International Journal of Pharmacy and Pharmaceutical Sciences

Print ISSN: 2656-0097 | Online ISSN: 0975-1491 Vol 12, Issue 2, 2020

Original Article
FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE LOADED FLOATING
MICROSPHERES

SHIKHA KESHARVANI1*, PANKAJ KUMAR JAISWAL1, ALOK MUKERJEE1, AMIT KUMAR SINGH1
1United Institute of Pharmacy, Naini, Allahabad, Uttar Pradesh, India 211010
Email: shikhakeserwani55555@gmail.com
Received: 26 Jul 2019, Revised and Accepted: 16 Dec 2019
ABSTRACT
Objective: The main objective of this study was to develop and evaluate the eudragit and HPMC coated metformin hydrochloride floating
microspheres, in which HPMC helps in floating and eudragit as a coating material for a site-specific drug release in a controlled manner and the
active moiety metformin used as anti-hyperglycemic agent.
Methods: The floating microsphere was prepared by the solvent evaporation method incorporating metformin as a model drug. The prepared
floating microsphere were characterized for particle size, %yield, drug loading and entrapment efficiency, compatibility study, %buoyancy, surface
morphology and In vitro drug release and release kinetics.
Results: The result metformin loaded floating microsphere was successfully prepared and the particle size range from 397±23.22 to 595±15.82 µm,
the entrapment efficiency range from 83.49±1.33 to 60.02±1.65% and drug loading capacity range from 14.3±0.54 to 13.31±0.47% and %buoyancy
range from 85.67±0.58 to 80.67±1.15%. The FT-IR and X-RD analysis confirmed that no any interaction between drug and excipient, and surface
morphology confirmed those particles are sphere. The floating microsphere show maximum 96% drug release in pH 0.1N HCL and follow the
Korsmeyer peppas model of the super case-2 transport mechanism.
Conclusion: These results suggest that metformin loaded floating microspheres could be retain in stomach for long time and give site specific drug
release in controlled manner.
Keywords: Floating capability, Therapeutic Response, Eudragit and Metformin
© 2020 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijpps.2020v12i2.35099. Journal homepage: https://innovareacademics.in/journals/index.php/ijpps

INTRODUCTION porous hydrogel system [11], magnetic system, etc [12]. Here we are
developing lower density system that’s floating microsphere, is
Most preferred route for drug delivery is the oral route due to its prepared by solvent evaporation method incorporating metformin
patient compliance and easiness of ingestion and cost-effectiveness. as a model drug. The active moiety metformin is an anti-
Many different techniques have been developed like tablet capsule hyperglycemic agent that’s fast soluble in stomach pH so the drug
syrups etc for delivery of a significant amount of drug at a specific immediately released and not remains to specific site for long time.
site and time prearranged and systematic manner but this route has To overcome these problems, we prepare eudragit coated, HPMC
numerous physiological problems, like-easily bypass through GIT at and metformin hydrochloride loaded floating microspheres [13].
major absorption zone (stomach and upper part of intestine) due to The HPMC helps in floating that helps in long-time retention of
high density and low density retention time resulting incomplete microspheres into stomach and eudragit as a coating material to
drug release and low efficacy of drug unpredictable absorption due prevent the fast solubility of metformin hydrochloride in acidic pH
to degradation of drug by stomach acid and enzyme [1], hence the and give site specific drug release in a controlled manner. Then
site specific drug delivery for diabetic through oral route is also most metformin hydrochloride easily reduce the production from hepatic
challenging task for researchers. So these difficulties provoked the and glucose absorption from the intestine, and improved sensitivity
investigators to develop a DDS known as gastro retentive floating of insulin by increasing tangential uptake of glucose and its
microspheres which performs its actions i.e. its therapeutically utilization. In this process Metformin decreases blood glucose levels.
active plasma concentration of drug for prolonged period of time, by The recent study describes the various Gastro-retentive approaches
minimizing the dosing criteria and minimizing the fluctuations in which are newly developed into leading methodologies in the field of
plasma concentration of drug by the pharmacological effect of the site-specific orally controlled release drug delivery systems.
drug in a systemic and controlled way. After oral delivery of gastro
retentive floating microspheres, the drug reserved in to the stomach MATERIALS AND METHODS
and performs the action of drug release in a well-ordered manner, so
that the delivery of drug is continuous at its absorption sites in GIT Metformin hydrochloride was a gift sample from the Sun
(gastrointestinal tract) [2]. The floating systems are low-density Pharmaceutical Industries Ltd., Vadodara, India. HPMC was
systems that have sufficient buoyancy to float over the gastric procured from the LOBA Cheme Pvt. Ltd., Mumbai and the
content and remain buoyant the stomach without affecting the eudragitS100 was procured from the Central Drug House Pvt. Ltd.,
gastric emptying rate for a prolonged period of time which causes New Delhi. All the chemicals and solvent used in the study were of
the inadequate release of drug at the absorption site [3]. Over the analytical grade.
last minority decades, several gastro-retentive drug delivery Preparation of floating microspheres
systems being intended, including high-density systems that is
retain in the lower part of the stomach [4], lower density which Floating microspheres were prepared by emulsification (o/w)
cause buoyancy in gastric-juice [5, 6], mucoadhesive systems that solvent evaporation method using a varying concentration of
cause a bio-adhesion to stomach mucosa [7, 8], unfoldable, polymers (HPMC, Eudragit S100). The polymer solution was
extendible, or swellable systems which can restriction of the prepared by dissolving polymers (HPMC, EudragitS100) in different
emptying dosage forms through the pyloric sphincter [9, 10], super- ratio of the mixture of solvents (ethanol, dichloromethane) with
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vigorous shaking. The aqueous solution containing tween80 was microspheres. The formed microspheres were collected and washed
taken in another beaker. The polymer solution was then added with distilled water 2-3 times and air-dried for 24 h [14, 15]. The
manually dropwise into the aqueous solution through a syringe drug-loaded microspheres shown in fig. 1 were prepared by the
(needle size 22 gauges) under continuous stirring at 100 rpm. The solvent evaporation method according to the above-described
added droplets were kept dispersed in the aqueous solution for 30 method by varying concentration of polymers (HPMC, eudragit) and
min. to complete the reaction and to produce spherical rigid drug. The compositions of floating microsphere are given in table 1.

