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Monday, August 26, 2013 1

MODIFIED RELEASE

DOSAGE FORM

by

A. S. Adebayo, PhD


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Introduction

Modified release dosage forms are

drug delivery systems (DDS) which, by

vi r tue of formulat ion and productdesign, provide drug release in a

modified form dist inct f rom that of

the convent ional dosage forms.Drug release can either be delayed or

extended in nature.


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Delayed-release p roduc ts

Usually enteric coated tablets

or capsulesdesigned to pass

through the stomach unal tered

to release their medicat ion

w ithin the intest inal tract .


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Extended-release produc ts

Designed to release their medication in

controlled manner, at pre-determined

rate, durat ion and locat ionin thebody to achieve and maintain

op t imum therapeut ic b lood levelsof

drug.


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Rationale for extended release

pharmaceuticals Drugs that are not inherently long lasting require

multiple daily dosing to achieve the desiredtherapeutic effects.

Multiple daily dosing is often inconvenient and canresult in missed doses, made-up doses and patientnon-compliant with therapeutic regimen.

Blood levels of drugs from conventional immediate-release dosage forms taken more than once dailyfollowing definite schedule usually demonstratesequential peaks and troughs (valleys) associatedwith each dose.


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Rationale for extended release

pharmaceuticals

Extended release tablets or capsules arecommonly taken only once or twice dailycompared with the conventional dosing of 2 to 4times daily

Products are designed to provide an immediate release ofdrugwhich promptly produces the desired therapy, followed bygradual and continual release of additional amounts of drug tomaintain this effect over a predetermined period of time.

The need for night dosing of drugs may beeliminated


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Advantages of Extended-release

Dosage Form s over Convent ional

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 al lows areduc t ion in dos ing

frequencyto that presented by a

convent ional dosageform such as a

so lut ion or an immediate releasedosage forms.


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Delayed-release

These are dosage forms designed

to release the drug ata t ime o ther

than prom pt lyafter adm inistration .

The delay may betime-basedor

based on the inf luence ofenvi ronmental cond i tionssuch as

g .i. pH, enzyme, pressure, etc


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Repeat action

These are dosage forms usually

containing 2 sing le dosesof

medication, one forimmediate and thesecond fordelayed release e.g. bi-

layered tablets.


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Targeted release

Drug release that is d irected

towards isolat ing or concentrat ing a

drug in a body region , t issue, or si tefor abso rpt ion or d rug act ion


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Extended-release Oral

Dosage Form s

The general properties of drugs best suited for ERproduct design are:

They exhibit neither very slow nor very fast rates ofabsorption 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. TherapeuticIndex (TI)


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Technology of ER Dosage

Forms

ER Coated Beads, Granu les orMicrospheres

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 ofdifferent thicknesses will provide drugrelease 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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Forms

Embedding drug in slowly eroding or

hydrophilic matrix system The design

comprises of the drug substance plusexcipient 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 ofwall

material around the substance.

Different rate of dru g release can be ob tained

by changing the co re to wal l rat io, the type of

polymer coat and the method ofmicroencapsulat ion.

E.g . K-DurMicroburst Release System (KCl)

tabs. (Key)


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Forms: Osmotic pump device

This consists of a core tablet surrounded bya semi-permeable membrane coating with a0.4 mm diameter hole produced by laser

beam.

The core tablet has 2 layers, one containingthe drug (the active layer) and the other

containing the polymeric osmotic agent (thepush 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 plasticmatrix e.g. Desoxyn

(methamphetamine HCl) tabs (Abbott);Procanbid (procainamide HCl tabs.(Parke-Davis)

Complex formation

Ion exchange resins


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K inet ics o f 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 availablefor release and therefore the rate of

release decl ines exponent ial ly w ith t ime.


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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 amountof drug remaining in the dosage form.

Therefore a constant amount of drug will be

released over time from extended releasedosage 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 releasefollowed by Osmotic controlled delivery devices?

Using a suitable graph, illustrate the profile thatwould 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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THANK YOU FOR YOUR ATTENTION

MODIFIED RELEASE

DOSAGE FORM

Download - Modified Release Dosage Form

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