ISSN: 0975-766X CODEN: IJPTFI Available Online through ... · drugs in bulk and combined dosage form like Simultaneous estimation of Metformin HCl and Miglitol in tablet dosage form

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: [email protected]

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,



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.



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.



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)



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



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.



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



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.



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.



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



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



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



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.



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.

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