The document discusses sustained release dosage forms. It begins by introducing drug delivery systems and how newer technologies have led to various techniques for delivering drugs. It then discusses the ideal properties of a drug delivery system, including maintaining therapeutic drug levels over an extended period of time and targeting the site of action. The document goes on to define and compare different types of modified release dosage forms such as sustained release, controlled release, and timed/delayed release forms. It provides details on the advantages and limitations of sustained release dosage forms.

1. SUSTAINED RELEASE
DOSAGE FORMS
Presented by:
Sujit R. Patel,
1st M. pharm.
DEPARTMENT OF PHARMACEUTICS,
Maratha Mandal’s College OF PHARMACY,
Belgaum - 590 010.
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2. INTRODUCTION
Drug delivery systems refer to the technology
utilized to present the drug to the desired body site
for drug release and absorption.
Newer discoveries and advancements in
technology has lead to various new techniques of
delivering the drugs for maximum patient
compliance at minimal dose and side effects.
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3. IDEAL DRUG DELIVERY SYSTEM
First, it should deliver drug at a rate dictated by the needs
of the body over the period of the treatment.
Second it should channel the active entity solely to the site
of action.
This is achieved by development of new various modified
drug release dosage forms, like-
 Control release dosage forms
 Time release dosage forms
 Sustained release dosage forms
 Site specific or targeted drug delivery systems etc
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4. SUSTAINED RELEASE DRUG DELIVERY: Any of the dosage form that
maintains the therapeutic blood or tissue levels of drug by continuous release
of medication for a prolonged period of time, after administration of a single
dose. In case of injectable dosage forms it may vary from days to months.
SITE SPECIFIC AND RECEPTOR TARGETING : Targeting a drug
directly to a certain biological location .For site specific release the target is
the adjacent to or in the diseased organ or tissue, for receptor release the
target is the particular drug receptor within an organ or tissue.
CONTROLLED RELEASE DRUG DELIVERY :Delivery of the drug at a
predetermined rate and /or to a location according to the needs of the body
and disease states for a definite period of time.
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5. Contd..
TIMED RELEASE OR DELAYED RELEASE: These are the
systems that use repetitive, intermittent dosing of a drug from one or
more immediate release units incorporated into a single dosage form or
an enteric delayed release systems e.g. Repeat action tablets and
capsules and enteric coated tablets where time release is achieved by
barrier coating, or wherein the release of the drug is intentionally
delayed until it reaches the intestinal environment.
REPEAT ACTION DOSAGE FORM: contain 2 or 3 full doses which
FORM
are so designed that the doses are released sequentially one after the other.
OTHER NOVEL(NEW) DOSAGE FORMS:
includes- Microspheres, Nanoparticles,, Trans-dermal delivery
systems, Ocular drug delivery, Nasal drug delivery, Implants etc.
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6. Sustained release
dosage forms
(SRDF’S)
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time 6

7. INTRODUCTION
Sustained release describes the release of
drug substance from a dosage form or
delivery system over an extended period of
time.
Also referred to as prolonged-release (PR),
slow release (SR), sustained action (SA),
prolonged action (PA) or extended-release
(ER).
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8. COMPARISION OF DRUG RELEASE
PROFILES
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9. Differences between sustained and
controlled drug delivery system
Sustained release Controlled release
dosage form dosage form
•Constitutes dosage form that •Constitutes dosage form that
provides medication over maintains constant drug levels in
extended period of time blood or tissue
•SRDF generally do not •Maintains constant drug levels in
attain zero order release the blood target tissue usually by
kinetics releasing the drug in a zero order
pattern.
•Usually do not contain
mechanisms to promote •Controlled dosage forms contain
localization of the drug at methods to promote localization
active site. of the drug at active site.
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10. Merits of SRDF
 Reduction in blood level fluctuations of drug, thus
better management of the disease.
 Reduction in dosing frequency.
 Enhanced patient convenience and compliance.
 Reduction in adverse effects(both systemic and local),
esp. of potent drugs, in sensitive patients.
 Reduction in health care costs.
 Improved efficiency of treatment.
 Reduces nursing and hospitalizing time.
 Maximum bioavailability with a minimum dose.
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11. Contd..
 Minimize drug accumulation with chronic dosing.
 Cure or control condition more promptly.
 Make use of special effects, e.g. Treatment of Arthritis.
 Constant blood levels achieve desired effect and this
effect is maintained for an intended period of time.
