Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation method

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Scholar Research Library
Formulation and evaluation ofmetformin HCl micro beads by ionotropic
gelation method
Sagar Kishor Savale
Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education & Research, Karwand Naka,
Shirpur, - 425405. Dist: Dhule, Maharashtra State, India.
_____________________________________________________________________________________________
ABSTRACT
The Metformin HCL Micro Beads is formulated by the Ionotropic Gelation Method. The CMC is a Swellable
polymer is responsible for the Sustained release action or activity. A combination of CMC (Carboxy Methyl
Cellulose) and Sodium Alginate shows better sustained release activity. The PreparedSustained released Micro
Beadsis Evaluated In terms of bulk density, tapped density, angle of repose, Carr’s Index, Swelling Index, Drug
Content, % Encapsulation Efficiency and vitro study. The result associated in Optimized batch is good to
Satisfactory and having a good free flowing property. The Drug Content and % Encapsulation Efficiency values are
within the pharmacopeia limit. The in vitro Dissolution studies shows Maximum percentage of release of drug
(71.15) with in end of 4 Hours.
Keywords: Ionotropic Gelation, Micro beads, Sodium Alginate, Sustained released
_____________________________________________________________________________________________
INTRODUCTION
The Oral Route of administration is one of the specific route of administration having more patient acceptance or
convenience. The Metformin HCL Micro Beads is made by Ionotropic Gelation Method. The Metformin HCL
Micro beads is important for Maintaining the Stability of Vitamins and it is Important to Improve the Floability of
Vitamins. The beads are Encapsulated Material is used to reduce the Hygroscopicity of Nacl Solution. The Beads
are formulated with help of Carboxy Methyl Cellulose (CMC). The CMC is important for giving Sustained release
ation or activity. This are the Beads is release in prolonged action in extended Period of Time. The Metformin HCL
Micro Beads is Antihyperglycemic agent to reduce the blood sugar level and it is mainly used for the Type II
Diabetes Mellitus. [1-6]
MATERIALS AND METHODS
MATERIAL
Metformin HCL and all Formulation Excipient or Polymer [sodium Alginate, Calcium Chloride (cacl2), Carboxy
Methyl Cellulose (CMC)] was obtained from Pharmaceutics Laboratory of R. C. Patel Institute of Pharmaceutical
Education and Research, Shirpur 425405, Maharashtra State, one of the NBA and NAAC accredited and AICTE
approved institutes in India.
METHOD
The parameters of Authentication and Preformulation is carried out by pure drug Metformin HCLfor Maintaining
their Quality, Purity and Standard.