Table 1: Composition of the floating microsphere of each batch, HPMC-hydroxyl propyl methylcellulose, DCM-dichloromethane
Trial Formulation HPMC Eudragit S100 DCM+Ethanol Drug Aqueous phase containing 1% Tween 80
No. (mg) (mg) (ml)(1:3) (mg) (ml)
01 Formulation-1 400 100 20 0 150
02 Formulation-2 500 100 20 0 150
03 Formulation-3 600 100 20 0 150
04 Formulation-4 700 100 20 0 150
05 Formulation-5 800 100 20 0 150
06 Formulation-6 600 100 20 100 150
07 Formulation-7 700 100 20 100 150
08 Formulation-8 700 100 20 150 150
09 Formulation-9 700 100 20 175 150
10 Formulation10 700 100 20 200 150

Fig. 1: Preparation of floating microspheres

Particle size floating nature and the precipitated particles are taken out and dried
and weight. Percentage buoyancy was determined by the following
Particle size of the blank and metformin hydrochloride loaded formula [18].
microsphere was determined by optical microscopy method using a
compound microscope (Olympus India) equipped with ocular and Percentage buoyancy = 100
calibrated stage micrometers. After the calibration of an ocular
micrometer by placing the ocular lens after that the focusing on the Where-wf= Weight of floating particles, ws= Weight of settled
object to be measured and determine the size in ocular units, then particles
placing the samples on the slide and measuring the size of microspheres
[16]. Determination of drug content of microspheres

One ocular unit =

Division mm stage micrometer
100 µm/mm The 50 mg microspheres were dissolved in few ml of ethanol and
Ocular micrometer division dilute with 50 ml of 0.1N hydrochloric acid in a 100 ml volumetric
Percentage yield flask and mixture was shaken until a formulation was destructed.
The solution was passed through W. F. P (No. 41). Then diluted with
The percentage yield of the blank and metformin hydrochloride ethanol and evaluated by UV-VIS spectrophotometer (233λmax)
microspheres preparation was obtained by applying the mentioned using a UV-1800 Shimadzu spectrophotometer.
formula [17].
Weight of drug in the microsphere
Weight of the microspheres obtained
Loading drug content = 100
Total weight of microsphere
% Yield = × 100
Total weight of the drug and excipients
Drug entrapment efficiency
Percentage buoyancy
Entrapment efficiency of microspheres was determined by
The percentage buoyancy of the microspheres was calculated by the extraction of drug from the microspheres. In a typical procedure, 50
500 mg of the microspheres place in a USP mentioned type ІІ mg of dried microsphere were crushed in a mortar and pestle, and
instrument filled with 900 ml of 0.1 NHCL which consists of tween the fine microspheres dissolved in few ml of Ethanol and dilute with
80 with stirring for 12 h at 50 rpm. After 12 h the particles of 50 ml of 0.1N HCL for 24h. After 24h, the solution was passed

