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EXTENDED-RELEASE ORAL DOSAGE FORMS Presented by:Zelica Trina Santos

Extended-Release Dosage Form

Consider:DrugTherapeutic indication

DRUG CANDIDATES FOR EXTENDED-RELEASE PRODUCTSTo 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


• Uniformly absorbed from g.i.t Drug must have:Good aqueous solubilityMaintain adequate residence time in g.i.t

Poor candidates:Poorly absorbed drugsDrugs at varying & unpredictable rates


• Administered in relatively small doses

Not suitable:Drugs w/ large single doses


• Posses a good margin of safetyTherapeutic Index

most widely used measure of the marginTD50/ED50Very potent drugs = narrow/very small

therapeutic indexLarger therapeutic index = Safer drug

Poor candidate:Drugs administered in small doses/

possess very narrow therapeutic indices


• 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 fluidsb) Controlling drug diffusion rates from dosage formsc) Chemical reaction/interaction between the drug

substance of its pharmaceutical barrier & site-specific biologic fluids

COATED BEADS, GRANULES, & MICROSPHERES

• Drug distributed onto:BeadsPelletsGranules Other particulate

systems

Commercial Examples• Toprol-XL® (metoprolol succinate) tabs. (Astra);

• Indocin SR ® (indomethacin capsules (Merck);


• 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


• 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:

Ethylcelluloseplasticizer

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 alcoholEthylcellulosePolyvinyl 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 stirred4. Addition of a solution of a 2nd 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 materialWall 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)

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