You are on page 1of 35

CONTROLLED RELEASE ORAL

DRUG DELIVERY SYSTEM

Contents
Introduction
Advantages
Disadvantages
Types
References

Terminology:
Sustained Release Drug Delivery Systems:
Sustained release constitutes any dosage form that provides
medication over an extended time to maintain therapeutic blood or tissue
levels of the drug.

Controlled Release Drug Delivery Systems:


Controlled drug delivery is one which delivers the drug at a predetermined rate,

for locally or systemically, for a specified period of time.


Continuous oral delivery of drugs at predictable & reproducible kinetics for

predetermined period throughout the course of GIT.

Repeat-Action drug delivery systems:


Repeat-action tablets are an alternative method of sustained release in
which multiple doses of drug are contained within a dosage form, and each dose is
released at a periodic interval.

Delayed Release Drug Delivery Systems:


Delayed release systems may not be sustaining but these dosage forms
maintains the drug within the dosage form for some time before release.

Plasma concentration time


profile

WHY CONTROLLED RELEASE


Patient comfort and compliance
Therapeutic advantage
Reduction in adverse side effects and

improvement in

tolerability
Reduction in healthcare cost
Maximum utilization of drug enabling reduction in total
6

amount of dose administered

US Controlled Drug Delivery Market


Drug delivery market dominated by oral delivery systems
All Other Transdermal
8%
2%

Implant
10%

Oral CR
60%

Inhalation
27%

Source: IMS America - Drug delivery based products

Characteristics that should be


possessed by the Drug molecule
Dose less than 100mg
Low protein binding properties
Efficient GI absorption
Half life about 3-6hrs
Larger therapeutic index
Should not possess:
Half life less than 2hrs or greater than 8 hrs
High potency
Greater dose
8

Physicochemical Properties Of A Drug


Influencing Drug Product Design and
Performance:
Aqueous solubility:

Tetracycline dissolves to a greater extent in the stomach


than in the intestine, although it is best absorbed in the
intestine. Hence, poor candidates for controlled release
systems, unless the system is capable of retaining the drug in
the stomach and gradually releasing it to the small intestine or
unless the solubility is made higher and independent of the
external environment by encapsulating the drug with an acid.

Partition Coefficient and Molecular Size:

Drugs with extremely high partition coefficient (very oil


soluble) readily penetrate the membranes but are unable to
proceed further and vice versa with drugs with very low
partition coefficient (excessive aqueous solubility).

Protein Binding:

Many drugs bind to plasma proteins. Drug protein binding


can serve as depot for the drug producing a prolonged release
profiles, especially if a high degree of drug binding occurs.

Biological Factors Influencing Design and Performance of


Controlled Release Systems:
Absorption:
Aminoglycosides such as gentamycin and kanamycin.
Riboflavin is absorbed by an active transport process in the upper part of the GIT.

Distribution:
The distribution of drugs into tissues can be one important factor in the overall
drug elimination kinetics, since it not only lowers the concentration of circulating drug but
it also can be rate-limiting in its equilibration with blood and extracellular fluid.

Metabolism:
Hydralazine is metabolized by the intestinal wall and/or the liver during
absorption, although it is well absorbed.
In contrast, Bromocriptine is incompletely absorbed, the poor bioavailability of
which is further reduced by first pass metabolism in the liver resulting in an absolute
bioavailability of only 6%.

Role of Disease State:


Controlled release Aspirin tablets in the proper dosage provided
and maintained blood levels at therapeutic concentration over 8-10hrs, a duration
that was about twice as long as that provided by conventional tablets.

Role of Circadian Rhythm:


Several biological processes and disease states shown to be
influenced by circadian rythms. As a result, the response to certain drugs also
follows cicadian rythms.
Digitalis glycosides, antianginal, diuretics, Psychoactive drugs such
as amphetamines, Barbiturates, carbamazepine, ethyl alcohol and chlordiazepoxide .

