Welcome to Scribd. Sign in or start your free trial to enjoy unlimited e-books, audiobooks & documents.Find out more
Download
Standard view
Full view
of .
Look up keyword
Like this
10Activity
0 of .
Results for:
No results containing your search query
P. 1
C-9 Modified Release

C-9 Modified Release

Ratings: (0)|Views: 458|Likes:
Published by Alyssa Uy
from Sir Nelson Tubon's lecture notes
from Sir Nelson Tubon's lecture notes

More info:

Published by: Alyssa Uy on Aug 27, 2010
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

08/23/2013

pdf

text

original

 
Page
1
of 
6
 
CHAPTER 9 - Solid Oral Modified-Release Dosage Form and Drug DeliverySystems
INTRODUCTION
 
Describes solid oral dosage forms and drug delivery system thatvirtue of formulation and product design have modified drugrelease features
 
Modified release
products provide either delayed release orextended release of drug
 
Most delayed release products
are enteric-coated tablets orcapsules designed to pass through the stomach unaltered, later torelease their medication within the intestinal tract
 
Enteric coatings
are used either to protect a substance fromdestruction by gastric fluids or to irritating drugs
Extended release products are designed to release their medication in acontrolled manner at a predetermined rate, duration, and location toachieve and maintain optimum therapeutic blood levels of drug
 
RATIONAL FOR EXTENDED RELEASE PHARMACEUTICALS
 
Extended release tablets & capsules
= take once or twice daily
Conventional forms
= 3 to 4 times daily to achieve sameTE
 
For non oral rate-controlled DDSs
= 24 hours for mosttransdermal patches to months to years
 – 
 
Ex.: Lovenorgestrel subdermal implants (NorplatSystem)
MULTIPLE DAILY DOSING
 
inconvenient for the patient and can result in missed doses,made-up doses, and noncompliance with the regimen
 
when doses are not administered on schedule, the resulting peaksand valleys reflect the optimum drug therapy
 
ADVANTAGES OF EXTENDED-RELEASE DOSAGE FORMS OVERCONVENTIONAL FORMS
 
Reduction in drug blood levels fluctuation
 
 –
controlling the rate of release eliminatedpeaks and valleys of blood levels
 
Frequency reduction in dosing
 
 –
extended-release products frequently deliver more than lessoften than conventional form DepoFoam Drug Delivery System
 
Enhanced convenience and compliance
 
 –
with less frequency in dosing, a patient is less apt to neglecttaking a dose, also it provides greater convenience with day andnight administration
 
 
Reduction in adverse side effects
 
 –
 
because of fewer blood level peaks outside therapeutic rangeand into toxic range, adverse side effects are less frequent
 
Reduction in overall health care costs
 
 –
overall cost of treatment may be less because of enhancedtherapeutic benefit, fewer side effects, and reduced time forhealth care personnel to dispense and administer drugs andmonitor patientsDISADVANTAGE OF ETENDED-RELEASE DOSAGE FORMS OVERCONVENTIONAL FORMS
 
loss of flexibility in adjusting the drug dose and/or dosageregimen
 
risk of sudden and total drug release
 
dose dumping due to failure in technology
TERMINOLOGY
 1.
 
Sustained Release (SR)
 –
Melatonex2.
 
Sustained Action (SA)
 –
Drixoral3.
 
Extended Release (ER)
 –
NOX34.
 
Long Acting (LA)
 –
Theraflu5.
 
Prolong Action (PA)
 –
 6.
 
Controlled Release (CR)
 –
Melatonin7.
 
Timed Release (TR)
 –
Vit-Min 100
 
Products bearing these descriptions differ in design andperformance and must be examined individually to ascertain theirrespective features
Rate-Controlled delivery
 
 
applied to certain types of drug delivery systems in which the rateof delivery is controlled by features of service rather than byphysiologic or environmental conditions like gastrointestinal pH ordrug transit time through the gastrointestinal tract
Modified release
 
 
has come into general use to describe dosage forms having drugrelease features based on time course and/or location that are
Uy, Alyssa V.2BPh
 
Page
2
of 
6
 
designed to accomplish therapeutic or convenience objectives notoffered by conventional or immediate-release forms
Extended-release
 
 
dosage forms of this type are the ones that allow a reduction indosing frequency form that necessitated by a conventional dosageforms, such as solution or an immediate-release drug dosage form
Delayed release
 
 
releases the drug at a time other than promptly afteradministration. The delay may be time base or base on theinfluence of environmental conditions such as gastrointestinal pH
Repeat action
 
 
two single doses of medication; one for immediate release;another one for modified release
Targeted release
 
 
drug release directed toward isolating or concentrating a drug in abody region, tissue or site of absorption or for drug action
Extended Release Oral Dosage Forms (Successful ER Product)
1.
 
