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SK. Masthanamma*et al. /International Journal of Pharmacy & Technology
IJPT| April-2017| Vol. 9 | Issue No.1 | 28590-28606 Page 28590
ISSN: 0975-766X
CODEN: IJPTFI
Available Online through Research Article
www.ijptonline.com STABILITY INDICATING VALIDATED RP-HPLC METHOD FOR SIMULTANEOUS
DETERMINATION OF METFORMIN HCL AND MIGLITOL IN BULK AND PHARMACEUTICAL
DOSAGE FORM
SK. Masthanamma*, SK.Naseema, SK.Reehana, SK.Ammaji
Department of Pharmaceutical Analysis, University College of pharmaceutical science, Acharya Nagarjuna
University, Nagarjuna Nagar, Guntur –522510.Andhra Pradesh (India).
Email: masthanamma.sk@gmail.com
Received on: 14-02-2017 Accepted on: 22-03-2017
Abstract
Aim: a simple, rapid, precise, accurate and economic stability-indicating RP-HPLC assay method was developed and
validated for simultaneous estimation of Metformin HCl, Miglitol bulk drugs and commercial tablets.
Method: The method has shown adequate separation of Metformin HCl and Miglitol from their degradation
products. Separation was achieved on a Zorbax C18 (250mm×4.6mm i.d; 5μm) column at wavelength of 270nm,
using a mobile phase Orthophosphoric acid (0.1%) pH 2.1 and Methanol (50/50 ) in an isocratic elution mode at a
flow rate of 1.2 ml/min.
Results: The retention time for Metformin HCl and Miglitol were found to be 2.751 and 3.894min respectively. The
above drug combinations were subjected to acid, base, neutral hydrolysis, thermal and photolytic stress conditions.
Thus stressed samples were analyzed by the proposed analytical method. Quantitation was achieved with UV
detection at 270 nm based on peak area with linear calibration curves at concentration ranges 50-150μg/ml for
Metformin HCl and 2.5-7.5μg/ml for Miglitol (R2 > 0.999 for both drugs). The LOD’s were 0.005 μg/ml and 0.154
μg/ml for Metformin HCl, Miglitol respectively. The LOQ’s were found to be 0.015μg/ml for MET HCl and
0.4629μg/ml for MIG.
Conclusion:
The method was found to be specific and stability indicating as no interfering peaks of degrades and excipients were
observed. The proposed method is hence suitable for application in quality-control laboratories for quantitative
analysis of both the drugs individually and in combination dosage forms, since it is simple and rapid with good
accuracy and precision.
Keywords: Forced degradation studies, Metformin HCl, Miglitol, RP-HPLC, Stability indicating assay.
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Introduction:
Metformin [1-2] HCl [fig.1] is chemically 1- carbamimidamido-N, N-dimethylmethanimidamide. With molecular
formula C8H17NO5 and 129.16 mg molecular weight. It is most widely prescribed anti-diabetic drug in the world used
to treat type 2 diabetes. Metformin helps to control the amount of glucose (sugar) in blood. It decreases the amount of
glucose and also increases body's response to insulin, a natural substance that controls the amount of glucose in the
blood. It is not used to treat type 1diabetes. It is also used for treatment of gestational diabetes, polycystic ovary
syndrome (PCOS). It works by decreasing hyperglycemia primarily by suppressing glucose production by the liver
(hepatic gluconeogenesis).
It helps to reduce LDL cholesterol and triglyceride levels, and is not associated with weight gain. Metformin comes
as a liquid, as a tablet, and as an extended-release (long-acting) tablet taken orally. It is used alone or with other
medication. Very rare but serious side effect with Metformin is lactic acidosis.
