Review Article

Nirav Soni, IJPRBS,

PRBS, 2012; Volume 1(5
1(5): 149-159

ISSN: 2277-8713
IJPRBS

TO PREPARE AN ORAL FORM OF GLICLAZIDE SR (SUSTAINDEDE RELEASE)RELEASE)

30 MG TABLET AND MANUFACTURING PROCESS DESCRIBING THE
FORMULATION AND PROCESS PARAMETERS.
Mr. Nirav Rajendra Kumar Soni
A-one
one pharmacy College, Anasan, Ahmedabad, Gujarat, India.
Abstract
Accepted Date:
Gliclazide contains not less than 99.0 per cent and not more

15/08/2012

than

Publish Date:

the

equivalent

of

101.0

per

cent

of

11

(hexahydrocyclopenta[c]pyrrol-2(1H)-yl)--3-[(4

27/10/2012

methylphenyl)sulphonyl]urea,
honyl]urea, The primary mechanism of
Keywords

action of gliclazide in lowering blood glucose appears to be

Field of the invention

dependent on stimulating the release of insulin from

Ingredients

functioning pancreatic beta cells. Gliclazide has been shown

Preformulation study

have extra pancreatic effects like reduction in platelet

Process parameter

adhesiveness and aggregation and increase in fibrinolytic

activity. Minimize dosing frequency, Minimizes fluctuations

Corresponding Author

in serum drug levels, for a drug having narrow therapeutic

Mr. Nirav R. Soni

index, to achieve zero order release rate of drug, Patients

A-one pharmacy College,

compliance.
ance. In preparation of Gliclazide having ingredients

Anasan, Ahmedabad,

CHPD, Mg-Sterate,
Sterate, Colloidal Silica, HPMC and Maltodextrin

Gujarat, India.

compatible with each other .In this preparation Gliclazide SR

- 30 mg having less cost effective and Intended for single
dose administration per day & better patient compliance
with sharping effect against diabetic condition.
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Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159

ISSN: 2277-8713
IJPRBS

INTRODUCTION

Ideally

drug

to

provide

desired

Gliclazide

is

second-generation

therapeutic action should arrive rapidly at

hypoglycemic sulfonylurea that is useful in

the site of action in optimum concentration,

the treatment of Type 2 diabetes mellitus.

remain there for the desire time, be

Gliclazide shows good tolerability and a low

excluded from other site and get rapidly

incidence of hypoglycemia; a low rate of

removed from the site of planned after its

secondary

action. The fact that absorption rate of drug

aggregation and increases fibrinolysis. Thus

into the body can be decreased by

gliclazide appears to be a drug of choice in

reduction of the rate of release of the drug

long-term sulfonylurea therapy for the

from the dosage form is one of the most

control of Type 2 diabetes mellitus. It shows

recent

low aqueous solubility and dissolution rate

and

interesting

result

of

failure

inhibits

platelet

pharmaceutical research. This ideal dosing

and

regimen,

patient

bioavailability after oral administration. The

against

enhancement of oral bioavailability of

overdosing and side effects, is made

poorly water-soluble drugs remains one of

possible by controlled release delivery

the most challenging aspects of formulation

systems, which use a variety of mechanisms

development. The solid dispersion of poorly

to deliver and maintain the drug at a certain

water-soluble

level in the patients blood stream1 This

polymers enhances drug dissolution and

ideal dosing regimen, which enhances

bioavailability.

patient compliance and helps guard against

characterization of complexes of gliclazide

overdosing and side effects, is made

with -cyclodextrin have been reported.

possible by controlled release delivery

Complexation

systems, which use a variety of mechanisms

cyclodextrinhydroxypropyl methylcellulose,

to deliver and maintain the drug at a certain

which enhanced its hypoglycemic activity,

level in the patients blood stream2.

has been reported. In addition, accelerated

compliance

which
and

enhances
helps

guard

often

shows

Available Online At www.ijprbs.com

low

drugs

The

of

in

and

irregular

water-soluble

preparation

gliclazide

with

and

Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159

ISSN: 2277-8713
IJPRBS

absorption of gliclazide using PEG 400 was

the drug is as well absorbed as the food

studied

of

stuffs that are ingested daily. In fact the

gliclazide in PEG 6000 have been developed

development of a pharmaceutical product

to

for oral delivery, irrespective of its physical

earlier.

increase

Solid

drug

dispersions

dissolution

rate.