Release from dosage forms at a predetermine rate2.
 
Dissolve in GT3.
 
Maintain sufficient Gastrointestinal residence time4.
 
Be absorbed at a rate that will replace the amount of drug beingmetabolized and excreted
CHARACTERISTICS OF EXTENDED-RELEASE PRODUCTS
1.
 
They exhibit very slow nor very fast rates of absorption and excretion
 
 
drugs with slow rates of absorption and excretion are usuallyinherently long-acting, and it is not necessary to prepare them inextended-release forms
 
drug with very short half-lives, less than 2 hours, are poorcandidates for extended release
 
drugs that act by affecting enzyme systems may be loner actingthan indicated by their quantitative half-lives because of theirresidual effects and recovery of the diminished biosystem2.
 
They are uniformly absorbed from the gastrointestinal tract
 
 
they must have good aqueous solubility and maintain adequateresidence time in the gastrointestinal tract
 
drugs absorbed poorly or at varying and unpredictable rates arenot good candidates for extended-release products
3.
 
They are administered in relatively small doses
 
 
drugs with large single doses frequently are not suitable forextended release because the tablet or capsule needed tomaintain a sustained therapeutic blood level of the drug would betoo large for the patient to swallow easily
4.
 
They possess a good margin of safety
 
 
the most widely used measure of the margin of a drug’s safety is
its therapeutic index, that is, the median toxic dose divided by themedian affective dose
 
the larger the therapeutic index, the safer the drug
 
drugs that are administered in very small doses or possess verynarrow therapeutic indices are poor candidates for formulationsbecause of technologic limitations of precise control over releaserates and the risk of dose dumping due to a product defect
5.
 
They are used in the treatment of chronic rather than acuteconditions
 
 
drugs for acute conditions require greater adjustment of thedosage by the physician than that provided by extended-releaseproducts
 
BASIS OF DRUG RELEASE
 
modifying drug dissolution bycontrolling excess of biologic fluids to the drug through the use of barrier coatings
 
controlling drug diffusion rate from dosage forms
 
chemical reaction or interaction between the drug substance orits pharmaceutical barrier and site-specific biologic fluids
BASIS OF DRUG RELEASE
 
modifying drug dissolution by controlling excess of biologic fluidsto the drug through the use of barrier coatings
 
controlling drug diffusion rate from dosage forms
 
chemical reaction or interaction between the drug substance orits pharmaceutical barrier and site-specific biologic fluids
 
C
OATED BEADS, GRANULES AND MICROSPHERES
 
using conventional pan coating or air suspension coating, asolution of the drug substance is placed on small intact nonparentseeds or beads made of sugar and stand or on microcrystallinecellulose sphere
Nonpareil seeds
 
 
425-
850μm
 
Microcrystalline cellulose
 
 
More durable during production than sugar-based cores
 
170-
600μm
Lipid materials used to coat granules
 
Beeswax
 
Carnauba wax
 
Glyceryl monostearate
 
Cetyl alcohol
 
Cellulosic material (ethyl cellulose)
 
Aqueous coating system eliminate the hazards and environmentalconcerns associated with organic based solvent systems
 
The thicker the coat, the more resistant to penetration and themore delayed will be the drug release and dissolution
 
Spansule
MULTITABLET SYSTEMS
 
small spheroidal compressed tablets 3 to 4 mm in diameter maybe prepared
 
each capsule contain 8 to 10 minitablets some uncoated forimmediate release and others coated for extended drug release
MICROENCAPSULATED DRUGMicroencapsulation
 
 
A process by which solid, liquid or even gases may be enclosed inmicroscopic particles by formation of thin coatings of wallmaterial around the substance
Gelatin
 