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through a 0.45μm filter and the conc. of the metformin In vitro drug release study
hydrochloride present in the filtrate was evaluated
spectrophotometrically at 233 nm using UV-Visible The In vitro drug release studies were performed by USP dissolution
Spectrophotometer (Shimadzu, UV-1800, Japan) with respect to 0.1N Test Apparatus Type 1 (Basket Type) at 100 rpm in 900 ml of
HCL as blank [19]. dissolution medium and at a temperature of 37 °C±0.5 °C. An
accurately weighed amount of prepared microspheres (equivalent to
Weight of drud in microspheres 100 mg) were used for the study. The test performed in 0.1N HCl as
Drug entrapment efficiency = ×100
Weight of the fed drug
dissolution media. After a time interval of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,
Micromeritic properties of microspheres 12 and 24 h, 5 ml of sample was withdrawn from dissolution media
and replaced by 5 ml of the fresh medium. The sample was passed
Prepared microspheres were evaluated for their micrometric through W. F. P. and assayed spectrophotometrically at 233 nm using a
properties such as as bulk density, tapped density, compressibility UV-Visible spectrophotometer (Shimadzu, UV-1800, Japan) [25, 26].
index, and angle of repose.
In vitro drug release kinetics
• Bulk density
To investigate the drug release mechanism from the microspheres,
Bulk density of microspheres was evaluated by the ratio of the in vitro drug release data was fitted to various kinetic models like
untapped microsphere weight and its volume it’s obtained by this zero order, first order, Higuchi equation, and Korsmeyer-Peppas
formula [20]. equation. By comparing the r values obtained, the best fit model was
selected [27-30].
Bulk density =
°
• Zero-order kinetics
Where M = Weight of microsphere sample, V ° = Apparent volume of
the microsphere Dissolution of the drug from the dosage forms that do not
disaggregate and release the drug slowly can be represented by the
• Tapped density following equation.
The tapped density was calculated by mechanical tapping of a Qt = Q0+K0t
graduated measuring cylinder which consists of the microspheres. It
is the ratio of the initial microsphere volume with tapped volume of Where, Qt is the amount of drug dissolved in time t, Q0 is the
microsphere (after tapping) [21]. Initial amount of drug in the solution and K0 is the zero-order
release rate constant. To study the release kinetics, data
Weight of microspheres obtained from the in vitro drug release studies were plotted as %
Tapped density =
Final tapped volume of the microspheres
CDR vs. Time.
• Compressibility index • First-order kinetics
The compressibility index is a tendency of microspheres to be This model has been used to describe the absorption or elimination
compressed. It’s calculated by this formula. of drugs. The release of the drug which followed first-order kinetics
CI = × 100 can be expressed by the following equation.

LogC = logC0-
Where-TD = Tapped Density, BD = Bulk Density 2.303

• Angle of repose Where C is the amount of drug release in time t, C0 is the amount
of drug in the solution and K is the first-order release rate
This property was evaluated by the maximum angle possible constant. To study the release kinetic data obtained from the in
between the surface of the pile of the microspheres and the vitro drug release studies were plotted as log % drug unreleased
horizontal plane; it’s obtained by the funnel in a fixed position. vs. Time.
θ = tan-1(h/r) • Higuchi model
Drug polymer compatibility study This model used to describe the release of water-soluble and low
water-soluble drugs from the solid or semisolid matrix system.
Drug-polymer interaction studies were carried out by using FT-IR
Mathematical expressions were obtained for drug particles
and XRD analysis.
dispersed in uniform matrix behaving as the diffusion media. The
• FTIR study mathematical expression of Higuchi model is as follows:

The FT-IR study of blank and drug-loaded formulations was Qt = KH. t1/2
performed to find any possible drug-polymer interaction using
Whereas Qt is the amount of drug release in time t and KH is the
Fourier Transform Infra-red spectrometer (Bruker Alpha, Germany)
Higuchi dissolution constant. To study the release kinetics, data
in the frequency range of 4000-400 cm-1 [22].
obtained from the in vitro drug release were plotted as % CDR vs
• XRD analysis Square root of time.

