STAMFORD UNIVERSITY

BANGLADESH
Pharmaceutics - II
Assignment

Course Code: BPH - 320

Topic: Modified Release Drug Delivery System (MRDDS)

Submitted To:
Dr. Madhabi Lata
Assistant Professor
Pharmacy Department of
Stamford University, Bangladesh.

Submitted By:
Tabiku Sultana Orpa
ID: BPH-067 07411
SECTION: BPH – S - 67
Department of Pharmacy

Date of Submission: 03, May – 2021.

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Index

SL
No. Content Page No.

01 Definition of Modified Release Drug Delivery System 02

02 Examples of Modified Release Dosage Form 02 – 03

03 Prospect over other dosage form 03

04 Classification of Modified Release Dosage Form 03 – 04

05 Release pattern from the formulation of Modified Release Drug 04 – 05

06 Typical types of Modified Release Drug Delivery System 05

07 Advanced types of Modified Release Drug Delivery System 06

08 Challenges for formation of Modified Release Drug Delivery 06 – 07

System

09 List of MRDF/MR tablets available in Bangladesh 08 – 10

10 Method of Preparation of MRDF/MR Tablets available in 10 – 11

Bangladesh

11 Conclusion 11

12 Reference 12
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Definition of Modified Release Drug Delivery System

MRDDS is the abbreviation of Modified release drug delivery system.

The United States Pharmacopoeia definition of an MR (modified-release) system is that – “The

drug release characteristics of time, course and/or location are chosen to accomplish therapeutic
or convenience objectives not offered by conventional dosage forms.” This includes
technologies that modify the site of drug.

Modified-release products are widely used in the oral solid dosage form such as
tablet and capsule, they are the most preferred oral route of administration for
many drugs. The pharmaceutical manufacturers have formulated a variety of
dosage forms for patient compliance, with modified-release being one of them
that change the time or release rate of a medicament to match therapy goals in
disease management.

Examples of Modified Release Dosage Forms

Dosage forms that release drug in time and location dependent fashion. Provide convenience
and therapeutic objectives not offered by conventional or immediate release dosage forms.
Encompass dosage forms that do not release drug immediately after ingestion.

Examples,

Oral drug products – Transdermal drug delivery system –

1. Diltiazem HCL (extended release) 1. Clonidine (transdermal therapeutic
2. Diclofenac sodium (delayed release) system)
3. Ondansetron (oral soluble film)

Ophthalmic drug delivery – Intravaginal drug delivery –

1. Controlled release pilocarpine 1. Dinoprostone vaginal insert

Prospect over other dosage form

In addition to the modified form, there are two others which are very important in drug delivery
system. They are –
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Sustained-release dosage form &

Control release dosage form.
❖ Sustained-release dosage form
Sustained drug delivery may provide an immediate dose required for the normal
therapeutic response, followed by the gradual release of drug in amounts sufficient to
maintain the therapeutic response for a specific extended period of time usually 8 – 12
hours.
❖ Control release dosage form
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.

Classification of Modified Release Dosage form

There are four types of modified release dosage form

▪ Delayed release
▪ Extended release
▪ Repeat action
▪ Targeted action
▪ Prolonged-action dosage forms
▪ Repeat-action dosage forms
Extended One that allows a reduction in dosing frequency Examples –
release to that presented by conventional dosage form. Controlled release,
Designed to release their medication in controlled sustained release
manner, at pre-determined rate, duration and and long-acting
location in the body to achieve and maintain drug products.
optimum therapeutic blood levels of drug.

Delayed These are dosage forms designed to release the Examples – Enteric
release drug at a time other than promptly after coated dosage
administration. The delay may be time-based or forms like enteric
based on the influence of environmental coated aspirin, other
conditions such as Gl, pH, enzyme, pressure, etc. NSAIDS, etc.
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Repeat These are dosage forms usually containing 2 Example – Bi –

action single doses of medication, one for immediate and layered Tablets
the second for delayed release

Targeted Drug release that is directed towards isolating or

release concentrating a drug in a body region, tissue, or
site for absorption or drug action.

Prolonged- This type of dosage form has reduced the release

action rate of a drug from formulation after
dosage administration to keep therapeutic activity,
forms minimize toxic effects, or for any other
therapeutic purpose.

Repeat- A repeat action tablet usually contains two doses

action of the drug, the first one released immediately
dosage after oral administration, and the second dose is
forms released later when the layer of the enteric coating
dissolves.

Release pattern from the formulation of Modified release drug

There are two specific patterns available for modified release dosage form –

▪ Constant pattern
▪ Reducing pattern

Constant pattern Reducing pattern

Once the drug starts releasing the drug by Once the drug release starts by zero order
zero order kinetics, the concentration the kinetic, over the time, the concentration of
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plasma constant and remains above drug in plasma starts reducing but it remains
minimum effective concentration (MEC) but above MEC and below MIC.
below maximum toxic concentration (MTC)
for plasma drug concentration v/s time
profile. This will ensure prolonged duration
of drug therapy.

