The metformin is anti diabetic drug. In this study the sodium alginate beads were prepared with different oils preparing emulsion first. The drug is entrapped and measured for its drug content and swelling index. The beads were prepared and evaluated on different parameters.&nbsp

Chopra, Hitesh

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To Chemistry Journal Vol 2 (2019) ISSN: 2581-7507                                  http://purkh.com/index.php/tochem 
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Development and Characterization of Sodium Alginate Beads for Metformin 
Megha, Satvir Singh1, Hitesh Chopra*2 
1 Asbasjsm Cop Bela, Ropar-140001 
2 Chitkara College Of Pharmacy, Rajpura 
chopraontheride@gmail.com 
1. Introduction 
1.1. Hydro Gel 
The materials of interest are primarily hydrogels, which are polymer networks extensively swollen with water. 
Hydrophilic gels that are usually referred to as hydrogels are networks of polymer chains that are sometimes 
found as colloidal gels in which water is the dispersion medium 
Researchers, over the years, have defined hydrogels in many different ways. The most common of these is that 
hydrogel is a water-swollen, and cross-linked polymeric network produced by the simple reaction of one or 
more monomers. Another definition is that it is a polymeric material that exhibits the ability to swell and retain 
a significant fraction of water within its structure, but will not dissolve in water. Hydrogels have received 
considerable attention in the past 50 years, due to their exceptional promise in wide range of applications. They 
possess also a degree of flexibility very similar to natural tissue due to their large water content. 
The ability of hydrogels to absorb water arises from hydrophilic functional groups attached to the polymeric 
backbone, while their resistance to dissolution arises from cross-links between network chains. Many materials, 
both naturally occurring and synthetic, fit the definition of hydrogels. 
During last two decades, natural Hydrogels were gradually replaced by synthetic hydrogels which had long 
service life, high capacity of water absorption, and high gel strength. Fortunately, synthetic polymers usually 
have well-defined structures that can be modified to yield tailor able degradability and functionality. Hydrogels 
can be synthesized from purely synthetic components. Also, it is stable in the conditions of sharp and strong 
fluctuations of temperatures. 
Recently, hydrogels have been defined as two- or multi-component systems consisting of a three-dimensional 
network of polymer chains and water that fills the space between macromolecules. Depending on the properties 
of the polymer (polymers) used, as well as on the nature and density of the network joints, such structures in an 
equilibrium can contain various amounts of water; typically, in the swollen state, the mass fraction of water in a 
hydrogel is much higher than the mass fraction of polymer. In practice, to achieve high degrees of swelling, it is 
common to use synthetic polymers that are water-soluble when in non-cross-linked form. 
Hydrogels may be synthesized in a number of “classical” chemical ways. These include one-step procedures like 
polymerization and parallel cross-linking of multifunctional monomers, as well as multiple step procedures 
involving synthesis of polymer molecules having reactive groups and their subsequent cross-linking, possibly 
also by reacting polymers with suitable cross-linking agents. The polymer engineer can design and synthesize 
polymer networks with molecular-scale control over structure such as cross-linking density and with tailored 
properties, such as biodegradation, mechanical strength, and chemical and biological response to stimuli [1, 2]. 
To Chemistry Journal Vol 2 (2019) ISSN: 2581-7507                                  http://purkh.com/index.php/tochem 
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1.2. Classification of Hydrogel 
 
1.3. Metformin 
Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus 
(NIDDM). It improves glycemic control by decreasing hepatic glucose production, as well as decreasing glucose 
absorption and increasing insulin-mediated glucose uptake. 
Another well-known benefit of this drug is modest weight loss. Metformin is the drug of choice for obese NIDDM 
(non-insulin dependent diabetes mellitus) patients. Metformin was approved in Canada initially in 1972, the 
1970s in Europe, and in 1995 in the USA [3]. 
a. Structure                
 
