins)

OTHER TERMS
sustained release(SR)
sustained action (SA)
prolonged action(PA)
controlled release (CR)
extended release(ER)
timed release (TR)
long acting (LA)
 TERMINOLOGY

DELAYED RELEASE
 This is designed to release the
drug from the dosage form AT
A TIME OTHER THAN promptly
AFTER ADMINISTRATION.
Examples: enteric-coated
tablets and enteric capsules
 DELAYED RELEASE
The release of a drug from an oral dosage form
may be intentionally delayed until it reaches the
intestines for several reasons.

- to protect a drug destroyed by gastric fluids,

- to reduce gastric distress caused by drugs
particularly irritating to the stomach.
- to facilitate GI transit for drugs which are better
absorbed from the intestines.

- Among the many agents used for enteric

coating of tablets and capsules are fats, fatty
acids, waxes, shellac, and cellulose acetate
phthalate
 DELAYED RELEASE

The enteric coating may be

pH dependent, breaking down in
the less acidic environment of the
intestine,
time dependent, eroding by
moisture over time during
gastrointestinal transit,
enzyme dependent, deteriorating
as a result of the hydrolysis-
catalyzing action of intestinal
enzymes.
 TERMINOLOGY

REPEAT-ACTION
Usually contain two doses of
medication, one for IMMEDIATE
RELEASE and the second for
DELAYED RELEASE or extended
release.
 REPEAT ACTION
 Repeat action tablets are prepared so that an initial
dose of drug is released immediately followed later by
a second dose.

 Immediate release -tablet’s outer shell or coating

 Second release-tablet’s inner core separated by a
slowly permeable barrier coating

 Drug from the inner core is exposed to body fluids and

release 4 to 6 hours after administration

 Repeat action dosage forms are best suited for the

treatment of chronic conditions requiring repeated
dosing.

 The drugs utilized should have low dosage and fairly

rapid rates of absorption and excretion.
 TERMINOLOGY

TARGETED RELEASE

 Describes drug release

directed toward ISOLATING or
CONCENTRATING a drug in a
body region, tissue, or site for
absorption or for drug action
 DRUG CANDIDATES FOR EXTENDED-
RELEASE PRODUCTS
1. Exhibit neither very slow nor very fast
rates of absorption and excretion
2. Uniformly absorbed from the GIT
3. Administered in relatively small doses
4. Good margin of safety (due to risk of
dose dumping)
5. For treatment of chronic rather than
acute conditions
Extended-release Technology of
oral dosage forms
a. Modifying drug dissolution by controlling
access of biologic fluids to the drug
through the use of barrier coatings
b. Controlling drug diffusion rates from
dosage forms
c. Chemical reaction or interaction
between the drug substance or its
pharmaceutical barrier and site-specific
biologic fluids
 Coated beads ,
granules and
microspheres

Complex Microencapsulati
formation on

Sustained
Release
Mechanism

Ion-Exchange
Matrix
Resin

Osmotic system
 The drug is distributed into beads,
pellets, granules or other particulate
system
 Drug is coated onto inert beads
(sugar, starch or microcrystalline
cellulose).
 The granule mixture: Uncoated
(immediate effect)and Coated pellets
may be filled into capsules or
compressed lightly into tablets
COATED BEADS, GRANULES, AND MICROSPHERES
 When drug dose is large-granules is used
 granules are coated with LIPID COATING
MATERIALS include beeswax, carnauba wax,
glyceryl monostearate, or cetyl alcohol or
cellulosic material like ethylcellulose
 Granules will be placed in capsules or tablets
 AQUEOUS COATING SYSTEMS are also used
as coating material such as ethyl cellulose and
plasticizer-Aquacoat and Surelease
 The thicker the coat the more resistant to
penetration more delay on drug release and
dissolution
Product Component Form

Ornade Spansule Phenylpropanolamine and Coated pellets in

Chlorpheniramine maleate capsule
(colds)

Toprol XL Metoprolol succinate 50 mg Pellets in tablet

(antihypertensive)
25mg

Indocin SR Indomethacin Coated pellets in

(Anti-inflammatory capsule
Analgesic)
Compazine Prochlorperazine Coated pellets in
spansule (anti-psychotic ) capsule
 Multitablet System
 Small spheroid compressing tablets 3 to 4 mm in
diameter
 Placed in gelatin capsule shell to provide the
desired pattern of drug release
 Each capsule contain 8 to 10 minitablets
 Uncoated for immediate release and other
coated for extended release
MICROENCAPSULATION
 Solids, liquids, or even gases may be ENCAPSULATED
into MICROSCOPIC-SIZE PARTICLES, through the
formation of thin coatings of “wall” materials around
the substance being encapsulated.

