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Presented by:

Zelica Trina Santos


Extended-Release Dosage Form
Consider:
Drug
Therapeutic indication
DRUG CANDIDATES FOR EXTENDED-
RELEASE PRODUCTS
To be successful, drug must be:
Released from dosage form at predetermined rate

Dissolve in gastrointestinal fluids

Maintained at sufficient gastrointestinal residence time

Be absorbed at a rate that will replace the amount of drug
being metabolized & excreted
Characteristics of Extended-Release
Products:
Exhibit neither very slow nor very fast rates
of absorption & excretion


Not necessary:
Drug w/ slow rates of absorption &
excretion
Poor candidates:
Drugs w/ short half lives, less than 2 hours
Drugs that act by affecting enzyme systems

Characteristics of Extended-Release
Products:
Uniformly absorbed from g.i.t
Drug must have:
Good aqueous solubility
Maintain adequate residence time in g.i.t

Poor candidates:
Poorly absorbed drugs
Drugs at varying & unpredictable rates
Characteristics of Extended-Release
Products:
Administered in relatively small doses

Not suitable:
Drugs w/ large single doses
Characteristics of Extended-Release
Products:
Posses a good margin of safety

Therapeutic Index
most widely used measure of the margin
TD50/ED50
Very potent drugs = narrow/very small
therapeutic index
Larger therapeutic index = Safer drug

Poor candidate:
Drugs administered in small doses/
possess very narrow therapeutic
indices
Characteristics of Extended-Release
Products:
Used in the treatment of chronic rather than
acute condition

Cause:
Drugs for acute condition = greater adjustment of the
dosage by physician

EXTENDED-RELEASE TECHNOLOGY
FOR ORAL DOSAGE FORMS

Extended drug action achieved by:

Affecting the rate (drug release from dosage form)
Slowing the transit time of dosage form through g.i.t
EXTENDED-RELEASE TECHNOLOGY
FOR ORAL DOSAGE FORMS
Technologies
modify rate of drug release from solid dosage
forms

Based on:
a) Modifying drug dissolution by controlling access of
biologic fluids
b) Controlling drug diffusion rates from dosage forms
c) Chemical reaction/interaction between the drug
substance of its pharmaceutical barrier & site-specific
biologic fluids
COATED BEADS, GRANULES, &
MICROSPHERES

Drug distributed onto:
Beads
Pellets
Granules
Other particulate
systems






Commercial Examples
Toprol-XL

(metoprolol succinate) tabs. (Astra);









Indocin SR

(indomethacin capsules (Merck);





COATED BEADS, GRANULES, &
MICROSPHERES

Conventional pan coating / air suspension coating
- a solution of drug
substance is placed on small inert
nonpareil seeds/ beads made of
sugar & starch or on microcrystalline
cellulose spheres

Nonpareil seeds 425 to 850 um

Microcrystalline cellulose spheres
- 170-600 um
- more durable during
production than
sugar-based cores

COATED BEADS, GRANULES, &
MICROSPHERES
Large dose
starting granules may be composed of drugs itself

Uncoated granules
immediate drug release

Varying Coated Granules
Lipid materials like beeswax, carnauba wax, glyceryl
monostrearate, or cetyl alcohol or a cellulosic material
like ethylcellulose

Careful blending of granules w/ different coating
thicknesses
Provide desired drug-released characteristics






COATED BEADS, GRANULES, &
MICROSPHERES
Colored coating
Distinguish granules/beads of different coating thickness

Place in capsules/ formed into tablets
Properly blended granules

COATED BEADS, GRANULES, &
MICROSPHERES
Various commercial aqueous coating systems use:
Ethylcellulose
plasticizer

Surelease [Colorcon]
Aquacoat [FMC
Corporation]
Aqueous coating systems eliminates hazards &
environmental concerns
COATED BEADS, GRANULES, &
MICROSPHERES
Thicker coat
more resistant to penetration
more delayed drug release & dissolution
Coated beads
1mm in diameter
Combined to have 3 or 4 release groups among the more than 100
beads contained in the dosing unit



Provide desired different rates of
sustained or extended release &
targeting of the coated beads to desired
segement of g.i.t
Spansule
(SmithKline
Beecham) capsule
MULTITABLET SYSTEM
Preparation of small spheroid compressed tablets 3-4mm
in diameter
To have varying drug release characteristics

Then, may be placed in gelatin capsule shells
- To provide the desired pattern of drug release

Each capsule
- 8-10 minitablets
- Some uncoated = immediate release
- Some coated = extended drug release
MICROENCAPSULATED DRUG
Microencapsulation
- A process by which solids, liquids, or even gases may be
enclosed in microscopic particles by formation of thin
coating of wall material around the substance

Late 1930s
- Cleaner substitute for carbon paper & carbon ribbons

1950s
- Ultimate development of reproduction paper & ribbons that
contained dyes in tiny gelatin capsules released on impact by
typewriter key or the pressure of a pen/pencil

Stimulus for development of a host of microencapsulated materials.
Including drugs
MICROENCAPSULATED DRUG
Gelatin
Common wall forming material, and synthetic polymer such as:
Polyvinyl alcohol
Ethylcellulose
Polyvinyl chloride
MICROENCAPSULATED DRUG
Typical encapsulation process:
1. Dissolve the wall material
Gelatin in water
2. Addition of material to be encapsulated
3. Two-phase mixture thoroughly stirred
4. Addition of a solution of a 2
nd
material to the desired particle
size of the material to be encapsulated
Usually Acacia
Additive material concentrates the gelatin (polymer) into tiny
liquid droplets
Droplets(coacervate)
- Form a film/coat around the particles of the substance to be
encapsulated
- Consequence of low interfacial tension of residual water/solvent in the
wall material
- To have continuous tight film coating






MICROENCAPSULATED DRUG
Final Dry Microcapsules:
Free flowing discrete particles of coated material
Wall material 2% to 20% of total particle weight

To obtain different rates of drug release:
Change ratio of core to wall, the polymer used for coating, and
method of microencapsulation


MICROENCAPSULATED DRUG
Advantage:
Administered dose of drug is subdivided into small units that are
spread over a large area of the g.i.t

Enhance absorption by diminishing local drug
concentration

Potassium Chloride
(Micro-K Extencaps, A.H.
Robins)