Miglitol [3-4] [fig.2] is chemically (2R, 3R, 4R, 5S)-1-(2-hydroxyethyl)-2-(hydroxymethyl) piperidine-3, 4, 5-triol,
with molecular formula C8H17NO5. Its molecular weight is 236.1363mg.Miglitol inhibits glycoside hydrolase
enzymes called alpha-glucosidases thereby slowing the appearance of sugar in the blood after meal. It works by
slowing down the absorption of carbohydrates from diet, so that blood sugar does not rise as much after meal. Alpha-
glucosidases inhibitors are used to help control blood sugar levels that are not controlled by diet and exercise alone. It
is believed that strict control of blood sugar in people with diabetes decreases the risk of eye, kidney and nerve
damage.
Objective of study: As literature survey reveals that a number of methods were reported for the estimation of these
drugs in bulk and combined dosage form like Simultaneous estimation of Metformin HCl and Miglitol in tablet
dosage form by RP-HPLC [8-23], UV-spectrophotometric method [6-7]. A number of spectrophotometric and
chromatographic analytical methods were reported for the estimation of these drugs in their formulations.
However, these methods lack stability indicating nature. Also, none of the reported procedures enable analysis of
both the drugs in pharmaceutical dosage forms in presence of their degradation products. In the present investigation,
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an attempt was made to develop a simple, rapid, precise and accurate stability indicating RP-HPLC assay method for
simultaneous estimation of Metformin HCl and Miglitol presence of their degradation products This proposed
method can be successfully employed for quality control during manufacture and for assessment of the stability of
both drugs in bulk samples and combined dosage forms.
Materials and Methods:
Drug substance: Metformin HCl and Miglitol (working standard 99.12% and 99.73%) were obtained as gift sample
from Rainbow pharma training lab, Hyderabad, India. Pharmaceutical tablet formulation of MIGNAR25-MFwas
purchased from local pharmacy. Methanol (HPLC Grade, MERCK), Orthophosphoric acid (HPLC grade, MERCK),
Hydrochloric acid (AR grade), sodium hydroxide, hydrogen peroxide (AR grade) and HPLC grade water were used
for the entrained study.
Instrumentation: All HPLC experiments were carried out on a Waters Alliance 2695 separation module, with waters
2996 photodiode array detector in isocratic mode using Auto sampler. Data collection and processing was done using
EMPOWER PDA 2 software. The analytical column used for the separation was Zorbax C18,250× 4.6 mm I.D., 5
μm particle size, Other equipments used were ultra-sonicator (model 3210, Branson Ultrasonic’s Corporation,
Connecticut, USA), Analytical balance (contech balance).
Preparation of solutions
Diluents: Diluents was prepared by mixing solvent A and solvent B (a: b, 50/50)
Preparation of 0.1M Orthophosphoric acid buffer solution: Prepared by dissolve 1ml of OPA with 1000ml of
HPLC grade water.
Mobile phase: Mobile phase was prepared by mixing OPA (0.1%, pH-2.1,) and Methanol (50/50). It was filter to
0.45u membrane filter to remove the impurities otherwise they may interfere in the final chromatogram and it was
sonicated for 15min to remove the undissovable gases and air bubbles.
Preparation of 0.1N HCL
0.1 N HCL was prepared by taking 0.08ml of conc. HCL in 100ml of HPLC grade water.
Preparation of 0.1N NaoH
0.1N NaoH was prepared by taking 0.4mg of NaoH in 100ml of HPLC grade water.
Preparation of Hydrogen peroxide (3%)
Hydrogen peroxide was prepared by taking 3ml of hydrogen peroxide in 100ml of HPLC grade water.
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Standard solution
Standard solutions of Metformin HCl and Miglitol were prepared by dissolving 500mg of Metformin HCl and 25mg
of Miglitol in two separate 50ml volumetric flasks contain 10ml of HPLC grade water in each flask, sonicate for
5min and final volume were made up to the mark with HPLC grade water. From these stock solutions take 2.5ml
from each flask and transfer into two separate 25ml volumetric flasks, the final volumes were made up to the mark
with HPLC grade water to get the concentrations of 1005µg/ml of Metformin HCl and 0.55µg/ml Miglitol
respectively.