 Gelatin, polyvinyl alcohol, ethylcellulose, PVC are

examples of wall-forming materials

 The "wall" material (e.g. gelatin) is first dissolved in

water. the material to be encapsulated is added, and
then a second material, usually acacia, is added to
concentrate the gelatin into tiny liquid droplets. These
droplets coat the particles of the drug to be
encapsulated
Advantage
 The administered drug dose is subdivided into
small units spread over a large area of the GIT,
enhance absorption by diminishing local drug
concentration

Micro-K Extencaps potassium chloride potassium

Depletion

Effexor XR venlafaxine antidepressant

hydrochloride
Embedding Drug in Slowly Eroding or
Hydrophilic matrix system
 the drug substance is combined and made into granules with
an excipient material that slowly erodes in body fluids,
progressively releasing the drug for absorption.
 When these granules are mixed with granules of drug prepared
without the excipient, the uncombined granules provide the
immediate drug effect whereas the drug-excipient granules
provide extended drug action.
 Hydrophilic cellulose polymers (e.g. HPMC) are commonly used
as excipient base
 The granule mix may be formulated as tablets or capsules
Gastric fluid
Depakote ER Divaproex sodium antiepileptic
Quinidex quinidine sulfate antiarrhythmic
Oramorph SR morphine sulfate analgesic for severe
pain

Depakote ER Quinidex Oramorph SR

 Embedding Drug in Inert Plastic Matrix
 Embedding drug in an INERT PLASTIC MATRIX
such as polyethylene, polyvinyl acetate, or
polymethacrylate

 Drug is slowly released from the plastic matrix

by diffusion

 The inert tablet matrix, expended of drug, is

excreted with the feces
Ferro- Iron prep
Gradum
et
 COMPLEX FORMATION
 Drug substances are combined with other
chemical agent to form complexes that
may be only slowly soluble in body fluids,
depending on the pH of the environment
 The slow dissolution provides the extended
release of the drug
 Ex: Rynatan (Chlorpheniramine & phenylephrine)
antihistamine
ION-EXCHANGE RESINS
 A solution of a cationic drug may be passed through a column containing an
ion-exchange resin, forming a complex by the replacement of hydrogen
atoms.

 A complex of resin-drug is formed; tabletted, encapsulated or suspended in

an aqueous vehicle

 The release of the drug is dependent upon the pH and the electrolyte
concentration in the GIT

 Examples:

Hydrocodone polistirex and chlorpheniramine polistirie suspension

(Tussionex Pennkinetic Extended Release Suspension) cough preparation

Phentermine Resin Capsules (Ionamin)weight loss

OSMOTICALLY CONTROLLED SYSTEMS
 OROS SYTEM – pioneer oral osmotic pump delivery
system
 Composed of core tablet surrounded by a
semipremeable membrane coating have a 0.4mm
diameter hole produced by laser beam.
 Composed of a core tablet surrounded by a semi-
permeable membrane coating having a ”hole.”
 Core tablet:
(1) “ACTIVE” layer – containing the drug
(2) “PUSH” layer – containing the polymeric osmotic
agent
Osmotic Pump
System Orifice

Water

Drug Reservoir

Semipermeable membrane
30
The drug release rate may be
altered by
 Changing the surface area
 Thickness or composition of the membrane
 diameter of the drug release orifice

The drug release rate is not affected by

gastrointestinal acidity, alkalinity, fed condition
or GI motility

 The biologically inert components of the tablet

remain intact during gastrointestinal transit and are
eliminated in the feces as an insoluble shell.
 OSMOTIC SYSTEMS
 GITS (Gastrointestinal Therapeutic System)

Procardia XL
Glucotrol XL(Glipizide)
(Nifedipine)
diabetes
antihypertensive

Adalat GITS (nifedipine)

antihypertensive
COER (Controller-Onset Extended Release)
Covera-HS (verapamil hcl) hypertension
Other Osmotically Controlled Oral Products
Products Active Drug Uses
Calan SR Verapamil Antihypertensive
agent
Volmax Albuterol asthma
Minipress Prazosin Antihypertensive
XL agent
Teczem Enalapril and Antihypertensive
Diltiazem agent
Tiamate Diltiazem Antihypertensive
agent
Clinical
Considerations
❖ Patients should be advised of the dose and
dosing frequency of modified drug-release
products and instructed not to use them
interchangeably or concomitantly with
immediate-release forms of the same drug.
❖ Patients should be advised that modified- release
tablets and capsules should not be crushed or
chewed, since such action would compromise
their drug release feature
❖ Patients and caregivers should be advised that
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.
Packaging
 Well closed and tight container
 Light resistant container