Design principle of sustained release


dosage forms for release rate and
dose considerations:

Advantages
Total dose is low.
Reduced GI side effects.
Reduced dosing frequency.
Better patient acceptance and compliance.
Less fluctuation at plasma drug levels.
More uniform drug effect
Improved efficacy/safety ratio.
14

Disadvantages
Dose dumping.
Reduced potential for accurate dose adjustment.
Need of additional patient education.
Stability problem.

15

Types of Oral drug delivery System


1.Dissolution controlled Release Dosage Forms
2.Diffusion Controlled Release Dosage Forms
3.Combination of both dissolution & diffusion.
4.Osmotic pressure controlled system
5.Ion-Exchange Resins
6.pH Independent systems
7.Altered Density Formulations

16

Dissolution Definition:
Mass transfer from solid to liquid.
Rate determining step: Diffusion from solid to liquid.
Several theories to explain dissolution
Diffusion layer theory
Surface renewal theory
Limited solvation theory.

For Highly water soluble drugs

17

Matrix Type
Also called as Monolith dissolution controlled

system.

Soluble drug

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.

18

Slowly
dissolving
matrix

Encapsulation
Called as Coating dissolution controlled

system.

Soluble drug

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

19

Slowly
dissolving
or erodible
coat

Diffusion
Major process for absorption.
No energy required.
Drug molecules diffuse from a region of higher concentration to lower

concentration until equilibrium is attainded.


Directly proportional to the concentration gradient across the

membrane.

20

1) Matrix type Diffusion controlled


system
Drug is dispersed in insoluble matrix of
rigid non swell able hydrophobic
materials.
Like insoluble plastics (PVC, fatty
materials)

Popular for sustaining the release of highly


water soluble drugs
The materials for such matrices are generally
hydrophilic gum and may be of natural origin(
guar gum, tragacanth), semi synthetic
(HPMC, CMC, Xantham gum)or synthetic
(Polyarylamide)
-the drug and gum are granulated together
with
21 a solvent such as alcohol, and
compressed in to tablet

The release mechanism


the release of drug from the Swellable matrix

system initially dehydrated hydrogel involves continuous


absorption of water (resulting in hydration, gelling and
swelling of gum) and desorption of drug via a swelling
controlled diffusion mechanism. And forms Glassy hydrogel.

22

2)Reservoir type Diffusion controlled


system

These
systems
are
hallow
containing an inner core of drug
surrounded in a water insoluble
polymer membrane.
The polymer can be applied by
coating
or
microencapsulation
techniques .
Mechanism ....partitioning the drug
in
to
the
membrane
with
subsequent
release
in
to
surrounding fluid by diffusion.

Disadvantage..
Polymers .HPC,
ethyl
cellulose
Dose
dumping

polyvinyl acetate.
23

Dissolution & Diffusion Controlled


Release system
Drug encased in a partially soluble

membrane.

Pores are created due to dissolution

of parts of membrane.

It permits entry of aqueous medium

into core & drug dissolution.

Insoluble
membrane
Entry of
dissolution
fluid
Drug
diffusion

Diffusion of dissolved drug out of

system.

Ex- Ethyl cellulose & PVP mixture

dissolves in water & create pores of


insoluble ethyl cellulose membrane.

24

Pore created by
dissolution of
soluble fraction of
membrane

ION-EXCHANGE RESINS DRUG COMPL

Ion-exchange systems generally use resins composed of water-insoluble cross-linked


polymers.
These polymers contain salt-forming functional groups repeating positions on the
polymer chain.
The drug is bound to resin and released by exchanging with appropriately charged ions
in contact with the ion-exchange groups.
Resin+ - drug- + X- resin+ - X- + drug-

Resin- - drug+ + Y+ resin- - Y+ + drug+

TYPES OF RESINATES IN ORAL CDDS


1.SIMPLE RESINATES:
Suspended in Liquids, Filled in Capsules, Compressed into Tablets
2.MICROENCAPSULATED OR COATED RESINATES:
Better control over drug release because of rate controlling membrane like Ethyl cellulose,.
TECHNIQUES: Pan coating, Air Suspension, Interfacial Polymerization, Solvent Evaporation

3.PENNKINETIC SYSTEM:1.DRUG RESINATE IS PRETREATED


WITH PEG 400.
2.PRETREATED RESINATES ARE THEN COATED WITH ETHYL
CELLULOSE.

