Research Article

A comparative study on effect of polymers on release kinetics glimepiride matrix tablet

Sonia Chowdhury*, Mandava Nithin Babu, K. Ankitha, B. Shirisha, Madhurika Sirigadi, Esarapu Kavya

School of Pharmacy, Anurag Group of Institutions, Venkatapura, Hyderabad, India

*For correspondence

Sonia Chowdhury,

School of Pharmacy, Anurag Group of Institutions, Venkatapura, Hyderabad, India.

Email: dibyalochan.mohanty






Received: 19 February 2017

Revised: 18 March 2017

Accepted: 20 March 2017


Objective: The Present investigation was performed to find out the effect of synthetic and natural polymers on the release properties of glimepiride matrix tablet. Glimepiride is a first third generation sulphonyl urea agent for the treatment of type- II diabetes mellitus. Methocel K15M, Olibanum Gum were used as key release modifying polymers.

Methods: Nine formulations were prepared taking different concentration of natural and synthetic polymers, The drug excipient mixtures were subjected to pre-compression studies. The tablets were prepared by direct compression method; all formulations were subjected to physicochemical studies, in- vitro drug release, kinetic studies and stability studies. The physicochemical results were found within the limits.

Results: FTIR study interpretation did not show any drug–excipient interaction The drug release from the optimized formulation F-7 was extended for a period of 12 hours. The release kinetics of F-7 formulation showed that the release of drug follows zero order models. The optimized formulations were subjected to stability studies and shown there were no significant changes in drug content, physicochemical parameters and release pattern.

Conclusions: Results of the present study indicated the suitability of the above mentioned polymers in the preparation of sustained release formulation of Glimepiride for the management of type-II diabetes mellitus effectively.

Keywords: Sustained release, Glimepiride, FTIR


Matrix Tablets are one of the approach to Sustained the drug release for longer period of time at expected rate after its single dose administration.1 When highly water soluble drugs are prepared as oral sustained release dosage form cause problems like they may be released more rapidly and result in toxicity if not prepared in appropriate fashion.3 Many methods are there to formulate oral sustained release dosage form among which matrix system is most appropriate due to consistency, validation, scale up and cost effective. Conventional immediately release dosage forms sometimes associates with fluctuating drug levels in therapeutic zone which may lead to precipitation of adverse effect especially of drugs with small therapeutic index.2 The Matrix system present a variety of benefits above conventional dosage forms that include decrease in dosage rate, patient ease, minimum toxicity and improved patient compliance.4 On the other hand, more constant level of drug in the blood constant flow with minimum peak-valley is reached, achieve greater efficacy. Forms release drugs according to criminal order which produces the rise and fall of drug concentrations and therapeutic level change. While dosage forms with controlled release of the drug release rate to zero, which gives order a steady drug concentration.5

Diabetes mellitus is mainly classified as four types. They are, Type -I, Type –II, Gestational diabetes, other types of diabetes.6 Glimepiride is the first III generation sulphonyl urea it is a very potent sulphonyl urea with long duration of action.7 It is practically insoluble in water. Soluble in dimethyl formamide, slightly soluble in methanol, sparingly soluble in methylene chloride. The biological half-life is approximately 5 hours following single dose. Completely absorbed following oral administration. Over 99.5% bound to plasma protein. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. The mechanism of action of Glimepiride in lowering blood glucose appears to be dependent on stimulation the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin.8 The aim of the present work was to prepare sustained release matrix tablets of glimepiride by using various concentrations of natural and synthetic polymers (Methocel K15M, Olibanum Gum) by direct compression method and to study the effect of in-vitro release characteristics, kinetics of the prepared formulations and stability studies.

Figure 1: Structure of Glimepiride.

Materials and Methods

Glimepiride was procured as a gift sample from MSN Lab, Hyderabad, India. Methocel K15M and PVP K30 were purchased from Cardila Healthcare Limited, Gujurat, India. Olibanum Gum was purchased from Loba Chemie Pvt. Ltd, Mumbai. Magnesium stearate and Talc were purchased from Granules India Hyderabad.