Typical Types of Modified Release Drug Delivery System

The typical types of modified release drug delivery systems are as follows –

❖ Matrix Controlled systems

The basic idea for matrix formulation is formation of mesh like structured throughout
the dosage form. The mesh structure will be the
deciding tactor for release rate of the drugs.
The matrix can be formed from hydrophilic
membrane, hydrophobic membrane or inert
plastic membrane. Since the matrix is present
throughout the dosage form, matrix
formulation can be crushed but not at all advised.
❖ Membrane Controlled Systems
The system is coated with polymeric membrane. The amount of coating used will be
the deciding factor for controlling the rate of release for the drugs. One more important
factor is the integrity of the polymeric membrane. It the membrane integrity is not
proper; the drug release can be rapid and may lead to dose dumping. The membrane
integrity can be studied by using Scanning Electron Microscopy. If the amount of
coating is applied in more quantity, the drug will not be able to release and may remain
stagnant in the membrane and leading to the undermedication. Hence, it is always
advised to use optimum concentration of
polymer coating tor particular dosage
form. The membrane coated dosage
form should not be crushed otherwise it
may cause sudden release of drug in the
blood plasma and leading to dose
dumping.
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❖ Osmotic Pump Delivery systems

This is less commonly used type of modified
release system. Here there is a presence to drug
reservoir surrounded by semipermeable osmotic
membrane. When the dosage form comes into
contact with water, drug gets solubilized and the solution exerts an osmotic pressure on
the semipermeable membrane. The orifice present on the semipermeable membrane
then releases the drug into blood stream.

Advanced Type of modified release drug delivery systems

There are four types of modified release drug delivery system in advanced. These are –

▪ Bilayer tablets
o Multiparticulate systems
▪ Nanotechnology
• Inserts/Bot system
▪ Hydrogels

We can know them briefly that is –

Bilayer tablets Consists of two layer – first layer releases the drug via immediate release
and second layer provides controlled release. This can aliso be used to
formulate dosage form containing two incompatible APls.
Multiarticulate The APls are coated with different concentrations of polymer for individual
systems particle of APl achieving different release pattern and improving the patient
compliance.
Nanotechnology This technology is on the boom. Liposomes, nanoparticles, SMEDS (Self
Micro Emulsifying Delivery Systems), SEDS (Self Emulsifying Delivery
Systems) are emerging drug delivery systems for achieving modified release
pattern.
Inserts/Bot Variety of machines containing API or use of nanobots containing API can
system be place at the target site and then machine will allow pulsatile drug delivery
systems.
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Hydrogels These are 3D crosslinked networks of water-soluble proteins. The degree of

crosslinking inside the hydrogel will control the release pattern tor the drug.

Challenges for formation of Modified Release Drug Delivery System –

• Drug solubility and permeability

Class IV drugs having low water solubility and low permeability drugs cannot be used
as modified release systems. it’s always advised to use solubility enhancers and
permeability enhancers in given dosage form.
• Concentration of polymer
When polymers are used tor forming membrane controlling devices, their concentration
will decide the release rate of drug into blood stream. Too much concentration or
polymer around the dosage form may not cause release of the drug since drug may
become stagnant in polymeric membrane.
• Integrity of the membrane
If the membrane integrity is not proper, there are chances of dose dumping Integrity of
depends upon the type of polymer used for the coating for optimum integrity and
concentration of polymer, it is always to advised to use the Design of experiment tool
to get productive results.
• IVIVC correlation
For any dosage form obtaining in vitro-in vivo correlations are major concern. The
same case is for modified release systems. One possible solution is to use simulated
models for obtaining in predicting the results.
• Therapeutic Index/Therapeutic window
Smaller the therapeutic index or therapeutic windows, potent is the concentration of
API. Any slight deviation for safety margins will lead to toxicity and slight deviation
from MEC will lead to undermedication. Hence the drugs having higher therapeutic
index are considered for modified release systems. ideal therapeutic index for APl
should be greater than 10 to form modified release systems.
• Dosage strength
Larger dosage strength should be avoided since increasing the dosage strength increases
the size of the dosage form and thus patient compliance 1s reduced.
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Though there are many challenges in forming modified release dosage forms but it is definitely
a better choice as part out novel systems for drug delivery.