Sagar Kishor Savale Der Pharmacia Lettre, 2016, 8 (3):189-196
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190
AUTHENTICATION PARAMETERS
Melting Point Method
Melting Point determination is one of the preformulation property in which the temperature at which it changes state
from solid to liquid at atmospheric pressure. At the melting process the solid and liquid can exist equilibrium. The
Melting point of Metformin HCLpure drug is determine by using two types of method one is Conventional method
and another is Digital method.
Log P Value
Log p value is determined by using Partition Coefficient Phenomenon. In which The 1 gm of drug is added in
separating funnel containing equal portion of 25 ml of Octanol and 25 ml of Water. The separating funnel is shake
20 – 25 min. and stabilized the mixture. After stabilizing the mixture to remove water phase from separating funnel
and filter it. Take Absorbance of Filtrate and calculate the log p value (concentration of drug soluble in water phase
divided by concentration of drug soluble in organic phase)
Solubility Studies
The Term Solubility is defined as maximum amount of solute that can be dissolved in a given amount of solvent to
form a homogenous system at specified temperature and Specific Pressure to from Saturated Solution.
Procedure
To Prepare a different solutions Water, PH 1.2 Acidic Buffer, PH 6.8 Phosphate Buffer, PH 7.4 Phosphate
Buffer.
The drug material is added in to above solutions till Supersaturated Solution is from.
The Mixture can Placed in Orbital Shaker for 24 hrs. After 24 hrs. Filter the mixture Take Filtrate and Give
Absorbance.
To detect the Concentration of Drug is Soluble in Different Solutions.
Calibration Curve of Metformin HCL
Calibration Curve is determined by using UV Spectrophotometric methods. In which 10 mg drug is added in 100 ml
of water (100 µg/ml Solution). To Prepared different Dilutions (0, 2, 4, 6, 8, 10, 12) of above solution (100 µg/ml
Solution). Take Absorbance in respective λmax 240 nm.
PREFORMULATION STUDIES
Drug-Excipient Compatibility Studies
Drug is an active part of dosages form and it is mainly responsible for therapeutic value and Excipient substances
which are included along with drugs being formulated in a dosage form so as to impart specific qualities to them. It
is important for determination of Stability of the dosage forms. It’s also used for development of new drug delivery
system as well as investigation of new drug Product.
Procedure
The Equal portion of Drug and Excipient (1:1 ratio) is added in Ampules and the Ampules are placed in Stability
Chamber for one Weak, After One Weak the Drug Excipient Compatibility Study is Determine by using TLC (Thin
Layer Chromatography) (In TLC mobile phase is methanol: water: glacial acetic acid) , IR (Infrared Spectroscopy)
(In IR 1:9 ratio (drug : KBR))
METHOD OF FORMULATION
The Mucoadhesive Micro beads is Prepared by Ionotropic Gelation Method. The 1 gm of Carboxy Methyl Cellulose
(CMC) and 1 gm of sodium Alginate is added in 100 ml Water Containing Beaker. (Continuous Stirring is required
for addition of CMC and Sodium Alginate) The solution was put in Mechanical Stirrer for 30 min till formation of
clear solution and 200 mg Drug was added in this solution, the drug containing Solution Mix. Was under High
Pressure Homogenizer (HPH) for 20 min. till Homogeneous Solution is formed. In Another Beaker add 10 gm of
Calcium Chloride (cacl2) in 100 ml of Iso Propyl Alcohol (I.P.A.) (10 % Solution). By using Syringe with 24 needle
size, Take Solution of (Drug and CMC, Sodium Alginate) by using Needle 24 size and add drop to drop in Calcium
Chloride 10% Solution to from Spherical Micro beads. This Micro beads is Dried over Night in room Temperature.
After Drying Micro beads is formed and evaluated. All Formulation Ingredient is Reported in Table No. 1
EVALUTION PARAMETER [7-18]
Bulk density
It is a ratio of weight mass and Bulk Volume is known as Bulk Density. Amount of Powder is Weighed Separately
and transferred into 100 ml of measuring cylinder, initial volume of Powder Material is measured and calculated
bulk density according to following formula.

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191
Bulk density = Mass / Volume
Tapped Density
It is a Ratio of weight Mass and Tapped Volume is known as Tapped Density. Tapped density is Important
Evaluation Parameter is determined by placing a graduated cylinder containing a known mass of powder Undergoes
Tapping in Manually (100 Tapes) as well As Using a Mechanical apparatus under powder bed volume has reached a
minimum volume. The Tapped Density is calculated by following Formula.
Tapped density = Weight of Powder/ tapped volume of Powder
Compressibility Index or Carr’s Index
The Calculation of Compressibility index is based on the Tapped density and Bulk density. It is a ratio of Tapped
density and Bulk Density i.e. Compressibility Index.
Angle of Repose
It defines as the Pile surface of Powder is known as Angle of Repose. In this method of determination of angle of
repose in which the angle of repose is to pour the powder a conical on a level, flat surface and measure the included
angle. The Following Formula for determination of angle of repose.
θ -Tan -1
(h/r)
Where,
θ - Angle of repose,
h - Height of the powder cone,
r -Radius of the powder cone.
Swelling Index
The Equal weight of 100 mg Metformin HCL is Placed in Two Different Petri dish (one Petri dish contain Water
and another contain PH 1.2 Acidic Buffer) Kept aside for 1 hr. After one Hour take weight of Swelled Beads and
Calculate the Swelling Index of Metformin HCL Beads.
Swelling index was calculated using Following Formula:
Encapsulation Efficiency
The 100 mg of Metformin Micro Beads are added in 100 ml of water, the mixture was placed in orbital shaker for 24
hrs. After 24 hrs. Filter the solution and Take Filtrate of Solution and give Absorbance. Calculate the %
Encapsulation efficiency.
The following Formula for Determination of % Encapsulation efficiency:
Actual content of Drug / Theoretical Content of drug * 100
Drug Content
The 100 mg of Beads was crushed and add 100 ml of PH 1.2 Acidic Buffer to prepared 100 ppm Solution and Take
Absorbance by using UV Spectroscopy Technique at 240 nm.
The Drug Content is calculated by Following Formula:
Drug content:Actual drug content/Theoretical drug content * 100
Particle Size Distribution
The Particle size distribution is calculated in Motic Microscopy Method In which 100 mg of Beads was put in to
glass slide and add Menthe oil to formed Suspension. It is conducted in Motic Microscopy to conduct the Imaging of
Beads and Size Distribution was calculated.
In vitro drug release studies
Dissolution of Micro Beads is determined by Basket Type (USP I) of Dissolution Apparatus. The Beads was added
into cylindrical vessel containing 900 ml PH 1.2 Acidic media having 75 rpm for 4 hours and tem. 37±0.5˚C having
30, 60, 90, 120, 150, 180, 210, 240 Min. of interval. After every 30Min. 5 ml sample was Withdrawn and

