Metformin hydrochloride

By:-
G. TARUN
KUMAR REDDY B.pharm.,

INTRODUCTION:-
The drug delivery systems are those which control the rate of drug
delivery, sustaining the duration of therapeutic activity and targeting the drug to
the diseased tissue.
Thereby leading the better therapeutic effect with minimum side
effects. The different types of drug delivery systems are as follows:-

EXTENDED RELEASE TABLETS
The medical advances have been made in the area of drug
delivery with the development of novel dosage forms.
The area of sustained drug delivery has granted as the most
promising type of the drug delivery system.
The sustained release or extended release drug delivery
system can be solve problems concerning the targeting of a drug to a
specific organ or tissue.
The extended release tablets will provide controlling the rate
of drug delivery.

The terms used for extended release tablets are:-
EXTENDED
RELEASE
TABLETS
DELAYED
RELEASE
TABLETS
PROLONGED
RELEASE
TABLETS
SUSTAINED
RELEASE
TABLETS
CONTROLLED
RELEASE
TABLETS

ADVANTAGES:-
1. Enhance product saftey.
2. Improved Efficacy.
3. Improved patient compliance.
4. More accurate compared to other conventional drug
delivery systems.
DISADVANTAGES:-
1. Stabilty Problems.
2. Expensive.
3. May Alter With The Food.

PHYSICOCHEMICAL PROPERTIES:
IUPAC Name : N,N-Dimethyl imidodicarbonimidic diamide
DRUG PROFILE
Appearance White or almost white crystalline Powder
Solubility Soluble in water Freely soluble as HCl salt
Molecular formula C4H11N5
Molar mass 129.16 g mol−1
log P 1.254
State Solid
Melting point 223-226 oC
pKa 12.4
BCS CLASSIFICATION Class-III

LITERATURE REVIEW
• David P Figgitt et al., The purpose of this research was to formulate
and characterize solid dispersion (SD) of metformin hydrochloride using
methocel K100M as the carrier by the solvent evaporation and cog-
rinding method.
Characterization was performed by Fourier transform spectroscopy
(FTIR), ultraviolet,
The optimized formulation was subjected to accelerated stability
testing as per ICH guidelines.
• Basavaraj.k Nanjwade et al., To develop and characterize an oral
Prolonged-release matrix tablet of metformin hydrochloride using a
combination of a hydrophobic carrier and hydrophilic polymer and two
types of formulation techniques.

P. K. Bhoyar et al ., An attempt was made to sustain the release of
metformin HCl as well as to mask the bitter taste by complexation
technique using strong cation-exchange resins.
The drug loading into ion-exchange resin was optimized for mixing
time, activation, effect of pH, mode of mixing, ratio of drug:resin
and temperature.
The resinate was evaluated for micromeritic properties, taste
masking and characterized using IR. Using resinate sustained
release tablets were.

AIM
 Formulation and evaluation of prolonged release of Metformin
Hydrochloride Tablets.
OBJECTIVE
Under these considerations, objective of the work is
 To design the formula for Metformin Hcl ER tablets.
 To incorporate selected model drug candidates in the same formula and
prepare tablets.
 To evaluate the prepared tablets of Metformin hydrochloride.
 To study the in-vitro dissolution profile of prepared tablets.
 Stability evaluation studies were carried out.

PLAN OF WORK
Preformulation studies :-
*API characterization
*Organoleptic evaluation
*Solubility
*Analytical evaluation
*Bulk density
*Tapped density
*Angle of repose
*Compressibility index

Evaluation Of Tablets
Post Formulation Studies:-
Hardness
Uniformity of thickness
Friability
Weight variation
Content uniformity
In vitro dissolution Stability studies.

Extented release tablets containing 500 mg of model drug
were prepared with a total tablet weight of 750mg.
Considering the pre-formulation studies and the literature
survey conducted the excipients were selected and an
attempt to produce prolonged released tablets.

Add the lubricant (magnesium stearate)
COMPRESSS the blend for tablet formation
PASS THROUGH SIEVE (No:-40)
DIRECT COMPRESSION METHOD
METFORMIN BINDER(POVIDONE)+
ADD DILUENT

METHOD:
1. The powder blend is subjected to drying and was
compressed by direct compression method by using
Standard concave punches in 8 Station Kambet KMPC8
tablet punching machine
2. Punches of 17.5mm and 7mm diameter were used for
compression.
3. Tablet of 748mg and 753mg was prepared in different
trials by adjusting hardness and volume screw of
compression machine properly.

WET GRANULATION METHOD
Drug + polymer
Pass through sieve
No:- 40
Add Diluent , half part of binder Then Pass
through sieve(sieve No.40)
DM water
Prepare granules and lubricated it
with Magnesium sterate (pre-sifted
through sieve No. 60) mix 5 minutes
Subject the blend for
tablet formulation
(compression)

• METHOD:-
Compress with punches in 8 Station Kambet
KMPC8 tablet punching machine.
Standard concave punches of 17.5mm, with
breakline punches measuring the Tablet of
750mg,770mg,740mg and 760mg was prepared in
different trials by adjusting hardness and volume
screw of compression machine properly.