 Drug susceptible to enzymatic inactivation or by bacterial
decomposition can be protected by encapsulation in polymer
system suitable for SR.
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12. Limits of SRDF
 Administration of sustained release medication dose not
permit prompt termination of therapy. Immediate changes in
the drug if needed during therapy when significant adverse
effects are noted cannot be accommodated.
 The physician has less flexibility in adjusting dosage regimen,
as it is fixed by dosage form design.
 Sustained release dosage forms are designed for normal
population i.e. on basis of average biologic half-life.
Consequently, disease states that alter drug disposition,
significant patient variation, and so forth are not
accommodated.
 More costly process and equipment are involved in
manufacturing many sustained release dosage forms.
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13. Contd..
 Dose dumping
 Unpredictable and poor in vitro and in vivo relationship.
 Effective drug release time period is influenced and limited by GI
residence time.
 Need additional patient education.(such as not to chew or crush the
dosage form before swallowing)
 Drugs having very short half life or very long half life are poor
candidates for sustained release dosage forms. For Ex: diazepam.
 Delayed onset of action, hence sometimes not useful in acute
conditions
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14. Characteristics of Drugs
Unsuitable for Peroral SRDF
I. Those which are absorbed and excreted rapidly; short
biological half life(<1 hr). Ex- Penicillin G , Furosemide.
II. Those with long biologic half life(>12 hrs). Ex-
Diazepam, Phenytoin.
III. For those which require large doses(>1 gm)
Ex- Sulfonamides.
IV. Extensive binding of drugs to plasma proteins will have
long elimination half life and such drugs generally do not
require to be formulated to SRDF.
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15. Contd..
V. Those with cumulative action and undesirable
side effects. Ex-Phenobarbital
VI. Those with low therapeutic indices. ex-
Digitoxin.
VII. Those requiring precise dosage titration for
every individual. Ex- Warfarin, Digitoxin.
VIII. In general a very highly soluble drug or a highly
insoluble drug are undesirable for formulation
into SRDF product.
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16. Materials Used in Coating of Sustained
Release Dosage Forms (Encapsulation)
 Mixtures of waxes [bees wax, carnauba wax, etc] with glyceryl
monostearate , stearic acid , glyceryl mono palmitate and cetyl
alcohol.These provide coatings that are dissolved slowly or broken
down in the GIT.
 Shellac and zein – polymers that remain intact until the PH of the GI
contents become less acidic
 Ethyl cellulose , which provides a membrane around the dosage
form and remains intact throughout the GIT. However, it does
permit water to permeate the film, dissolve the drug , and diffuse out
again.
 Acrylic resins , which behave similarly to ethyl cellulose as a
diffusion controlled drug release coating material.
 Cellulose acetate [di acetate and tri acetate]
 Silicone elastomers.
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17. Polymers for Micro-encapsulation
Water-soluble resins
Water-insoluble resins
Waxes and lipids
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18. Water-soluble resins
Gelatin
Povidone (PVP)
CMC
HEC
MC
PVA
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19. Water-insoluble resins
Ethyl cellulose
Polyamide (Nylon)
Polyethylene
Cellulose nitrate
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20. Waxes and lipids
Paraffin
Carnauba
Beeswax
Stearic acid
Stearyl alcohol
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21. Physicochemical Properties of Drug
Candidate:–
Aqueous
Aqueous
solubility and pka
solubility and pka
Dose
Dose Partition
Partition
size
size coefficient
coefficient
Physicochemical
Physicochemical
properties
properties
Molecular size
Molecular size Drug
Drug
and diffusivity
and diffusivity stability
stability
Protein binding
Protein binding
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22. Physicochemical properties:–
1) Aqueous solubility & PKaː–
 Aqueous solubilityː–
A drug with good aqueous solubility,
especially if pH independent, serves as a
good candidates
Drug to be absorbed it first must dissolve in
the aqueous phase surrounding the site of
administration and then partition into
absorbing membrane.
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23. Contd..
Noyes Whitney Equation
dc = KDACs
dt
where ,dc/dt= dissolution rate.
KD = Dissoltion rate constant.
A = total surface area of drug.
Cs = aqueous saturation solubility.
Drugs with low aqueous solubility have low dissolution rate and have oral bioavailability problems.
E.g.: Tetracycline.
 Drugs with high aqueous solubility are undesirable to formulate SRDF’s.