Enhancement of the solubility of gliclazide

form

using polyvinylpyrrolidone K90 has been

optimization of dosage form characteristics

reported. The molecular weight of the

within the inherent constraints of GI

polymer may play a role in the performance

physiology.

of a solid dispersion. The rationale of the

understanding

present study was to investigate the use of

including GI physiology, pharmacokinetics,

lower molecular weight PEG 4000 for the

pharmacodynamics and formulation design

preparation of solid dispersions with the

are

objectives of improving dissolution. The

approach to the successful development of

solubility and dissolution rate of gliclazide

an oral pharmaceutical dosage form. The

can be enhanced in SDs with PEG 4000. The

more sophisticated a delivery system, the

solubilization effect of PEG 4000 rate of

greater is the complexity of these various

gliclazide and obtaining different behavior

disciplines involved in the design and

as compared with PEG 60003-6.

optimization of the system. In any case, the

involves

varying

Therefore

essential

of

extents

fundamental

various

to

achieve

of

disciplines,

systemic

scientific framework required for the

Sustained Release Drug Delivery System
Oral drug delivery has been known for
decades as the most widely utilized route of
administration among all the routes that

successful development of an oral drug

delivery

system

consists

of

basic

understanding of the following three

aspects;

have been explored for the systemic

delivery of drugs via various pharmaceutical
products of different dosage forms. The
reasons that the oral route achieved such

Physicochemical, pharmacokinetic and

pharmacodynamic characteristics of the
drug.

popularity may be in part attributed to its

The

anatomic

ease of administration as well as the

characteristics of the GIT.

traditional belief that by oral administration

Available Online At www.ijprbs.com

and

physiologic

Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159

ISSN: 2277-8713
IJPRBS

Physicochemical characteristics and the

inconsistent

drug delivery mode of the dosage form

Sustained

release,

to be designed.7

prolonged

action,

Oral ingestion has long been the most

convenient and commonly employed route
of drug delivery. Indeed, for sustainedrelease

systems,

the

oral

route

of

administration has by far received the most

attention with respect to research on

and

confusing

manner.

sustained

action,

controlled

release,

extended action, timed release, depot, and

repository dosage forms are terms used to
identify drug delivery systems that are
designed

to

achieve

prolonged

therapeutic effect by continuously releasing

medication over an extended period of time

physiological and drug constraints as well as

after administration of a single dose11

design and testing of products. This is

It is an anti-daiabetic containg drug involved

because there is more flexibility in dosage

sulphonylureas having class mentioned

form design for the oral route than there is

below:

for the parenteral route.8 The goal in

CATEGORY: It is a sulphonylureas

designing sustained or controlled-delivery

USE: Antidiabetic (in NIDDM-Non insulin

systems is to reduce the frequency of

dosing or to increase effectiveness of the
drug by localization at the site of action,
reducing the dose required, or providing
uniform drug delivery

The enormous

problems of patient compliance as well as

Dependent Diabetes mellitus )

HALF LIFE: 10.4 h (Duration of action is
10-24 h
BCS CLASS: class II
DOSE: 40-320 mg (in two divided dose)
30 & 60 mg(for MR)

the therapeutic desirability of controlled

tissue drug levels over the time course of
therapy are sufficiently compelling reasons
to warrant placement of drugs in a
sustained form of drug delivery

10

In the

past, many of the terms used to refer to

therapeutic systems of controlled and

Field of the invention

The present invention relates to matrix
tablet that enables the prolonged release of
gliclazide, the release being insensitive to
variation in the pH of the dissolution
medium, and that ensures regular and

sustained release have been used in an

Available Online At www.ijprbs.com

Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159

ISSN: 2277-8713
IJPRBS

continuous blood levels after absorption of

the total amount of gliclazide has been

the galenic form by ORAL ROUTE

release between 4 to 6 Hours after

administration moreover

By Matrix tablet invention

The controlled release is linear for a period

of more than 8 Hrs and is such that 50% of

The Matrix tablet according to the invention

tablet containing a dose of 30 mg gliclazide,

enables prolonged release of gliclazide that

and in blood levels of from 250 to 1000

results in Humans in blood levels of from

ng/ml after a daily administration of a

400 to 700 ng/ml 12 Hours at most after a

tablet containing a dose of 30 mg of

single administration by the oral route of a

gliclazide12-15.