List of MRDF/ MR Tablets available in Bangladesh

Drug Name Brand Company Dose & Indication Side effect

Name Name Therapeutic
Use
Admira MR UniMed
UniHealth
Consucon Incepta
MR Pharmaceutic
als Ltd.
Diamicron Servier
MR Bangladesh 30 mg & 60 Gliclazide is 1. Headache
Operation mg Tablet indicated for 2.
Diapro MR Beximco the treatment Gastrointestin
Pharmaceutic & of Non- al upsets,
als Ltd. insulin 3. Nausea
Diatrol MR Pacific Sulfonylureas dependent 4. Dizziness
1. Pharmaceutic diabetes 5. Skin
Gliclazide als Ltd. mellitus reactions
Dimerol Drug (NIDDM) of including
MR International patients who rash, Pruritus,
Ltd. requires oral erythema.
Glicid MR ACME antidiabetic
Laboratories treatment.
Ltd.
Glikazid Eskayef
MR Pharmaceutic
als Ltd.
Glimicron The White
MR Horse
Pharma
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Glix MR Navana
Pharmaceutic
als Ltd.
Glizid MR Opsonin
Pharma Ltd.
1. Glucozid Aristo
Gliclazide MR pharma Ltd.
Gored MR General
Pharmaceutic
als Ltd.
Kezid MR Kemiko
Pharmaceutic
als Ltd.
Angimet Orion
MR Pharma Ltd.
Anginox General
MR Pharmaceutic Tri-
als Ltd. metazidine
Angirid MR ACME Di-
Laboratories hydrochlorid 1. Dizziness
2. Tri- Ltd. e is 2. Headache
metazidine Angitrim Globe 35 mg Tablet indicated in 3. Abdominal
Di- MR Pharmaceutic adults as Pain
hydrochlo als Ltd. & add-on 4. Diarrhea
ride Angivas Popular therapy for 5. Dyspepsia
MR Pharmaceutic Other Anti- the 6. Nausea
als Ltd. anginal & symptomatic 7. Vomiting
Angivent Square Anti-ischemic treatment of 8. Rash
MR Pharmaceutic drugs. patients with 9. Pruritus
als Ltd. stable angina 10. Urticaria
Antoris MR Opsonin pectoris who 11. Asthenia
Pharmaceutic are
als Ltd. inadequately
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Cardimet Eskayef controlled

MR Pharmaceutic by or
als Ltd. intolerant to
Feelnor MR Incepta first-line
Pharmaceutic antianginal
als Ltd. therapies.
Metacard Aristo
MR pharma Ltd.
Metavas Nipro JMI
MR Pharma Ltd.

Method of Preparation of MRDF/MR Tablets available in Bangladesh

Preparation Method of Gliclazide

Method for preparing Gliclazide is disclosed, which comprises following steps: reacting p-
Toluene sulfonylurea as raw material with hydrazine hydrate to obtain compound by
condensation.

𝑁2 𝐻4 . 𝐻2 𝑂

Then the reacting compound with 1,2 -cyclopentane dicarboxylic anhydride to obtain
compound.

Finally, reducing compound II to obtain Gliclazide. The present method for preparing
Gliclazide avoids the use of amino heterocyclic group, and fundamentally solves the oxidation
trend of the raw materials. Intermediate compound II and its synthesis method are also
disclosed.
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Preparation Method of Trimetazidine Di-hydrochloride

2, 3, 4 -trimethoxy benzaldehyde was dissolved in of Formic acid and tetra butyl ammonium
bromide or para toluene sulphonic acid was added to it at room temperature. Piperazine was
also added to above reaction mass under stirring at room temperature.

Trimetazidine base was dissolved in isopropyl alcohol. Analytical grade Hydrochloric acid was
added to it.

But trimetazidine dihydrochloride synthesized by above method failed in single and total
impurity. The consent impurities are starting material impurity and process impurity. Hence
purification and re-purification is required which tend to loss of material resulting in low yield.

Trimetazidine base was dissolved in Isopropyl alcohol and water was added under
stirring. Analytical grade Hydrochloric acid was added to it and refluxed. Purity of the
compound was matched with standard trimetazidine dihydrochloride and found to be 99.98%

Conclusion

'Modified release' formulations are with the modification to have advantageous influence on
the escape/release of the drug from the dosage form in some way. Modified release drug
products have been successfully marketed for many years. The concept of Modified Release
Formulations emerged with an objective to improve patient’s compliance. Usually this is to
slow the release of the drug and keep steadier levels of the drug in the bloodstream so that the
medicine doesn't have to be taken too often and therefore improves compliance.
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Reference

Modified-Release Drug Delivery Technology Volume 2 by Michael J. Rathbone (Editor)

Jonathan Hadgraft (Editor) Michael S. Roberts (Editor) Majella E. Lane (Editor) (z-lib.org)

https://en.wikipedia.org/wiki/Modified-release_dosage

https://www.slideshare.net/mobile/DurgaBhavani60/modified-drug-delivery-systems-
targeted-drug-delivery-and-biopharmaceutical-drugs-pk-and-pd-drug-interactions

https://www.slideshare.net/mobile/SOMNATH34/modified-release-drug-products

https://www.slideshare.net/mobile/shiv3118/modified-release-drug-delivery-system

https://www.slideshare.net/shiv3118/modified-release-drug-delivery-system

https://www.slideshare.net/bknanjwade/fundamentals-of-modified-release-formulations

https://www.slideshare.net/bknanjwade/fundamentals-of-modified-release-formulations

https://accesspharmacy.mhmedical.com/content.aspx?bookid=513&sectionid=41488035

https://www.slideshare.net/shiv3118/modified-release-drug-delivery-system

https://www.contractpharma.com/csd/profile/recro-gainesville/view_modified-release-
dosage-forms-giving-new-life-to-drugs/

https://www.pharmtech.com/view/modified-release-formulations-improving-efficacy-and-
patient-compliance

https://www.sciencedirect.com/science/article/pii/B9780081000922000023