 
To Chemistry Journal Vol 2 (2019) ISSN: 2581-7507                                  http://purkh.com/index.php/tochem 
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b. Pharmacology 
Indication: for use as an adjunct to diet and exercise in adult patients with non-insulin dependent diabetes 
mellitus. Metformin may also be used for the management of metabolic and reproductive abnormalities 
associated with polycystic ovary syndrome (PCOS). Metformin may be used concomitantly with a suifonylurea 
or insulin to improve glycemic control in adults. 
c. Pharmacodynamics 
Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves 
insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does 
not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause 
hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and 
day-long plasma insulin response may actually decrease. 
d. Mechanism of Action 
Metformin's mechanism of action is unique from other classes of oral antihyperglycemic drugs. Metformin 
decreases blood glucose levels by decreasing hepatic glucose production (gluconeogenesis), decreasing the 
intestinal absorption of glucose, and increasing insulin sensitivity by increasing peripheral glucose uptake and 
utilization. It is well established that metformin inhibits mitochondrial complex I activity, and it has since been 
generally postulated that its potent antidiabetic effects occur through this mechanism. 
Findings of recent studies however, show that metformin, at clinically relevant plasma concentrations, inhibits 
hepatic gluconeogenesis in a redox-dependent manner independently of reduction in citrate synthase flux, liver 
nucleotide concentrations, acetyl-CoA carboxylase enzyme activity, or gluconeogenic enzyme protein 
expression. Studies show that clinically relevant concentrations of plasma metformin attained by acute 
intravenous, acute intraportal or chronic oral administration in awake healthy and diabetic rats inhibit 
gluconeogenesis from lactate and glycerol, but not from pyruvate and alanine, implying an increased cytosolic 
redox state in mediating metformin's glucose-lowering effects. These effects have occurred independently of 
complex I inhibition demonstrated by unaltered hepatic energy charge and citrate synthase flux. Normalizing 
the cytosolic redox state by infusion of methylene blue or substrates contributing to gluconeogenesis 
independently of the cytosolic redox state stopped metformin-mediated inhibition of gluconeogenesis in vivo. 
In mice expressing constitutively active acetyl-CoA carboxylase, metformin acutely reduced hepatic glucose 
production and increased the hepatic cytosolic redox state without altering hepatic triglyceride content or 
gluconeogenic enzyme expression. 
Previous studies indicate that the glucose-lowering effects of metformin are mediated by the activation by 
metformin of AMP-activated protein kinase (AMPK), a liver enzyme which plays an important role in insulin 
signalling, energy balance, and the metabolism of both glucose and lipids. The activation of AMPK is thought 
to be necessary for metformin's inhibitory effect on the production of glucose by liver cells. Increased peripheral 
utilization of glucose may be due to improved insulin binding to insulin receptors. Metformin administration 
also increases AMPK activity in skeletal muscle. AMPK is known to trigger GLUT4 transporter deployment to the 
plasma membrane, resulting in insulin-independent glucose uptake [4]. 
e. Absorption 
The absolute bioavailability of a metformin 500 mg tablet administered under fasting conditions is 
approximately 50% to 60%. Studies using single oral doses of metformin 500 to 1500 mg, and 850 to 2550 mg, 
show that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption 
rather than an alteration in elimination. Food decreases the extent of and delays the absorption of metformin, 
as shown by approximately a 40% lower mean peak plasma concentration (Cmax), a 25% lower area under the 
plasma concentration versus time curve (AUC), and a 35-minute prolongation of time to peak plasma 
To Chemistry Journal Vol 2 (2019) ISSN: 2581-7507                                  http://purkh.com/index.php/tochem 
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concentration (Tmax) after administration of a single 850 mg tablet of metformin with food, compared to the 
same dose administered fasting. The clinical relevance of these decreases is unknown [5]. 
f. Volume of Distribution 
654 L for metformin 850 mg administered as a single dose. The volume of distribution following IV 
administration is 63-276 L, likely due to less binding in the GI tract and/or different methods used to determine 
volume of distribution. 
g. Protein Binding 
Metformin is negligibly bound to plasma proteins, in contrast to sulfonylureas, which are more than 90% protein 
bound. 
h. Metabolism 
Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the 
urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary 
excretion. 
Half Life 
Approximately 6.2 hours in the plasma and in blood, the elimination half-life is approximately 17.6 hours, 
suggesting that the erythrocyte mass may be a compartment of distribution. 
Clearance 
Renal clearance is about 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the 
major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug 
is eliminated via the renal route within the first 24 hours [6]. 
i. Toxicity 
Acute oral toxicity (LD50): 350 mg/kg in the rabbit. 
j. Common Adverse Effects 
The most common adverse effects of metformin include: epigastric discomfort, nausea, flatulence, and vomiting. 
Diarrhoea, drowsiness, weakness, dizziness, malaise, and headache may also occur [7]. 
2. Experimental Work 
The beads containing Metformin hydrochloride were prepared by using emulsion-gelation method. Required 
amount of sodium alginate was dissolved in 20 ml distilled water with constant stirring. Add different variety of 
oil then add accurately weighed quantity of Metformin HCl to sodium alginate solution. The final mixture 
containing sodium alginate was stirred at 400 rpm continuously for 15 min until the homogenous and stable 
suspension remained formed. Then the suspension is drop by drop 22 G needle into 5% (w/v) calcium chloride 
solution (100ml) [8,9]. 
 