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192
appropriate quantity of sample take absorbance by using U.V. spectroscopy technique and determine rate of
dissolution of Micro Beads.
RESULTS AND DISSCUSION
AUTHENTICATION PARAMETERS
Melting Point Method
The Melting Point of Metformin HCLis determined by Conventional and Digital Method and Melting Point of
Metformin HCLis Reported in Table No.2.
Log P Value
Log P Value is determined by Partition Coefficient Phenomenon and Log P Value of Metformin HCLis reported in
Table No.2.
Solubility Studies
The Solubility of Metformin HCLin Given Solution. (Water, PH 1.2 Acidic Buffer, PH 6.8 Phosphate Buffer, PH
7.4 Phosphate Buffer) is Reported in Table No.3.
Calibration Curve of Metformin HCL in water
The Calibration Curve of Metformin HCLis determined by using U.V. Spectroscopic Method. In which the
Absorbance of Metformin HCL in Different Concentration (0, 2, 4, 6, 8, 10, and 12) is reported in Table No.4. And
The Calibration Curve is shown in Figure No.1.
PREFORMULATION STUDIES
The Drug and Excipient Compatibility studies determined by TLC (Thin Layer Chromatography) and IR (Infrared
Spectroscopy) Method In which The TLC of Drug, Drug and Excipient before Stability Chamber and After Stability
Chamber is reported in Table No.5. And the IR of Pure drug Metformin HCL is shown in Figure No.2.
EVALUTION PARAMETERS
Bulk density
It is important parameter for determination of Flow characteristic in which the Bulk Density of Metformin HCL
Beads is reported in Table No.6.
Tapped Density
It is important parameter for determination of Flow characteristic in which the Tapped Density of Metformin HCL
Beads is reported in Table No.6.
Compressibility Index or Carr’s Index
The compressibility index is determined on the basis of Tapped density and bulk density and it is important for
determination of flow characteristic in which the Compressibility Index or Carr’s Index of Metformin HCL Beads is
reported in Table No.6.
Angle of Repose
It is important flow property for determination of flow of material and the value associated in angle of repose is less
than 40° is indicate good flow property in which angle of repose of Metformin HCL Beads tablet is reported in
Table No.6.
Swelling Index
The swelling Index of Metformin HCL Beads is reported in Table No.6.
Drug Content
The % Drug Content of Metformin HCL Beads Reported in Table No.6.
Particle Size Distribution
The Particle Size Distribution of Metformin HCL Beads by using Motic Microscopy and Particle Size Distribution
is reported in Table No.6.
In vitro drug release studies
The In vitro drug release studies of mucoadhesive Beads is determined in PH 1.2 Acidic Buffer, the absorbance of
Metformin HCL in PH 1.2 Acidic Buffer is reported in Table No.7. Calibration curve of Metformin HCL in PH 1.2

