2. 2
The period between 1950 to 1970 is considered as period
of Sustained drug release
The main AIM of preparing sustained release formulation’s
was intended to modify and improve the drug performance
by
Increasing the duration of drug action
Decreasing the frequency of dosing
Decreasing the required dose employed
Providing uniform drug delivery
3. 3
The of SRDF’s is to obtain Zero order release from
the dosage form.
Zero order release is a release which is independent of
the amount of drug present in the dosage form.
Usually SRDF’s do not follow zero order release but
they try to mimic zero order release by releasing the
drug in a slow first order fashion.
Pharmacological action is seen as long as the drug is in
therapeutic range, problems occur when drug
concentration is above/below therapeutic range.
4. 4
Improved patient compliance:
Less frequent dosing
Allows whole day coverage.
Decreased local and systemic side effects.
Decreased GIT irritation.
Decreased local inflammation.
Better drug utilisation.
Decreased total amount of drug used.
Minimum drug accumulation on chronic dosing.
Improved efficiency in treatment.
Uniform blood and plasma concentration.
Decreased fluctuation in drug level i.e uniform pharmacological
response.
Increased bioavailability of some drugs
Special effects: SR Aspirin gives symptomatic relief in Arthritis after
waking
Economy
5. 5
DOSE DUMPING :Increase quantity of drug release causes dumping of
drug which in turn leads to toxicity.
REDUCED POTENTIAL FOR ACCURATE DOSE ADJUSTMENT:
Administrating a fraction of drug is not possible.
NEED FOR ADDITIONAL PATIENT EDUCATION:
“Do not Crush or Chew the dosage unit”.
“ Tablet residue may appear in stools”.
STABILITY PROBLEMS: The complexity of SRF’s will lead to stability
problem.
REDUCTION IN SYSTEMIC AVAILABILITY: Example Theophylline,
Procainamide and vitamin combinations.
6. 6
Retrieval of the drug is difficult in case of toxicity / poisoning /
hypersensitive reaction.
Higher cost of the formulation.
Half life: Drugs having shorter half life (less than one hour) and
drugs having longer half life (More than twelve hrs) cannot be
formulated as SRDF’s.
If a dosage form contains more than 500mgs., of active ingredient
formulation of SRDF’s is difficult.
If CRDF is required (With New polymers) cost of government
approval is very high.
7.
8.
9.
10.
11.
12.
13.
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Matrix Type
• Also called as Monolith dissolution
controlled system.
• Controlled dissolution by:
1.Altering porosity of tablet.
2.Decreasing its wettebility.
3.Dissolving at slower rate.
• First order drug release.
• Drug release determined by
dissolution rate of polymer.
• Examples: Dimetane extencaps,
Dimetapp extentabs.
Soluble drug
Slowly
dissolving
matrix
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Encapsulation
• Called as Coating dissolution
controlled system.
• Dissolution rate of coat depends
upon stability & thickness of
coating.
• Masks colour,odour,taste,minimising
GI irritation.
• One of the microencapsulation
method is used.
• Examples: Ornade spansules,
Chlortrimeton Repetabs
Soluble drug
Slowly
dissolving or
erodible coat
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Matrix Diffusion Types
• Rigid Matrix Diffusion
Materials used are insoluble plastics such as PVP & fatty
acids.
• Swellable Matrix Diffusion
1. Also called as Glassy hydrogels.Popular for sustaining
the release of highly water soluble drugs.
2. Materials used are hydrophilic gums.
Examples : Natural- Guar gum,Tragacanth.
Semisynthetic -HPMC,CMC,Xanthum gum.
Synthetic -Polyacrilamides.
Examples: Glucotrol XL, Procardia XL
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Higuchi Equation
Q = DE/T (2A.E Cs)Cs.t)1/2
Where ,
Q=amt of drug release per unit surface area at time t.
D=diffusion coefficient of drug in the release medium.
E=porosity of matrix.
Cs=solubility of drug in release medium.
T=tortuosity of matrix.
A=concentration of drug present in matrix per unit
volume.
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Reservoir System
• Also called as Laminated matrix device.
• Hollow system containing an inner core surrounded
in water insoluble membrane.
• Polymer can be applied by coating or micro
encapsulation.
• Rate controlling mechanism - partitioning into
membrane with subsequent release into surrounding
fluid by diffusion.
• Commonly used polymers - HPC, ethyl cellulose &
polyvinyl acetate.
• Examples: Nico-400, Nitro-Bid
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Reservoir System
Rate controlling
steps :
Polymeric content in
coating, thickness of
coating, hardness of
microcapsule.
25. 25
BASED ON DRUG MODIFICATION:
COMPLEX FORMATION
DRUG-ADSORBATE PREPARATION .
PRO DRUG SYNTHESIS.
ION EXCHANGE RESINS.
26. 26
Complex formation:
The rate of dissolution of solid complex in biological fluids and
rate of dissociation of complex in the solution are considered and they
depend upon pH and composition of gastric and intestinal fluids.
Drug-adsorbate preparation:
In this product is insoluble. Drug availability is determined by
rate of disabsorption.
Pro drug synthesis:
They are inactive and need enzymatic hydrolysis for
regeneration. Solubility, absorption rate of prodrug must be lower than
parent drug.
27. 27
Ion exchange resins:
They are water insoluble, cross linked polymers containing salt
forming groups. The drug is bound to the resin by using
chromatographic column or by prolonged contact.
Drug release from this complex depends on pH & property of
resin. Drug that is attached to the resin is released by exchanging
with the ions present in the GIT.
Resin+ -Drug- +X- Resin+- X- + Drug-
Example: Biphetamine.
28. 28
BASED ON DOSAGE FORM MODIFICATION.
Microencapsulation:
It’s a process in which tiny particles are surrounded by uniform
coating (microcapsule) or held in a matrix of polymer (microsphere.)
Spray drying is used which involves rapid evaporation of the solvent
from the drug surface.
Barrier coating:
In this one quarter of the granules are in non sustained form for
sudden drug release, remaining part are coated for sustained release.
Both these granules are filled in hard gelatin capsule or compressed in
a tablet, and the release mechanism is by diffusion. Coating material
used are fats, waxes.
29. 29
Matrix embedding: Drug is dispersed in a matrix of retardant
material which may be encapsulated or compressed in a tablet.
30. 30
Name Marketer Dosage form Indication
Carbotrol
Glucotrol Xl
Adderall XR
Procardia Xl
Ortho Evra
Dura gesic
Shri Us
Pfizer
Shri US
Pfizer
Ortho – Mcneil
Janssen
Oral capsule
Oral Tablet
Oral Capsule
Oral Tablet
Trans Dermal Patch
Trans Dermal Patch
Epilepsy
Hyperglycaemia
ADHD
Angina / Hypertension
Contraceptive
Chronic pain