E.g.: Paraacetamol
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24.  PKaː–
 The aqueous solubility of weak acids & weak
bases is governed by the pKa of the compound
and pH of the medium.
FOR WEAK ACID
St = So(1+Ka[H ] =So(1+10pH-pKa)
where, St – Total solubility of the weak acid
So – Solubility of the un-ionized form
Ka – Acid dissociation constant
H - Hydrogen ion concentration
Weakly acidic drug exist as unionized form in
the stomach absorption is favored by acidic
medium.
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25. FOR WEAK BASES
St = So(1+[H ] Ka) =So(1+pKa-pH)
Where, St – Total solubility of both
conjugate and free base form of weak base.
So– Solubility of the free base.
Weakly basic drug exists as ionized form in the
stomach hence absorption of this type is poor in
this medium .
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26. 2) Partition coefficientː –
Between the time a drug is administered and is
eliminated from the body, it must diffuse through
a variety of biological membranes.
• Oil/Water partition coefficient plays a major role
in evaluating the drug penetration.
K=Co/Cs
where, Co= Equilibrium concentration in organic phase.
Cs= Equilibrium concentration in aqueous phase.
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27.  According to ‘Hanch correlation’ a parabolic relationship
between the log of its partition coefficient has with that of the
log of its activity or ability to be absorbed.
activity
Log
Log K
 Drugs with extremely high partition coefficient are very
oil soluble and penetrates in to various membranes very
easily.
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28. Contd……..
There is an optimum partition coefficient for a drug in which it
permeates membrane effectively and shows greater activity.
Partition coefficient with higher or lower than the optimum are
poorer candidates for the formulation
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29. Contd……..
Values of partition coefficient below optimum result in the
decreased lipid solubility and remain localized in the first aqueous
phase it contacts.
Values larger than the optimum , result in poor aqueous
solubility but enhanced lipid solubility and the drug will not
partition out of the lipid membrane once it gets in.

30. 3) Drug stabilityː –
 Solid state undergoes degradation at much slower rate than
in the suspension or solution etc..
 Drugs stable in stomach gets released in stomach and which
are unstable gets released in intestine.
 Drugs with stability problems in any particular area of G.I.T
are less suitable for the formulation.
 Drugs may be protected from enzymatic degradation by
incorporation in to a polymeric matrix.
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31. 4) Protein bindingː –
 Drug binding to plasma proteins (albumins) & resulting retention of
the drug in the vascular space.
 Drug -protein complex can serve as a reservoir in vascular
space.
 Main forces for binding are Vander Waal forces, hydrogen
bonding , electrostatic forces.
 Charged compounds has greater tendency to bind proteins
than uncharged ones.
 Extensive binding of plasma proteins results in longer half-life
of elimination for the drug.
 E.x..95% binding in Amitriptyline , diazepam , diazepoxide.
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32. 5) Molecular size & diffusivityː –
The ability of a drug to diffuse through
membranes is called diffusivity which is a
function of molecular weight.
In most polymers it is possible to relate log
D to some function of molecular size as,
Log D = - Sv log v + Kv = - SM log M + Km
where,V – Molecular volume.
M – Molecular weight.
Sv, Sm, Kv & Km are constants.
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33. The value of D is related to the size and shape
of the cavities, as well as the drugs.
The drugs with high molecular weight show
very slow kinetics.
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34. 6) Dose sizeː –
 For those drugs requiring large conventional doses, the
volume of sustained dose may be too large to be practical.
 The compounds that require large dose are given in
multiple amounts or formulated into liquid systems.
 The greater the dose size,greater the fluctuation.
 So the dose should have proper size.
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35. Name Marketer Dosage form Indication
Carbotrol Shri Us Oral capsule Epilepsy
Glucotrol Xl Pfizer Oral Tablet Hyperglycaemia
Adderall XR Shri US Oral Capsule ADHD
Procardia Xl Pfizer Oral Tablet Angina / Hypertension
Ortho Evra Ortho – Mcneil Trans Dermal Patch Contraceptive
Dura gesic Janssen Trans Dermal Patch Chronic pain
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36. REFERENCEː–
1) Remington’s pharmaceutical sciences.
2) Sustained and controlled release systems.
-James W Robinson.
3) Theory and Practice of Industrial
Pharmacy.
-Lachmann and Liebermann.
4) Biopharmaceutics And Pharmacokinetics A
Treatise. - D.M. Brahmankar.
5) www.google.com
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