Experimental methods

Preparation of the standard calibration curve of Glimepiride in pH 6.8 Phosphate buffer

Glimepiride (50 mg) was dissolved in 20 ml of phosphate buffer pH6.8 and volume was made up to 100 ml in volumetric flask using phosphate buffer pH6.8. From this stock solution 10 ml was withdrawn and diluted to 50 ml in volumetric flask which gives the concentrations of 100 μg/ml. From this stock solution aliquots were withdrawn in volumetric flask to give concentrations of 6-14 μg/ml. absorbance of each solution was measured at 226 nm using UV-Vis double beam spectrophotometer with phosphate buffer pH 6.8 as reference standard.

Drug-excipient compatibility studies

Assessment of possible incompatibilities between an active drug substance and different excipients forms an important part of the pre-formulation stage during the development of solid dosage form. Therefore, the pure drug and the formulations mixed with polymers were subjected to infra-red (IR) studies

Fourier transform infrared (FTIR) spectral analysis

The compatibility of drugs and excipients used under experimental condition were studied. The study was performed by preparing KBr pellets with the help of KBr press taking 1 mg sample in 100 mg KBr. The scanning range was 400 to 4000 cm-1 and there solution was 1cm-1. This spectral analysis was employed to check the compatibility of drugs with the excipients used.

Preformulation studies of powder blend

Table 1: Formulation table of Glimepiride matrix tablet.

Ingridients (mg) F1 F2 F3 F4 F5 F6 F7 F8 F9
Glimepiride 8 8 8 8 8 8 8 8 8
Methocel K15M 60 70 80 - - - 40 45 50
Olibanum Gum - - - 55 65 75 40 45 50
PVP K-30 30 30 30 30 30 30 30 30 30
Lactose 48 38 28 53 43 33 28 18 8
Magnesium Sterate 2 2 2 2 2 2 2 2 2
Talc 2 2 2 2 2 2 2 2 2
Total 150 150 150 150 150 150 150 150 150

Flow characteristics of different powder blend is very important for developing and designing an optimized formulation. In order to determine the flow characteristics of powder blend different test such as angle of repose, bulk density, tapped density, compressibility index and Hausner's ratios were determined according to the standard procedures given in USP.

Figure 2: Standard calibration curve of glimepiride in ph 6.8 at 226 nm.

Formulation of Glimepiride matrix tablet9

Glimepiride matrix tablet was prepared by direct compression method. Sustained release matrix tablets of glimepiride were prepared by using rate modifying matrix forming polymers like Methocel K15M, Olibanum Gum in different concentration, PVP K-30 used as binder, lactose as a diluent, magnesium stearate as a lubricant and talc as an anti-adherent. All ingredients used were passed through a # 100 sieve, weighed and blended. The individual formulations were compressed by using 10 mm flat faced punches using in a rotary tablet press (Rimek minipress, model RSB-4, M/S: Karnavathi engineering, Ahmadabad).

Evaluation of physical characteristics of matrix Glimepiride tablet10-12

Weight variation

The weight variation test was performed by weighing 20 randomly selected tablets individually, the average weight of tablet was calculated and using the formula of weight variation, the % weight of variation according to I.P was calculated. The specification of weight variation is 10%.


Hardness test

The formulated matrix tablet was evaluated for its hardness using Monsanto Hardness tester, ten tablets were randomly picked from each formulation and the mean and standard deviation values were calculated. The hardness was expressed in kg/cm2.


A friability test was conducted to know the powder lose in the formulated tablets using a Roche friabilator. Twenty tablets were selected from each batch and any loose dust was removed with the help of a soft brush. The tablets were initially weighed (Winitial) and transferred into friabilator. The drum was rotated at 25 rpm for 4 minutes after which the tablets were removed. Any loose dust was removed from the tablets as before and the tablets were weighed again (Wfinal). The percentage friability was then calculated by the formula

F % = × 100

Uniformity of thickness

The tablet thickness was measured using screw gauge.

Drug content uniformity

Five tablets of each formulation were weighed and powdered. The quantity of powder was equivalent to 8 mg. The equivalent weight of glimepiride was transferred into 100 ml volumetric flask and by using pH 7.8 as the extracting solvent and samples was analyzed spectrophotometrically by using UV/ Visible spectrophotometer at 226 nm.