 
To Chemistry Journal Vol 2 (2019) ISSN: 2581-7507                                  http://purkh.com/index.php/tochem 
179 
 
Formulation 
 
 
Metformin(mg) 
Sodium 
Alginate 
(mg) 
Calcium 
Chloride 
(5%w/v) 
(ml) 
 
RPM 
 
Oil(2.5ml) 
F1 500 1000 100 400 Castor oil 
F2 500 1000 100 400 No oil 
F3 500 1000 100 400 Liquid 
paraffin 
 
 
Diagramatic representation for preparation of sodium alginate beads 
3. Evaluation Parameters 
Percentage yield:  The percentage of production yield was calculated from the weight of dried microspheres 
recovered from each batch and the sum of initial weight of starting materials. The percentage yield was 
calculated using the following formula [10] 
Percentage yield = (practical yield/theoretical yield) *100 
To Chemistry Journal Vol 2 (2019) ISSN: 2581-7507                                  http://purkh.com/index.php/tochem 
180 
Drug entrapment efficiency: Accurately weighed 50mg of prepared beads from each batch were taken 
separately and were crushed using pestle mortar. The crushed powder was placed in 50ml of phosphate 
buffer7.4 and kept for 24h with occasionally shaking. After the stipulated time, the mixture was stirred at 200rpm 
for 30min on a magnetic stirrer. The polymer debris formed after disintegration of beads was removed by 
filtering through Whatman filter paper. After that drug content in the filtrate samples were determined using a 
UV spectrophotometer by measuring absorbance at ʎ max at 262nm [11]. 
The EE of beads was calculated using this following formula. 
EE = (Actual drug content in beads/Theoretical drug content in beads) x 100  
Determination of buoyancy: 50g of microbeads were placed in 100ml stimulated gastric fluid (SGF, pH 7.4) 
the mixture was stirred at 100rpm on a magnetic stirrer. After 2h, the floating and settled microbeads were 
collected separately, dried at 400ºC and weighed [12] 
Buoyancy = (Weight of floating Microbeads / weight of floating Microbeads+ weight of settled Microbeads) x 
100  
Swelling study: Swelling ratio of different dried microbeads were determined gravimetrically in simulated 
gastric fluid pH 7.4. The microbeads were removed periodically from the solution, blotted to remove excess 
surface liquid and weighed on balance. Swelling ratio (%w/v) was determined [13]. 
4. Result & Discussion  
Percentage yield: 
Formulation %yield 
F1 96.5±1.2% 
F2 95.3±2.3% 
F3 97.1±0.5% 
The percentage yield of formulation F1-F3 ranges from 95.3 to 97.1%. 
Drug entrapment efficiency 
Formulation Entrapment efficiency 
F1 92.3±1.2% 
F2 94.1±1.9% 
F3 93.2±0.8% 
The entrapment efficiency of the formulation F1-F3 ranges from 92.3 to 94.1%. 
 
 
 
To Chemistry Journal Vol 2 (2019) ISSN: 2581-7507                                  http://purkh.com/index.php/tochem 
181 
Determination of buoyancy 
Formulation Buoyancy 
F1 90.3±0.8% 
F2 89.6±0.6% 
F3 84.1±0.9% 
The buoyancy of the formulation F1-F3 ranges from 90.3 to 84.1%. 
Swelling study: 
Formulation Swelling ratio 
F1 212.1±0.8% 
F2 189.1±2% 
F3 302.1±0.3% 
The swelling study of the formulation F1-F3 ranges from 189.1 to 302.1%. 
The results are up to the mark as compared to the standard values. 
5. Conclusion 
A new sustained release system of oil entrapped sodium alginate beads was formulated by an emulsion gelation 
method. Its morphology and release characteristics were studied. The beads were easy to prepare. The pore-
size of oil-entrapped beads was affected by the concentration of the oil. The beads showed excellent sustaining 
properties as compared to the conventional beads. Thus, oil entrapped technique appears to be a useful tool 
for the development of multi-particulate system even for water -soluble drug. The F3 shows the best result 
among all formulations.  
Beads of Metformin HCl are prepared using polymer. Sodium alginate beads has attained highest yield (%) and 
showed maximum drug loading capacity and drug encapsulation efficiency. Swelling index studies shows that 
the beads swelled more in intestinal region. Process parameters such as the polymer concentration, 
polymer/drug ratio, and the amount of hardening agent were analyzed for their influences on the bead 
properties.  
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Development and Characterization of Sodium Alginate Beads for Metformin

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Development and Characterization of Sodium Alginate Beads for Metformin

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