DEVELOPMENT OF METFORMIN OF PROLONGED
RELEASE TABLETS
Formula
INGREDIENTS Mg/Tab(T1)
API 500
Polyox-303 50
Lactose monohydrate 190
Mg Stearate 10
Total Weight 750

PRE-FORMULATION OF API
I. Pre Compression Parameters
1.Angle of Repose
The angle of repose has been used to characterize the flow
properties of solids.
This is the maximum angle possible between surface of pile of
powder or granules and the horizontal plane.
It was calculated using the following equation:-
Tanθ = h / r
θ = tan –1 h / r
Where, h = height of the powder heap
r = radius of the powder heap
θ= angle of repose

2.Bulk density:
Bulk density defined as the mass of many particles of the material
divided by the total volume they occupy.
The total volume includes particle volume, inter-particle void
volume, and internal pore volume.
Bulk density is not an intrinsic property of a material.
Bulk density = Weight of powder(g) / Bulk volume(ml)

3.Tapped density:-
Tapped densitiy of the drug was determined by pouring 25 gm
through a glass funnel into a 100 ml cylinder.
The cylinder was tapped from height of 2 inches until a constant
volume was obtained.
The volume occupied by the sample after tappings were recorded
and the tapped density was calculated by the formula below
Tapped density = Weight of powder(g) / Tapped volume(ml)

4.Carr’s compressibility index:-
Compressibility is the ability of powder to decrease in volume
under pressure.
It is one of the method to determine the flow properties by
comparing the bulk and tapped densities.
% Compressibility Flow description
<10 Excellent
11-15 Good
16-20 Fair
21-25 Passable
26-31 Poor
32-37 Very poor
>38 Extremely poor

Carr’s index of each formulation was calculated according to
equation given below:-
Tapped density – Bulk density
Tapped density
X 100Carr’s index =

II. Post- compression parameters:
The quantitative evaluation of a tablet’s chemical, physical and
bioavailability properties are important in the design of tablets and to
monitor product quality.
• General appearance:-
The general appearance of tablets, its visual identity is essential
for consumer acceptance, control of lot-to-lot uniformity and general
tablet-to-tablet uniformity.
The control of general appearance involves measurement
attributes such as
Tablet’s size
Shape
Color
Presence or absence of odour
Taste
Surface textures & etc.

• Hardness or crushing strength:-
The resistance of tablets to capping, abrasion or
breakage under conditions of storage, transportation and
handling before usage depends on its hardness.
It is measured either by Monsanto or Stokes hardness
tester, by applying pressure diametrally to the tablet.
Monsanto Hardness Tester

RESULT
IDENTIFICATION OF DRUG:
By UV Spectroscopy:
Determination of max of Anti hyperglycemic agent:
On the basis of preliminary identification test the drug scanned
and it was concluded that the drug had max of 232 nm
which was equal to max 232nm as reported (std.).
SPECTRUM POINT PICK METHOD

STABILITY STUDIES
 The stability studies were carried out by storing in HDPE containers under the
Accelerated stability conditions of 40ºC /70% RH for a period of 1 month.
 The tablets were evaluated for the parameters like weight variation, hardness,
friability, thickness, and percentage of drug content were evaluated for initial, 1st, 2nd,
3rd and 1month.
 The tablets displayed all parameters of optimized formulation F10 within specified
limits indicating the stability of the formulation.
Parameters 1st week 2nd week 3rd week 4th week
Weight variation (mg) 750±5 750±4 750±4 750±4
Thickness (mm) 5.75±0.6 5.75±0.7 5.75±0.7 5.74±0.6
Hardness (N) 180 ± 10 190 ± 10 185±10 180 ± 20
Friability (%) 0.045 0.15 0.15 0.015
Drug Content (%) 97 96 95 94
Stability Studies Of Metformin Prolonged Release Tablets

Stability Effect On In-Vitro Dissolution Of Optimized Formulation (F10) at 1,2,3&4 week.
Time (Hours)
% Drug Release
1st week 2nd week 3rd week 4th week
0 0 0 0 0
1 30 25 28 27
2 42 40 39 44
3 54 54 52 53
6 76 773 74 74
10 98 96 96 95
Stability Effect On In Vitro Drug release profile of Trial-10

BIBLIOGRAPHY
•United States pharmacopoeia (2008) Bulk density and tapped density,
Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-
232.
•Indian Pharmacopoeia (2012) Uniformity of weight of single dose
preparations, Friability, 2010, vol-1, page no: 140, 192-193.
•Lachman L. and Lieberman H.A., Pharmaceutical Dosage Forms, In;
Tablets, Vol. 2, Marcel Dekker, Inc., New York ,1989 pp.367-414
•Martin,A.; Physical pharmacy; Fourth edition ; PP 444-445.
•www.wikipedia.org/wiki/tablets
•www.pharmainfo.net/tablets/types-tablets
Remington The Science and Practice of Pharmacy, 21st edition Vol.-1,
Page No.1178-1198
•www.Drugbank.com

•Brahmankar D.M., Jaiswal S.B., “Biopharmaceutics &
Pharmacokinetics”; First Edition; p-335 (1995).
•Tripathi KD, Essential of medical pharmacology, 5th ed.New Delhi:
Jaypeebrothepublishing house;2003, 254-275.
•United States pharmacopoeia (2012) Bulk density and tapped
density, Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page
no: 231-232.
•Indian Pharmacopoeia (2012) Uniformity of weight of single dose
preparations, Friability, 2010, vol-1, page no: 140, 192-193.
•British Pharmacopoeia (2012) Angle of repose, vol-5, Appendix-
A465.

•http://www.researchwikis.com/Generics_Market_Analysis_Marketin
g_ Research.
•United States pharmacopoeia (2012) Bulk density and tapped density,
Carr’s index and Hausner’s ratio, USPNF 2008, vol-1, page no: 231-
232.

Metformin hydrochloride

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