MATERIALS

Ingredient

Role

Justification

Glicalazide

API (active pharmaceutical ingredient)

Anti-diabetic action

Calcium hydrogen Enables improved granule fluidity and In the final blend
phosphate

granule compressibility

dehydrate (CHPD)

Also slow down the dissolution kinetics.

Compatible with API,

To control the dissolution profile of the

Particle size needs control

active ingredient

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Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159
Magnesium

ISSN: 2277-8713
IJPRBS

Lubricant

In the final blend.

Sterate

Vegetable origin

(0.25-4%)

Compatible with API

Particle size needs control

Colloidal silica

Flow agent

Enhance flow property

Compatible with API

Hydroxyl
methyl

propyl Granulation purpose

Particle size needs control

cellulose To control dissolution profile

(HPMC)

. Compatible with API

Matrix

forming polymer
(5-20 % )
Maltodextrine

Enabling release of active ingredient that Granulation

(0.25- 3 %)

is perfectly prolonged and controlled

Compatible with API.

Carrier: PEG 6000

Preformulation Study
Solubility Enhancement of GLICLAZIDE16

Before: 40 % drug release/1 min

Method: Solvent Melting Method

After :100% drug release/1 min

Profile Component

Method

Criteria

Flow Property

Angle of repose: Inversly prop.

<30

Carrs index: inversly prop,

Hausner ratio,
Solubility
Melting point

In Water
1. Capillary melting

1-10mg/ml
-

2. Hot stage microscopy

3. DSC
Stability (With all excipients FTIR Spectroscopy ,DSC

Must be Compatible

to be used)
Assay

UV (227 nm)

95-105%

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Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159

ISSN: 2277-8713
IJPRBS

PROCESS & PARAMETER

Manufacturing process and Process parameter

Material Attributes and
Process Parameters

Density
Particle size
Particle shape
Particle charge
Proportion of
material
Nature of surface
Surface area
Chopper
Mixing time
Moisture content

Manufacturing process steps :

STEP : 1

Appearance

MIXING & GRANULATION

Dissolution

Mixture of gliclazide , maltodextrine

and calcium hydrogen phosphate
dehydrate ,followed by wetting of that
mixture with purified water ,The
resulting Wet mass is then Granulated ,
by RMG(Rapid Mixer Granulator )

- Kneading during Binder

addition

Quality Attributes to be
Considered

STEP :2

Assay
Content uniformity
LOD (Loss on Drying )

Blend uniformity

Granulated mass mixed with HPMC

- Kneading at slow Speed

after Binder addition
- Kneading at slow speed
STEP :3

-blender type and time

-RPM of blender

Lubrication

-yield of lubricated granule

mass

With colloidal and magnesium

stearate

-Pre-compression force
-Main compression
force
-Press speed
-Feeder speed/Type
-Ejection force
-Hopper design: Height
and ---- Vibration
-Hopper fill

STEP :4
Compression by rotary
compression machine

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Blend Uniformity
Particle Size
Distribution
Density
Flowability/Compr
-essibility

Assay
Content Uniformity
(whole and split)
Weight Variation
Hardness
Friability
Disintegration
Usable Yield

Review Article
Nirav Soni, IJPRBS,
PRBS, 2012; Volume 1(5
1(5): 149-159

ISSN: 2277-8713
IJPRBS

MANUFACURING PROCESS FLOW

In vitro Drug Release Study

Comparison

0.1N

Hydrochloric

followed by 6.8 Phosphate buffer

Volume: 900ml

Preparation

acid

Stability Study
Acelarated Stability study
Tablets stored for 3 months 40.2 oC and