Chromatographic conditions: The mobile phase was a mixture of OPA (0.1%, pH 2.1) and Methanol (50/50 v/v).
The contents of the mobile phase were filtered, before it was used, through 0.45 μm membrane filter, degassed with a
helium spurge for 15 min and pumped from the respective solvent reservoirs to the column at a flow rate of 1.2
ml/min, Zorbax C18 (250*4.6mm I.D, 5μm. The column temperature was maintained at 30oc and run time 20mins.
The injection volume of samples was 10μL. The analyte was monitored at 270nm. The chromatographic conditions
were shown in Table.1.and obtained chromatogram shown in fig.3.
Figure.3. Optimised chromatography.
Method Development:
To saturate the column, the mobile phase was pumped for about 30 minutes thereby to get the base line corrected.
After no. of trials optimum chromatographic conditions were fixed for better separation. The separate standard
calibration lines were constructed for each drug. A series of aliquots were prepared from the above stock solutions
using HPLC grade water to get the concentrations 50-150 5µg/ml Metformin HCl and 2.5-7.5µg/ml Miglitol. Each
concentration 6 times was injected into chromatographic system. Each time peak area and retention time recorded
separately for both the drugs. Calibration curves were constructed by taking average peak area on y-axis and
concentration on x-axis separately for both the drugs. From the calibration curves regression equations were
calculated as shown in the figure no.4 & 5.
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Fig.4. Calibration curve of Metformine HCl
Fig.5. Calibration curve of Miglitol
Estimation of Metformin HCL and Miglitol in Tablet Dosage Form:
For the analysis of drugs, 20 tablets were weighed and triturated in a glass mortar and quantity of powder equivalent
to 500mg of Metformin HCl was transferred to 50ml volumetric flask and dissolved in sufficient quantity of HPLC
grade water. It was sonicated for 5mins and volume was made up to 50ml HPLC grade water. It was filter through
0.45μ membrane filter. From this solution transfer 2.5ml into 25ml volumetric flasks, the final volume were made
up to the mark with HPLC grade water to get the concentrations of 100μg/ml of Metformin HCl and 5μg/ ml of
Miglitol respectively.
The test concentration is injected 6 times in to chromatographic system. Each time peak area and retention time was
recorded and the results obtain were as shown in the table no.2.
Table.2: Results of Marketed Formulation analysis:
Drug name Lablled
claim(mg)
Test
concentratio
n(µg/ml)
Meam Amt
found
(µg/ml) (n=6)
% Estimated
Amt
Metformin HCl
500
50
49.75
99.51
Miglitol
25
2.5
2.42
96.8
Method validations: The analytical method was validated for various parameters as per ICH guidelines.
y = 16039x + 261.1R² = 0.999
0
500000
1000000
1500000
2000000
2500000
3000000
0 50 100 150 200
Ряд1
Линейная (Ряд1)
y = 385172x 505.14R² = 0.999
-1000000
0
1000000
2000000
3000000
4000000
0 2 4 6 8
Are
a
Concentration (µg/ml)
Ряд1
Линейная (Ряд1)
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Linearity
The linearity of the method was determined in concentration range of 50-150 μg/ml for MET HCl and 2.5-7.5μg/ml
for MIG. Each solution was injected in triplicate. The average peak area versus concentration data of both drugs was
treated by least squares linear regression analysis. Linearity was checked over the same concentration range on three
consecutive days and the results obtained from as shown in tableno.3.