PH-INDEPENDENT SYSTEM FOR CONTROLLED RELEASE MATRIX TAB

Designed by incorporating release modifiers in the formu

ALTERED DENSITY SYSTEM:

A)LOW DENSITY SYSTEM/FLOATING


DOSAGE FORMS:
Bulk density<gastric fluids.

2.

Floating is achieved through

B)HIGH DENSITY SYSTEM:

1.Effervescent/gas generating
system:
gas generation increases size of DS
&decreases density.
Types: 1.conventional matrix tablets.
2.Layered matrix tablets.
3.core-coated tablets.
Prepared by:chitosan,NaHco3,citric
acid.

Non effervescent system:

a)Swelling/expanding system.
b)Inherently low density system

weight as retention
eg.Feo,Tio2,Baso4

C) Swelling /Expanding Systems:


Plug type systems
D)Muchoadhesive Systems:

Attached to mucin

Oral osmotic controlled dds

principle:osmotic pressure is required for release


of the drug at a constant zero order rate
OROS NEEDS FOUR BASIC COMPONENTS FOR THE DESIGN.
1.Rigid shape semi-permeable membrane surrounds the drug/ osmagent core.
2.A drug layer[ that also contain osmagent in a elementary osmotic pump design.]
3.Osmagent that imbibes water & generates osmotic pressure which drives the
dissolved drug through the orifice.
Osmagents: Nacl,Dextrose,Mannitol.
Swellable osmopolymers:HPMC,PEO.
4.Delivery orifice which is generally laser drilled into spm.

TYPES OF ORAL OSMOTIC SYSTEMS FOR


SOLID DRUG DELIVERY[TABLETS]
1.ELEMENTARY OSMOTIC PUMP

TYPES OF ORAL OSMOTIC SYSTEMS


3.BILAYER PUSH-PULL OSMOTIC
PUMP(PPOP)(Hydrodynamic pressure controlled)
in the form of two layer tablet.

a)Drug layer: diluents+low molecular wt


polymers+drug.

b)Push layer: HMW


osmopolymers(HPMC,PEO)

4.SANDWICHED OSMOTIC TABLET


SYSTEM(SOTS)
Comprises middle push layer&two
attached drug layers surrounded by spm
with two orifices.(MPL:swelling agent)

Recent Trends: OROS Technology


(ALZA corporation)
Single layer tablet: Drug

ELEMENTARY OSMOTIC PUMP

core (water soluble drug


with or without excipients)
Semipermeable membrane
with a drilled orifice
Water imbibition by the core
because of osmotic action
results in drug dissolution,
which is released at a
controlled rate through the
orifice
Not suitable for water insoluble drugs.
Examples: Sudafed 24
hours (Pseudoephedrine); Volmax (Salbutamol)
32

Recent trends: Geomatrix (SKY


Parma)
Products in market:
Cordicant -uno
Madopar DR
SULAR ER

This technology Controls amount,


timing and location of release in
body.
-Formulation with predictable and
reproducible drug release profile.
-Controls rate of drug diffusion
throughout release process,
ensuring 100% release Products
33

REFERENCES
Novel drug delivery system , volume 50,

Y.W.Chien
The theory & practice of industrial pharmacy,

Leon Lachman , Herbert A.Lieberman,


Joseph L.Kanig,3 rd edition.
The Eastern pharmacist, november 1993.

Sustained release drugs, V R.Gudsoorkar & D.Rambhau


page 27-32
Biopharmaceuitics & pharmacokinetics,

D M.Brahmankar & Sunil B. Jaiswal.


www.google.com
34

Thank you

35
NKV

Oral Controlled Drug Delivery System

You might also like