In- vitro drug release studies13

Dissolution studies were carried out for all the formulations combinations in triplicate, employing USP - II dissolution apparatus, in this method 900ml of pH 7.8 phosphate buffer as the dissolution medium. The medium was allowed to equilibrate to temp of 37°C±0.5°c. Tablet was placed in the vessel and the vessel was covered the apparatus was operated for 24 hours in pH 7.8 phosphate buffer at 50 rpm. At definite time intervals of 5 ml of the aliquot of sample was withdrawn periodically and the volume replaced with equivalent amount of the fresh dissolution medium. The samples were analyzed spectrophotometrically at 226 nm using UV spectrophotometer. And this dissolution data was further treated for kinetic modeling.

Kinetics of in-vitro drug release14

To study the drug release kinetics in-vitro release data was applied to kinetic models such as zero-order, first order, Higuchi and Korsemeyer-Peppas.


In zero order drug release describes the rate of drug release doesn't depend on intial concentration

Zero order kinetics is expressed by following equation

C = K o t (1)

In zero order kinetics the graph is plotted between amount of drug release and time


The first order kinetics is represented by following equation

Log C = log Co – Kt /2.303 (2)

Where C is the concentration, Co is the initial concentration of drug, K is the first-order rate constant, and t is the time. The data obtained are plotted as log cumulative percentage drug remaining verses time,


The basic equation of Higuchi model is

Qt = KH ·t1/2 (3)

Where Qt is the amount of release drug in time t, K is the kinetic constant and t is the time in hrs.

Korsmeyer peppas

Mt / M  = K · t n (4)

Where Mt represents amount of the released drug at time t, M is the overall amount of the drug (Whole dose). The value of n indicates the drug release mechanism related to the geometrical shape of the delivery system, if the exponent n = 0.5, then the drug release mechanism is Fickanian diffusion. If n < 0.5 the mechanism is quasi-Fickanian diffusion, and 0.5 < n < 0.5, then it is non- Fickanian or anamolous diffusion and when n = 1.0 mechanism is non-Fickanian case ІІ diffusion, n > 1.0 mechanism is non- Fickanian super case ІІ.

Accelerated stability studies15

Accelerated stability study was done to evaluate the effect of temperature and relative humidity on selected formulation (F7), by keeping at 40°± 2°C, in air tight high density polyethylene bottles for three months, at RH 75±5%. Physical evaluation was carried out in each month.

Results and Discussion

Compatibility study

Spectra of the pure drug, excipient and physical mixture of drug and excipient were recorded in between 400-4000 wave number (cm-1). The FTIR spectral analysis showed that there is no appearance or disappearance of any characteristic peaks of pure drug glimepiride and in the physical mixture which confirms the absence of chemical interaction between drug and polymers.

Table 2: FTIR interpretation.

Sl no Peak in pure drug Peaks in optimum formulation
1 NH stretching at 3369 cm -1 NH stretching at 3368 cm -1
2 C-H stretching at 2932-2842 cm -1 C-H stretching at 2932-2843 cm -1
3 C=O stretching at 1707 cm -1 C=O stretching at 1706 cm -1
4 C-N stretching at 1542 cm -1 C-N Stretching at 1543 cm -1

Table 3: Precompression results of formulations F1- F9.

Fomulations Angle of Repose (Degree±SD) Tapped Density (g/mL±SD) Bulk Density (g/mL±SD) Hausner'sRatio (%±SD) Carr's Index (%±SD)
F1 22.37±0.03 0.279±0.03 0.250±0.04 1.13±0.04 14.17±0.01
F2 21.09±0.33 0.284±0.02 0.279±0.03 1.03±0.01 13.79±0.04
F3 23.88±0.04 0.262±0.01 0.259±0.03 1.17±0.03 12.78±0.02
F4 20.42±0.02 0.258±0.02 0.241±0.06 1.15±0.01 13.77±0.02
F5 26.17±0.01 0.261±0.03 0.250±0.04 1.14±0.02 15.07±0.03
F6 25.77±0.03 0.269±0.04 0.258±0.02 1.11±0.04 14.77±0.04
F7 23.11±0.01 0.278±0.03 0.267±0.02 1.17±0.05 12.97±0.06
F8 24.07±0.03 0.278±0.06 0.269±0.03 1.11±0.04 13.87±0.03
F9 26.22±0.02 0.277±0.04 0.261±0.02 1.12±0.05 14.67±0.03

Table 4: Post-compression results of Glimepiride matrix tablet formulations F1-F9.

