An overview about modified drug delivery,types and its technology.

1. A SEMINAR ON MODIFIED RELEASE DRUG DELIVERY SYSTEM
PRESENTED BY :
SHIV KUMAR
M.PHARM(PHARMACEUTICS)
DEPARTMENT OF PHARMACEUTICAL
SCIENCES AND TECHNOLOGY,MRSPTU

2. CONTENTS:
 INTRODUCTION
 TYPES OF MODIFIED RELEASE DOSAGE FORM
 DRUG CANDIDATE FOR ER PRODUCTS
 TECHNOLOGY FOR ER DRUG RELEASE
 EVALUATION OF MODIFIED RELEASE DOSAGE
FORM

3. INTRODUCTION
The term “modified release” refers to both delayed and
extended release systems for oral administration as well
as other delivery systems designed specifically to modify
the release of poorly water-soluble drugs.
Modified release dosage forms are drug delivery systems
(DDS) which, by virtue of formulation and product
design, provide drug release in a modified form distinct
from that of the conventional dosage forms. Drug
release can either be delayed or extended in nature.
Modified release dosage forms are those that alter the
timing and/or the rate of release of drug substance.

4. Examples of modified release dosage forms
Systems Examples of drugs
Oral drug products Diltiazem HCL (extended release)
Diclofenac sodium (delayed release)
Ondansetron (oral soluble film)
Transdermal drug delivery system Clonidine (transdermal therapeutic
system)
Opthalmic drug delivery Controlled release pilocarpine

5. TYPES OF MODIFIED RELEASE DOSAGE
FORM
A. Delayed release
B. Extended release
C. Repeat action
D. Targeted action

6. • EXTENDED RELEASE
One that allows a reduction in dosing frequency to that
presented by a conventional dosage form. Designed to release
their medication in controlled manner, at pre-determined rate,
duration and location in the body to achieve and maintain
optimum therapeutic blood levels of drug.
Examples-controlled release, sustained release and long
acting drug products.
• DELAYED RELEASE
These are dosage forms designed to release the drug at a time
other than promptly after administration.
The delay may be time-based or based on the influence of
environmental conditions such as GI, pH, enzyme, pressure, etc.
E.G – Enteric coated dosage forms like enteric coated aspirin,
other NSAIDS, etc.

7. • REPEAT ACTION
These are dosage forms usually containing 2 single
doses of medication, one for immediate and the
second for delayed release e.g. bi-layered tablets
• TARGETED RELEASE
Drug release that is directed towards isolating or
concentrating a drug in a body region, tissue, or site
for absorption or drug action

10. Drug-candidates for extended
release products
• They exhibit neither very slow nor very fast rates of absorption
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. Therapeutic Index
(TI)
• They are us ed in the treatmentof chronic rather than
acute conditions.

11. 1. ER Coated Granules or Microspheres –
• Granules of drug may be coated with lipid
materials such as beeswax, carnuba wax,
glycerylmonostearate, acetyl alcohol, etc.
• Careful blending of coated and un-coated granules
and with coatings of different thicknesses will
provide drug release of desired characteristics.
Examples: Toprol-XL (Metoprolol succinate) tabs.
(Astra);
Indocin SR (indomethacin capsules (Merck);
Technology of ER Dosage Forms

13. Technology of ER Dosage Forms
2.Embedding drug in slowly eroding or
hydrophilic matrix system –
The design comprises of the drug substance with excipient
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 tablets(Roxane)

14. 3.Multitablet system
• Small spheroid compressed tablets 3 to 4 mm in
diameter may be prepared to have varying drug
release characteristics.
• They may be placed in gelatin capsule shells to
provide the desired pattern of drug release.
• Each capsule may contain 8 to 10 minitablets, some
uncoated for immediate release and others coated
for extended drug release.

15. 4.Microencapsulated drug
MICROENCAPSULATION is a process by which very
tiny droplets or particles of liquid or solid material are
surrounded or coated with a continuous film of polymeric
material.
The product obtained by this process is called as
Microcapsules.