Table.3: Linearity studies results
Parameters MET HCl MIG
Linearity range (µg/ml)
Regression line equation
Correlation coefficient (r)
No of data points
LOD (µg/ml)
LOQ (µg/ml),%RSD
50-150
y = 16039x + 261.14
0.999
5
0.005
0.015,0.44
2.5-7.5
y =385172x + 505.14
0.999
5
0.1543
0.4629,0.35
Specificity and Selectivity
Specificity is the degree to which the procedure applies to a single analyte and is checked in each analysis by
examining blank matrix samples for any interfering peaks. The specificity of the method was evaluated with regard to
interference due to presence of any other excipients. Two different samples were injected and studied with respective
excipients. The HPLC chromatograms recorded for the drug matrix (mixture of the drug and excipients) showed
almost no interfering peaks with in retention time ranges. Fig. 6 & 7 show the respective chromatograms for MET
HCl and MIG with Blank and Placebo. The figures shows that the selected drugs were cleanly separated. Thus, the
HPLC method proposed in this study was selective.
(a) (b)
Fig.6 (a). Specificity chromatogram with Blank (b) Specificity chromatogram with Placebo
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a b
c d
e
Fig.7 (a-e): a) Acid Degraded sample b) Base Degraded sample c) Thermal degraded sample d) Peroxide
degraded sample e) Photo degradation sample.
Accuracy, as Recovery
Accuracy was evaluated in triplicate, at three different concentrations equivalent to 50, 100, and 150% of the target
concentration of active ingredient, by adding a known amount of each of the Standard to a sample of known
concentration of both drugs and calculating the % of recovery, and the results obtained from as shown in table no.4.
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Table.4: Accuracy studies results
Drug
name
Pre analysed
concentratio
n taken
(µg/ml)
Recovery
level
Amt of drug
added(µg/ml)
Amt of
drug
found
(µg/ml)n
=3
%recovery Acceptece
criteria
Metformin
HCl
50
50 25 74.35 99.13 97-103%
100 50 99.58 99.58 97-103%
150 75 124.06 99.24 97-103%
Miglitol
2.5
50 1.25 3.55 94.66 97-103%
Precision:
Precision is the degree of repeatability of an analytical method under normal operational conditions. Precision of the
method was determined with the standard and test sample. The precision of the method was verified by repeatability
and the intermediate precision studies. Method repeatability was achieved by repeating the same procedure of
preparation of solution six times and injecting. Intermediate precision was performed by performing the same
procedure on the same day for intra-day precision. The inter day precision of the method was checked by performing
same procedure on different days under same experimental conditions.
The repeatability of sample application and measurement of peak area were expressed in terms of relative standard
deviation (%RSD) and results obtained were as shown in table no.5.
Table.5: Precision studies results.
Day of analysis %Recovery±SD; %RSD
Intraday Precision
Metformin HCl
(µg/ml)
25 50 75
0.44 Day0 99.13±0.03 94.66±0.31 99.13±0.03
Day1 99.58±0.03 99.0±0.21 99.58±0.03
Day2 99.24±0.33 97.92±0.18 99.24±0.33
Miglitol (µg/ml) 1.25 2.5 3.75
Day0 94.66±0.31 94.66±0.31 94.66±0.31
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Day1 99.0±0.21 99.0±0.21 99.0±0.21 0.35
Day2 97.92±0.18 97.92±0.18 97.92±0.18
Interday Precision
HYD HCl (µg/ml) 25 50 75
Day0,1,2 99.13±0.03 97.92±0.18 99.13±0.03 0.44
ISD (µg/ml) 1.25 2.5 3.75
Day0,1,2 99.0±0.21 99.0±0.21 97.92±0.18 0.35
LOD and LOQ
The Limit of Detection (LOD) and Quantitation (LOQ) for both MET HCl and MIG were determined using standard
deviation method according to ICH guidelines Q2 (R1).