Fomulations Weight Variation (mg) Hardness (kg/cm2) Drug Content (%) Friability (%) Thickness (mm)
F1 150 3.36 99.12 0.08 3.65
F2 149 3.39 98.75 0.05 3.76
F3 151 4.01 97.62 0.33 3.87
F4 149 3.37 99.73 0.01 3.91
F5 151 3.39 97.33 0.54 3.88
F6 150 4.03 99.21 0.67 3.91
F7 151 4.01 99.43 0.31 3.89
F8 149 3.38 99.32 0.32 3.86
F9 149 3.39 99.46 0.32 3.91

Table 5: In-vitro drug release results of Glimepiride Matrix Tablet.

Time (hour) F1 F2 F3 F4 F5 F6 F7 F8 F9
0 0 0 0 0 0 0 0 0 0
0.5 30.23 41.33 33.47 46.33 23.47 32.57 21.43 29.23 20.43
1 52.61 53.66 42.66 59.66 32.16 52.66 39.71 32.62 49.71
2 61.74 76.84 51.84 78.84 41.64 68.84 42.63 51.74 52.23
3 88.96 91.96 69.59 89.96 59.59 80.59 53.96 76.98 63.96
4 92.34 96.34 78.34 92.64 78.34 89.34 71.21 86.77 77.11
6 98.61 99.91 88.61 95.91 90.51 98.61 79.99 98.67 89.99
8     96.89 98.99 97.29 99.32 88.87   98.17
10     99.12       96.33    
12             99.87    

Preformulation studies

The blends powder all the formulations were subjected for various pre-compressional evaluations such as angle of repose, bulk and tapped density, compressibility index and Hausner's ratio. Results of all the pre-compressional parameters performed are represented in Table 3.

The angle of repose was found to be ranging from 20.420±0.02 to 26.22±0.02 for the powders of all the formulations. Carr's index was found to be ranging from 12.78±0.02 to 15.07±0.03 % for the powders of all the formulations. The results of Hausner's ratio were found to be lesser than 1.20 which indicates better flow properties. The results of angle of repose (<30) indicates good flow properties of the powder. This was further supported by lower compressibility index values. Generally compressibility values up to 15% results in good to excellent flow properties.

Figure 3: FTIR of pure Glimepiride.

Figure 4: FTIR of formulation F-7.

Figure 5: Drug release profile of Glimepiride matrix tablet (F1- F9).

Figure 6: Zero order drug release plot for F7.

Evaluation of prepared Glimepiride matrix tablets

The results of physical evaluation of tablets were given in Table 4. The tablets of different batches were found uniform with respect to hardness within the range of 3.36 to 4.01kg/cm2. Another measure of a tablet's strength is friability. Conventional compressed tablets that lose less than 1% of their weight are generally considered acceptable. Results of friability test were also has been found within limit. All the formulations were found to comply with the specifications given in I.P. for weight variation test. Good uniformity in drug content was found among the formulations, and percentage of drug content was more than 95%. All the tablet formulations showed acceptable pharmaco technical properties.

Figure 7: Huguchi drug release plot for F7.

Figure 8: First order drug release plot for F7.

Figure 9: Korsmeyer plot for F7.

In - vitro drug release study

The formulated matrix tablet of glimepiride was evaluated for the drug release profile by using USP-2 dissolution apparatus .the drug release profile of 9 formulation are given in Table 5, the drug release profile of each formulation is given in Figure 5 based on the results of release profile it was found that with the increase of Methocel K15 gradually the release profile of formulation F1 to F3 had been improved over the time, F3 is showing 99.12% drug release in 10 hour whereas F1 showing 98.61% drug release in 6 hour only. Formulation F4 to F6 containing Olibanum Gum as a key release modifying polymer also showing increase in drug release in a sustained manner over the time. The release profile of glimepiride from different batches of formulated matrix tablets were illustrated in Table 5. The combination of two polymers (Methocel K15 and Olibanum Gum) was taken and to some extent the polymers concentration was increased, the drug release was extended for a period of 12 hours. It is due to the reason that used concentrations of polymers have increased the viscosities of formulations which lead to the sustained-release of drug. The F-7 formulation shown maximum amount of drug release i.e. 99.87 % for a period of 12 hours in a sustained-manner and hence was considered as the best formulation. It was also found to be optimum for stability studies.