 
A common wall forming material and synthetic polymers, such aspolyvinyl alcohol, ethyl cellulose, polyvinyl chloride and othermaterials may be used
 
dissolving the wall material
 
encapsulated material is added to the mixture and the thoroughlystirred
 
Page
3
of 
6
 
 
a solution to second material is added, example of acacia
 
the final dry microcapsules are free-flowing discrete particles of coated material
 
wall material constitute into 20% of the total particle weigh
ADVANTAGE OF MICROENCAPSULATION
 
 
administered dose of a drug is subdivided into small units that arespread over a large area of the gastrointestinal tracts, which mayenhance absorption by diminishing local drug concentration (e.g.Micro-K ExtenCaps)
>Encapsulation.
All of the single and combination capsules areproduced here. The empty gelatin capsules are placed in hoppersand free-flowing to the machine. The bottom portion of thecapsule is filled, which is gravity-fed from a stainless steel bin into
the machine’s hopper. An average of 6 million capsules a day can
be produced.
EMBEDDING DRUG SLOWLY ERODING OR HYDROPHILIC MATRIX SYSTEM
 
drug substance is combined and made into granules with anexcipient material that slowly erodes in body fluids, progressivelyreleasing the drug for absorption
Hydrophilic cellulose polymers
 
 
commonly used as the excipient base in tablet matrix systems
EFFECTIVENESS OF THE HYDROPHILIC MATRIX IS BASED ON:
 
successive process of hydration on the polymer’s surface
 
 
gel formation on the polymer’s surface
 
 
tablet erosion
 
subsequent and continuous release of drug
Hydroxypropyl Methyl Cellulose (HPMC)
 
a free flowing powder; commonly used to provide the hydrophilicmatrix
 
A successful hydrophilic matrix system must contain thefollowing:
 
polymer must form a gelatinous layer rapidly enough to protectthe inner core of the tablet from disintegrating too rapidly afteringestion
 
20% of HPMC results in satisfactory rates of release for anextended-release tablet formation (e.g Oramorph SR Tablet)
Manufacturers may prepare two-layer tablets
 
 
one layer containing the uncombined drug for immediate release
 
the other layer having the drug encoded in a hydrophilic matrixfor extended release
they may also prepare a three-layer tablets
 
 
outer layers containing the drug for immediate release
 
some commercial tablets are prepared with an inner corecontaining the extended-release portion of the drug and an outershell containing drug for immediate release
EMBEDDING DRUG IN INERT PLASTIC MATRIX
 
Drug is granulated with an inert plastic material such aspolyethylene, polyvinyl acetate, o polymethacrylate and thegranulation is compressed into tablets
 
released from the inert plastic matrix by diffusion
 
retains its shape during leaching of he drug and during its passagethrough the alimentary tract
 
Example: Gradumet
COMPLEX FORMATION
 
 
form complexes that may be slowly soluble in body fluids,depending on the pH of the environment
 
slow dissolution rate (e.g. Rynatan)
 
salts of tannic acid, tannates, provide this quality in a variety of proprietary products
ION EXCHANGE RESINS
 
solution of a cationic drug may be passed through a columncontaining an ion exchange resin, forming a complex by thereplacement of hydrogen atoms
 
release of the drug depends on the pH and electrolyteconcentration in the gastrointestinal tract
 
release is greater in the acidity of the stomach than in the lessacidic environment of the small intestine
 
hydrocodone polistirex (Tussionex) and chlorpheniraminepolistirex suspension and phentermine resin capsules
Mechanism of ion exchange resins:
In the stomach
1. drug resinate + HCl ↔ acidic resin + drug hydrochloride
 
2. resin salt + HCl ↔ resin chloride + acidic drug
 In the intestine
1. drug resinate + NaCl ↔ sodium resinate + drug hydrochloride
 
2. resin salt + NaCl ↔ resin chlor
ide + sodium salt of drug
 
release is extended over 12 hours by ionic exchange
OSMOTIC PUMP
 
the pioneer oral osmotic pump drug delivery system is the Orossystem developed by Alza
 
composed of a core tablet surrounded by a semipermeablemembrane coating having a 0.4mm diameter hole produced bylaser beam. Example: Acutrim
 
core tablet has two layers, one containing the drug and the othercontaining a polymeric osmotic agent
Drug suspension orsolutionOsmotic drug coreDeliver orificesDelivery orificeWaterWaterRate controlling Polymeric osmoticSemipermeableOsmotic coremembranepush compartmentmembrane containing drug
A. Elementary OROS osmoticB. OROS Push-Pull Osmotic Systempump drug delivery system

Activity (10)

You've already reviewed this. Edit your review.
1 thousand reads
1 hundred reads
Zharyne Santos liked this
juksanthi2000 liked this
elizabeth_elizz liked this
randatag liked this
cyberlog212 liked this

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->