LOD is lowest amount of analyte in a sample that can be detected but not necessarily quantities as an exact value
under the stated experimental conditions. The detection limit is usually expressed as the concentration of analyte. The
standard deviation and response of the slope
LOD = 3.3*standard deviation (ϭ)/s
The LOQ of an analytical procedure is the lowest amount of an analyte of a sample which can be quantitatively
determined with suitable precision and accuracy. The standard deviation and response of the slope and the results
obtained were as shown the table no.6
Table.6: LOD and LOQ results
Drug name Area Retention time LOD LOQ
Metformine HCl 1604472
2.751 0.005 0.015
Miglitol 1925126
3.894 0.1543 0.4629
LOQ= 10* standard deviation (ϭ)/s
Robustness:
To evaluate the robustness of the method, the chromatographic conditions were deliberately
Altered and degree of reproducibility was evaluated. During robustness testing each condition
was varied separately, all other conditions being held constant at the optimized values. Robustness of the proposed
method was assessed with respect to small alterations in the flow rate (1.2± 0.1ml/min), and Temperature (300c ± 2
0c)
and the results obtained were as shown the table no.7.
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Table.7: Robustness studies results
Method
Parameters
Conditios Retention Time(Rt) Area %Recovery
MET HCl MIG MET HCl MIG MET
HCl
MIG
Temp1 28 2.877 3.893 303455 5685582 99.13 94.66
Temp2 30 2.677 3.592 3081475 5688522 99.58 99.00
Temp3 32 2.531 3.365 301354 542285 99.24 97.92
Flow1 1.1 3.352 4.486 3898117 7359125 94.66 99.13
Flow2 1.2 2.228 2.999 2515860 4721091 99.00 99.58
Flow3 1.3 2.105 2.513 250685 4686218 97.92 99.24
System suitability parameters
For assessing system suitability, six replicates of working standards samples of MET HCl and MIG were injected and
studied the parameters like plate number(N), tailing factor(K),resolution, relative retention time and peak asymmetry
of samples. The results were show in tableno.8.
Table.8: System suitability parameters of MET HCl and MIG.
Parameters
Values obtained (n=6)
MET HCL MIG
Plate count 8888 13293
Tailing Factor 1.15 1.22
Rt (min) 2.75 3.89
resolution 0 8.87
Asymmetry 1.3 1.4
Degradation sample Preparation
Weigh accurately 20tablets and crush into fine powder from this take 100mg (equivalent to 50mg MET HCl 2.5mg
MIG) of powdered sample into a 100ml volumetric flask dissolve and dilute to volume with HPLC grade water and
filter the solution using 0.45µ Nylon filter.
Acid hydrolysis
Transfer 1ml (500ug/ml MET HCl) of above stock solution to10ml volumetric flask and add 1ml of 0.1N HCL and
reflux for 30min at 600c .cool to room temperature and neutralize with 1ml of 0.1N NaoH and makeup volume with
HPLC grade water.
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Base Hydrolysis
Transfer 1ml (500ug/ml MET HCl) of above stock solution to10ml volumetric flask and add 1ml of 0.1N NaoH and
reflux for 30min at 600c .cool to room temperature and neutralize with 1ml of 0.1N HCl and makeup volume with
HPLC grade water.
Peroxide hydrolysis
Transfer 1ml (500ug/ml of MET HCl) of above stock solution to10ml volumetric flask and add 1ml of 3%v/v of H202
and reflux for 30min at 600c .Cool to room temperature and makeup volume with HPLC grade water.
Thermal Degradation
Weigh accurately 20tablets and crush into fine powder and transfer powder to 200mg (equivalent to 100mg MET HCl
and 5mg MIG) powder into petridish. Heat the sample in oven for about 6hrs at 1050c. From this weigh accurately
100 mg of powdered sample into a 100ml volumetric flask dissolve and dilute to volume with HPLC grade water.
Transfer 1ml of above stock solution to10ml volumetric flask and filter the solution using 0.45µ Nylon filter.
Photolytic Degradation
Photolytic degradation study was carried out by exposing the accurately weighed 200mg (equivalent to 100mg MET
HCl and 5mg MIG) of tablet powder to UV light in a photolytic chamber at 2600 lux for 24 hr, After 24hrs weigh
accurately 100 mg of powdered sample into a 100ml volumetric flask dissolve and dilute to volume with HPLC grade
water .Transfer 1ml of above stock solution to10ml volumetric flask and filter the solution using 0.45µ Nylon filter.