Drug release kinetics study

The kinetic release data of optimized F-7ormulations are graphically represented in Figures 5-9. In order to determine the mechanism of drug release form the formulations, the in-vitro dissolution data was fitted to Zero order, first order, Higuchi plot and Korsemeyerpeppa's plot was drawn for optimized formula F-7. The results of R2 for zero and first order were obtained as 0.905 and 0.841 respectively. Based on that we have confirmed that the optimized formulation followed zero order release. Higuchi's model was applied to the in-vitro release data, linearity was obtained with high 'r' value indicating that drug release from the sustained-release tablets through diffusion.

Stability studies

The results of accelerated stability studies carried out according to ICH guidelines indicated that the tablets did not show any physical changes (color change, friability and hardness), assay and dissolution characteristics during the study period.


The study was undertaken with the aim to formulate and evaluate matrix tablets of glimepiride using various concentrations of polymers. From the above results and discussion, it is concluded that F-7 formulation of Matrix tablet of glimepiride containing Methocel K15M and Olibanum Gum in (1:1) ratio showed 12 hours drug release profile in a sustained manner. From the kinetic studies it was known that all the formulations of F-7 released at zero-order rate and were even found to be optimum for stability studies.


Authors thank to Anurag Group of Institutions, Hyderabad for providing Research Facilities. The authors are also thankful to Dr. Vasudha Bakshi Principal of School of Pharmacy, AGI for their valuable suggestion in carrying out this research work.

Funding: No funding sources

Conflict of interest: None declared


  1. Sastry SV, Nyshdham JR, Fix JA. Recent technological advances in oral drug delivery: A review. Pharm Sci and Tech Today. 2000;3:138-45.
  2. Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics, A Treatise. 2010: 335.
  3. Gilbert Banker S. Modern Pharmaceutics, 4th edition, Published by: Marcel Dekker. 2006: 297-321.
  4. Patel R, Baria A. Formulation development and process optimization of theophylline sustained release matrix tablet. Int J of Pharmacy and Pharm Sci. 2009;1(2),30-42.
  5. Rother KI. "Diabetes treatment – bridging the divide". The New Eng J Med. 2007;15:1499-1501.
  6. Wild S, Roglic G, Gree A, Sicree R, King H. Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047-53.
  7. American Diabetes Association. Economic cost of diabetes in the US in 2002. Diabetes Care. 2003;26:917-32.
  8. Sekhar CY, Venu V, Jaganathan K, Selvi SR, Perumal P. Formulation and in-vitro evaluation of sustained release matrix tablets of glimepiride by using natural gums as release modifiers. J Global Trends in Pharm Sci. 2011;2(4):394-403.
  9. Lachman L, Lieberman HA. The theory and practice of industrial pharmacy. Special Indian edition. 2009:293-373.
  10. Remington. 20th edition. The Science and Practice of Pharmacy. Lippincott Williams & Wilkins, Delhi; 2002:903–914.
  11. Jain S, Yadav S, Patil U. Preparation and evaluation of sustained release matrix tablet of furosemide using natural polymers. Research Journal of Pharmacy and Technology. 2008;1(4):374-6.
  12. Augsburger LL, Zellhofer MJ. Tablet formulation. Encyclopedia of Pharmaceutical Technology. 2006:3641-52.
  13. Vazquez MJ, Perez-Marco, Gomez- Amoza JL, Martinez-Pacheco R, Souto C, Concheiro A. Influence of technological variables on drug release of drug from hydrophilic matrices. Drug Dev Ind Pharm. 1992;18:1355-75.
  14. Harland RS, Gazzaniga, A, Sangalli ME, Colombo P, Peppas NA. Drug/polymer matrix swelling and dissolution. Pharm. Res. 1998;5:488-94.
  15. Kannan S, Manivannan R, Ganesan K, Nishad PK, Kumar NS. Formulation and Evaluation of Sustained Release Tablets of Aceclofenac using Hydrophilic Matrix System. Int J PharmTech Res. 2010;2(3):1775-80.


  • There are currently no refbacks.

Copyright (c) 2017 Pharmaceutical and Biological Evaluations

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Creative Commons License


© Copyright 2018 - Pharmaceutical and Biological Evaluations