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193
Acidic Buffer shown in Figure No.3. The absorbance of concentration of Metformin HCL soluble in dissolution
medium in different time of interval and % CDR of Metformin HCL is reported in Table No.8. And the in vitro drug
released of Metformin HCL Beads is shown in Figure No.4.
Table No.1: Formulation Ingredients of Metformin HCL Beads
Sr. No. Ingredient F1 F2 FOP
1 Metformin HCL (Mg) 200 200 200
2 Sodium Alginate (gm) 0.85 0.95 1
3 Calcium Chloride (gm) 10 10 10
4 Carboxy Methyl Cellulose (CMC) (gm) 0.59 0.86 1
Table No.2: Melting Point and Log P Value of Metformin HCL
Sr.No. Parameters Result Std.
1 Melting Point (˚c) 223 - 227˚c 223 - 226˚c
2 Log p Value 0.5 0.5
Table No.3: Solubility of Metformin HCL in different solvents
Sr. No. Medium Concentration of drug Soluble (mg /ml)
1 Water 18.98
2 PH 1.2 Acidic Buffer 9.22
3 PH 6.8 Phosphate Buffer 5.27
4 PH 7.4 Phosphate Buffer 4.79
Result Class of drug BCS Class III
Table No.4: Calibration of Metformin HCL in Water
Concentration Absorbance
0 0
2 0.228
4 0.439
6 0.651
8 0.85
10 1.061
12 1.25
Table No.5: TLC of Drug and Drug: Excipient Before and after stability Chamber
Sr. No.
Samples
(Pure From of Drug material)
(Drug + Excipient Mixture)
Retention factor of drug
Before the Stability Chamber
Retention factor of drug
After the Stability Chamber
1 Pure Drug Metformin HCL 0.76 0.78
2 Metformin HCL + Sodium Alginate 0.79 0.77
3 Metformin HCL + Calcium Chloride 0.80 0.84
4 Metformin HCL + Carboxy Methyl Cellulose (CMC) 0.78 0.80
Table No.6: Evalution of Metformin HCL Beads
Sr.No. Parameters FOP Conclusion
1 Bulk Density (gm/cm3
) 0.62 Pass
2 Tapped Density (gm/cm3
) 0.74 Pass
3 Angle of Repose (θ) 20.12 Pass
4 Carr's Index (%) 19.35 Pass
5 Swelling Index (hrs.) 78 Pass
6 Particle Size Distribution (µm) 1162.18 ± 0.38 Pass
7 Encapsulation Efficiency (%) 79.69 Pass
8 Drug Content (%) 1.58 Pass
9 In Vitro Drug release (%) 71.15 Pass
Table No.7: The absorbance of Metformin HCL in PH 1.2 Acidic Buffer (In vitro drug release studies)
Concentration Absorbance
0 0
2 0.223
4 0.375
6 0.579
8 0.763
10 0.935

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194
Table No.8: % CDR of Metformin HCL Beds (Invitro drug release studies)
Time Abs Conc µg/ml DF Conc µg/ml Conc mg/ml Conc mg/5ml Conc mg/900ml CDR %CDR
0 0 0 0 0 0 0 0 0 0
30 0.086 0.765 10 7.650 0.0076 0.038 6.88 6.88 22.95
60 0.088 0.786 10 7.866 0.0078 0.0393 7.079 7.11 23.72
90 0.121 1.142 10 11.422 0.0114 0.0571 10.28 10.31 34.39
120 0.145 1.40 10 14.008 0.0140 0.070 12.607 12.66 42.21
150 0.161 1.57 10 15.732 0.015 0.078 14.15 14.22 47.43
180 0.189 1.87 10 18.75 0.0187 0.093 16.875 16.95 56.51
210 0.212 2.12 10 21.228 0.0212 0.1061 19.105 19.19 63.99
240 0.234 2.35 10 23.599 0.0235 0.1179 21.23 21.34 71.15
Figure No.1: Calibration curve of Metformin HCL in Water
Figure No.2:IR of Pure drug Metformin HCL
y = 0.0416x + 0.0155
R² = 0.9995
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 5 10 15 20 25 30 35
Absorbance
Concentration
Std. Calibration curve of Metformin HCL in Water

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195
Figure No.3: standard calibration curve of Metformin HCL in pH 1.2 Acidic Buffer
Figure No.4: In vitro drug released of Metformin HCL Beds
CONCLUSION
The Metformin HCL Micro Beads is formulated by the Ionotropic Gelation Method, The Beads are Stable in GI
tract (stomk and Intestine). The CMC is a Swellable polymer is responsible for the Sustained Release action or
activity. The Combination of Sodium alginate and CMC is responsible for prolonged released and sustained released
activity. The result associated in Optimized batch is good to Satisfactory and having a good free flowing property.
The Drug Content, % Encapsulation Efficiency and Swelling Index in these values are within the pharmacopeia
limit. The in vitro Dissolution studies shows Maximum percentage of release of drug.
Acknowledgement
The authors are grateful to Hon. Principal, SES’s,R. C. Patel Institute of Pharmaceutical Education and Research,
Dr. S. J. Surana sir. A special gratitude to Dr. H.S. Mahajan sirHead, Dept. of Pharmaceutics and Quality assurance.
Finally, we grateful to Dr. S.S. Chalikwar sir Assistant Professor, Department of Pharmaceutics and quality
assurance. Without whom and their constant caring and loving support we would be unable to achieve this
advancement and precious stage of our life.
y = 0.0928x + 0.015
R² = 0.998
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 2 4 6 8 10 12
Absorbance
Concentration
Standard calibration curve Metformin HCL in PH 1.2 Acidic
Buffer
y = 0.2701x + 7.8431
R² = 0.9697
0
10
20
30
40
50
60
70
80
0 50 100 150 200 250 300
%CDR
Time
In vitro release of Metformin HCL Beds

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196
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