17. • The typical encapsulation process usually
begins with dissolving the wall material, say
gelatin, in water.
• The material to be encapsulated is added
and the two-phase mixture thoroughly
stirred.
• With the material to be encapsulated broken
up to the desired particle size,a solution of a
second material,usually acacia is added.

18. • This additive material concentrates the
gelatin into tiny liquid droplets.
• One of the advantages of microencapsulation
is that the administered dose of a drug is
subdivided into small units that are spread
over a large area of the gastrointestinal tract,
which may enhance absorption by diminishing
localized drug concentration.

19. 5.Osmotic pump
• OROS is the trademarked name owned by
ALZA Corporation,which pioneered the use
of osmotic pumps for oral drug delivery.
• The system is composed of a core tablet
surrounded by a semipermeable membrane
coating have a 0.4 mm diameter hole produced
by laser beam.

20. Osmotic core
containing drug
Osmotic delivery
orifice
Semipermeable
membrane
Osmotic pressure-controlled drug delivery system

21. • The system is designed such that only a few
drops of water are drawn into the tablet each
hour.
• The rate of inflow of water and the function of
the tablet depends upon the existence of an
osmotic gradient between the contents of the
bi-layer core and the fluid in the GI tract.
• Drug delivery is essentially constant as long
as the osmotic gradient remains constant.

22. The drug release rate may be altered by
of the
• Changing the surface area,
• The thickness or composition
membrane,
• Changing the diameter of the drug release
orifice.

23. SOME EXAMPLE OF OSMOTIC PUMP
SYSTEM
TRADE NAME MAUFACTURE GENERIC NAME
Acutrim Ciba Phenylpropanolamine
Covera-HS Searle verapamil
Dynacirc CR Sandoz Isradipine
Glucotrol XL Pfizer glipizide

24. 1. In vitro/In vivo correlations (IVIVCs)
IVIVCs is critical to the development of oral
extended-release products.
Assessing IVIVCs isimportant throughout the periods of
product development, clinical evaluation, submission ofan
application for FDA- approval for marketing, and during
post-approval for any formulation manufacturing changes.
Three categories of IVIVCs are included in the document:
• LEVEL A
• LEVEL B
• LEVEL C
EVALUATION OF MODIFIED-RELEASE DRUG
PRODUCTS

25. Level A
A predictive mathematical model for the relationship
between the entire in vitro dissolution/release time
course, e.g., the time course of plasma drug
concentration or amount of drug absorbed.
Level B
A predictive mathematical model of the relationship
between summary parameters that characterize the in
vitro and in vivo, time courses.
Level C
A predictive mathematical model of the relationship
between the amount dissolved in vitro at a particular time
(or T50%) and a summary parameter that characterizes
the in vivo time course (e.g. Cmax or AUC).

26. 2.DISSOLUTION STUDIES
• Reproducibility of the method
• Proper choice of the medium
• Maintainence of sink condition
• Dissolution rate as function of pH, ranging
from 1-8

27. 3.EVALUATION OF IN-VIVO BIOAVAILABILITY DATA
1. PHARMACOKINETIC PROFILE
Plasma drug conc.-time curve should adequately
define bioavailabilty of drug from dosage form.
The bioavailability data should demonstrate the
extended release characteristics of the dosage
form compared to reference/immediate release
product.

28. 2. RATE OF DRUG ABSORPTION
• For a extended release drug product to claim
zero-order absorption.
3. OCCUPANCY TIME
• The time required to obtain plasma drug levels
within therapeutic window is known as
occupancy time.
• For drugs whose therapeutic window are known,
plasma drug conc. can be maintained above the
minimum effective drug concentration.

29. REFERENCE
• Shargel leon, WU Pong Susanna, B.C. YU Andrew,
Applied Biopharmaceutics and Pharmacokinetics,5th
edition,rights by McGraw-hill, page no.-516-551.
• http://accesspharmacy.mhmedical.com/content.aspx
?bookid=513&sectionid=41488035
• https://en.wikipedia.org/wiki/Modifiedrelease_dosage
• https://www.slideshare.net/arijabuhaniyeh/modified
drug-release-pharmaceutics
• http://gpublication.com/index.php/crbps/article/
download/476/186

30. THANK YOU