Using the peak purity test, the purity of the drugs peaks were checked at every stage of above-mentioned studies.
Forced Degradation Studies
Stress-degradation studies of the drug substances can help identifying the possible degradation products which can in
turn help establishing the degradation pathways and the intrinsic stability of the molecule and validate the stability-
indicating power of the analytical procedures used. The chromatograms of Metformin HCl and Miglitol, after being
subjected to different mild and drastic degradation conditions, were compared with blank solutions injected in a
similar manner and with recently prepared solutions. These results showed the specificity of the developed method
clearly. The results indicated that in the stressed degradation studies using the optimized methods, degradation peaks
for MET HCl and MIG did not affect the drug peak. The mass balance of Metformin HCl and Miglitol under each
stress condition was found 100% and, moreover, assay of each unaffected compound in the tablets confirmed the
stability indicating nature of the method. MIG was relatively more labile than MET HCl in photolytic and thermal
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degradative conditions while MIG was more susceptible than MET HCl in acidic, basic, neutral and oxidative. The
results from forced degradation studies were summarized in Table no.9.Representative Chromatograms obtained
from forced degradation studies are shown in Fig.7a-e).
Table.9: Forced Degradation Studies
The degradation behavior and degradation products of MET HCL and MIG were found to be similar in combination
drug product and in bulk drugs under various stress conditions assessed. The study was not intended to identify
degradation products but merely to show they would not interfere if and when present. To conclude, the results of
stress testing studies indicate a high degree of specificity of this method for both MET HC land MIG.
Solution stability
The stock solution showed no significant change in analyte composition, retention time and peak areas of MET HCl
and MIG after 1 weeks of storage at room temperature. This was sufficient for the whole analytical process
Results and Discussion
Optimized chromatographic conditions:
Most of all reported HPLC methods till date use C-8 or C-18 columns. Most of these uses
Complex mobile phase compositions. Hence, attempts were directed towards development of a Simple and better
method on commonly used C18 column with good resolution. Different logical modifications were tried to get good
separation among the drugs and the degraded products. These changes included change in mobile phase composition
in isocratic elution as well as gradient modes on different C18 columns.
The optimized chromatographic conditions (fig.3).The best peak shape and maximum separation was achieved with
mobile phase consist of 0.1%OPA (pH 2.1) and methanol (a: b, 50/50). Peak symmetry and reproducibility were
obtained on Zorbax C18, 250mm×4.6mm I.D; 5μm).The detection wavelength at 270nm, a flow rate of 1.2ml/min
yielded optimum separation and peak symmetry as shown table 1.
Stress conditions
Metformin HCl Miglitol
% degradation % degradation
Acidic/0.1 M HCl/60°C reflux/48 h 5.9 11
Basic/0.1 M NaOH/60°C reflux/48 h 7.5 0.0
Oxidizing/3% H2O2/cool at RT/30min 10 14
Thermal/105°C/6hr 4.2 0.0
Photolysis/UV light 6.2 0.0
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Table.1: Optimized Chromatographic conditions:
Column Zorbax 250*4.6mm,5µm
Flow rate 1.2ml/min
Wavelength 270nm
Column temperature 30oc
Injection volume 10µl
Run time 20min
Diluents HPLC grade water
Elution Isocratic
Mobile phase 0.1%OPA (pH 2.1),Methanol(50/50 v/v)
Degradation studies
Results are tabulated in table no.9.
Acid hydrolysis (figure 7 a)
Upon performance of acid degradation studies 98% of Metformin HCl and 94% of Miglitol was degraded.
Base hydrolysis (fig.7b)
Upon performance of base degradation studies 96% of Metformin HCl and 93% of Miglitol was degraded.
Peroxide hydrolysis (fig.7c)
Upon performance of peroxide degradation studies 98% of Metformin HCl and 94% of Miglitol was degraded.