Apparatus: USP-II (Basket)

RPM: 50 rpm

75.5% RH.
Carry out DSC for excipient compatibility

Temperature: 37C 0.5C

Time 24 hrs

Market

(Similarity study)

Dissolution parameter:
Medium:

with

Carry out in-vitro dissolution study and

compare it with before 3 months
m
results

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Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159

ISSN: 2277-8713
IJPRBS

QTPP
Quality Target Product Profile

Summary

It is marketed as Glizid, Glyloc and

Diamicron 30 mg MR (Available Products in

Reclide in India &

Diamicron in Canada. In the Philippines,

Regulated Marketed)

Servier markets it as Diamicron MR

Summary product characteristics emc

Many generic equivalents are also

(Electronic medicine compendium)

available e.g. Glubitor-OD, Clizid. It is

not marketed in the United States (US)

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Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159

ISSN: 2277-8713
IJPRBS

CONCLUSION

REFERENCES

For above preparation of GLICLAZIDE SR-30

1. Asgar A and Sharma SN: Evaluation of

mg is best compliance of patient and their

oral sustained release formulation. The East

related to reducing cost , after better

Pharm. 1991: 69-74.

Intended for single dose administration per

day Giving sharp effect against diabetic
condition. Solubility enhanced by PEG -6000
and/or Beta cyclodextrin. According to our
preparation having more effective to turn
against diabetes condition.

2. Haider SS, Monnujan N and Shahriyar

SM: Sustained release preparation of
metoclopramide hydrochloride based on
fatty matrix. Indian Drugs 2002; 39:73-9.
3. Reynolds JEF and Ed. Martindale: The
Extra

Pharmacopoeia

Available Online At www.ijprbs.com

XXX,

30th

ed.;

Review Article
Nirav Soni, IJPRBS, 2012; Volume 1(5): 149-159
Pharmaceutical Press:

London, 1993; pp

279280.

ISSN: 2277-8713
IJPRBS
11. Lachman L, Lieberman HA and Kanig JL:
The Theory and Practice of Industrial
Pharmacy. 3rd ed. Mumbai: Varghese

4. Dollery SC: Ed. Therapeutic Drugs;

Publishing House. 1987: 293-345.

Churchill Livingstone: London, 1991.

12. Vyas SP and Khar RK: Controlled Drug
5. Harrower AD: Comparison of efficacy,
secondary failure rate and complications of

Delivery: Concepts and Advances. 1st ed.

Delhi: Vallabh Prakashan. 2002.

sulfonylurea. J. Diabetes Complicat. 1994; 8:

201203.

13. Alderman DA: Swellable matrices as

systems for oral delivery. Int J Pharm. 1984;

6. Palmer KJ and Brogden RN: Gliclazide,

1-5.

an update of its pharmacological properties

and therapeutic efficacy in NIDDM. Drugs

14. Nigayale AG: Investigation of prolonged

1993; 46: 92125.

drug release from matrix formulation of

chitosan. Drug Dev Ind Pharm. 1990; 16:

7. Yie WC: Novel Drug Delivery Systems.

2nd Ed. New York: Marcel Dekker Inc; 1992

449-67.
15. Gomez AD: Role of water-uptake on

8. Robinson JR and Lee V: Controlled Drug

Delivery Fundamentals and Applications.
2nd Ed. New York: Marcel Dekker Inc: 373-

tablet disintegration: design of improved

method for penetration measurements,
Acta Helv. 1986; 61: 22-29.

374.
16. S Biswal: Enhancement of Dissolution
9. Banker GS and Rhodes CT: Modern
Pharmaceutics. 3rd Ed. New York: Marcel
DekkerInc. 1996; 575-609.
10. Gudsoorkar

VR

and

Rate of Gliclazide Using Solid Dispersions

with

Polyethylene

Glycol

PharmSciTech. 2008; 9 (2).

Rambhau

D:

Sustained release of drugs. The East Pharm.

1993; 36:17-22.

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6000

AAPS