Thermal degradation (fig.7d)
Upon performance of Thermal degradation studies 97% of Metformin HCl and 98% of Miglitol was degraded.
Photolytic degradation (fig.7e)
Upon performance of Photolytic degradation studies 97% of Metformin HCl and 98% of Miglitol was degraded.
Linearity, LOD and LOQ
The calibration plot was linear over the concentration range investigated (50-150μg/ml; n = 3) and (2.5-7.5μg/ml; n =
3) for MET HCl and MIG respectively (figure 7, 8). Average correlation co-efficient r=0.9999 for both drug
candidates with %RSD values ≤2.0 across the concentration ranges studied, was obtained from regression analysis.
The LOD for MET HCl and MIG were found to be 0.005μg/ml and 0.1543μg/ml respectively. The LOQ that
produced the requisite precision and accuracy was found to be 0.015μg/ml for MET HCl and 0.4629μg/ml for MIG.
The resultant %RSD values were ≤1.00 %( table no.5).The regression results indicate that method was linear in the
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concentration range studied (table .5) and can be used for detection and quantification of MET HCl and MIG in a
very wide concentration range.
Accuracy and Precision
Accuracy as recovery was evaluated by spiking previously analyzed test solution with additional Standard drug at
three different concentration levels (table-3). Recovery of standard drugs added was found to be 99.31% for
Metformin HCl and 97.19% for Miglitol with the value of RSD less than 1% indicating that the proposed method is
accurate for the simultaneous estimation of both drugs from their combination drug products in presence of their
degradation products. The low RSD values indicate the repeatability and reproducibility of the Method (table 4).
Robustness
Results of the robustness (table.7) study are depicted in Table no.3. The elution order and resolution for both
components were not significantly affected. RSD of peak areas were found to be well within the limit of 2.0%.
Discussion
A simple, rapid, accurate and precise stability-indicating HPLC analytical method has been
developed and validated for the routine quantitative analysis of Metformin HCl and Miglitol in API and combined
dosage forms. The results of stress testing undertaken according to the ICH guidelines reveal that the method is
specific and stability-indicating. The proposed method has the ability to separate these drugs from their degradation
products in tablet dosage forms and hence can be applied to the analysis of routine quality control samples and
samples obtained from stability studies.
Conclusion
A simple, rapid, accurate and precise stability-indicating HPLC analytical method has been developed and validated
for the quantitative analysis of Metformin HCl and Miglitol in bulk drugs and combined dosage forms. Stress testing
(or forced degradation studies) is an important part of drug development process and the pharmaceutical industry has
much interest in this area. The results of stress testing undertaken according to the ICH guidelines reveal that the
method is specific and stability-indicating. The proposed method has the ability to separate these drugs from their
degradation products in tablet dosage forms and hence can be applied to the analysis of routine quality control
samples and samples obtained from stability studies.
Acknowledgment: Authors are very thankful to principal, University College of pharmaceutical sciences, Acharya
Nagarjuna University, Guntur, for providing the library facilities for literature survey to carryout entire study.
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Authors also thankful to Rainbow pharma training lab, Hyderabad, India, for providing Metformin HCl and Miglitol
working standard as gift sample and HPLC Instrument to carry out Research work.
References
1. Available from: http://www.drugbank.ca/drugs/DB01275 Metformin.
2. Available from: http://en.wikipedia.org/wiki/Metformin.
3. Available from: http://www.drugbank.ca/drugs/DB00883 Miglitol.
4. Available from: http://en.wikipedia.org/wiki/Miglitol.
5. Arayne MS, Sultana N, Zuberi MH, Siddiqui FA. Spectrophotometric Quantitation of Metformin in Bulk Drug
and Pharmaceutical Formulations using Multivariate Technique. Indian journal of pharmaceutical sciences 2009;
71(3):331-5.
6. Narasimha RD, Prasada RM, Hussain J, Sumanoja S, Rajeswara RV. Naga Lakshmi. Method development and
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