The effect of crystallinity of drug and excipient on formulation was • Korsmeyer-peppas model
evaluated by using XRD analysis. The XRD patterns of blank and
This model used to describe the release of drugs from the polymeric
drug-loaded microspheres were recorded using X-ray
system when the release mechanism is not well known or more than
Diffractometer (Rigaku-Ultima IV, Japan), using Cu radiation, a
one type of release phenomena could be involved. The equation of
voltage of 40 kV and a current of 30 mA. The scanning speed
the Korsmeyer-Peppas model is as follows:
employed was 2 °/min over the range of 10 ° to 90° diffraction angle
[23]. = Ktn
∞
Morphological characterization Mt
Where is the fraction of drug release, K is the release rate
M∞
The shape and size of the metformin hydrochloride-loaded constant, t is the release time and n is the release exponent
microsphere were assessed by SEM. The samples were prepared by
mounting the sample onto a metal stub with adhesive tape on both To study the release kinetics, data obtained from the in vitro drug
sides. Carbon coating was done in a high vacuum evaporator. Then release were plotted log % CDR vs. Time. Peppas used this n-value in
the process of scanning and taking images was done [24]. order to characterize different release mechanisms as given in table 2.

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Table 2: Different release mechanism

Diffusion release exponent (n) Overall drug diffusion mechanism Time-dependence of drug release rate (dMt/dt)
0.5 Fickian diffusion t- °.5
0.45<n = 0.89 Non-Fickian diffusion tn-1
0.89 Case II transport Zero order (time independent) release
Higher than 0.89 Super case II transport tn-t

RESULTS AND DISCUSSION be loaded with metformin hydrochloride in formulation F6 to F10. On

loading with 100 mg drug, F7 was found to have a better yield than F6
The metformin loaded lower density microsphere were prepared by but the particle size increase with drug concentration. On further
emulsification (o/w) solvent evaporation method according to the increasing the drug amount to 150 mg in F8 the % yield was found to
above-described method by varying concentration of polymers be increased. But afterward, the % yield was found to be constant with
(HPMC, eudragit) and metformin. increasing in the drug amount due to saturation of formulation.
Characterization of floating microspheres According to Patel B. et al., they also justified that increases the
polymer concentrations then increase the % yield as well as particle
% Yield and particle size size up to a level [31]. The maximum % yield was found to be of
formulation F8 as results shown in table 3.
The particle size of the optimized formulation was determined by the
optical microscopy. The % yield and particle size of the formulations % Buoyancy of the formulation
found to be b/w 70.5 to 86.8% and 397.73 to 628.27 µm. The
microspheres formulation F1, F2 was not formed completely only The % buoyancy depends on the density of HPMC and eudragit and
some particles appeared in solution. After filtration, the clumps of the drug in stomach contents 0.1 N HCL. The density of excipient and
microsphere adhere on the filter paper and not rigid and stable. It was drug was less hence microspheres float on 0.1 N HCL. The %
due to less concentration of HPMC. As the concentration of HPMC buoyancy of formulation F3 to F9 was found to be b/w 72.33 to
increased in formulation F3 and F4 the microspheres were formed 87.67%. The % buoyancy of blank F3 and F4 was high as compare to
with good yield and particle size values of F3 (72.9%, 397.73 µm) and other formulation due to the less concentration of both excipients.
F4 (81.1% 415.47 µm) respectively. On further increasing the HPMC And when gradually increase the concentration of HPMC with drug
concentration in formulation F5, the yield was found to be decreased the % buoyancy decrease. Formulation F7 and F8 were found to
but particle size was increase. Due to softness and aggregation of the have % buoyancy of 81.33 to 80.67%, respectively that was good as
microsphere with each other and adhere on filter paper again due to compared to other drug loaded formulation. The % buoyancy proves
the high concentration of HPMC. Finally F3 and F4 blank microsphere that the microsphere float in the stomach for a long time and worked
which ratio HPMC: Eudragit (7:1) were appropriate for rigid and as a gastro retentive drug delivery reservoirs [32]. The % buoyancy
stable microsphere so here F3 and F4 blank microsphere selected to shows in the table 3.

Table 3: %Yield, particle size and buoyancy of drug loaded microspheres

Formulation % Yield Particle size (µm) % Buoyancy
F3 72.9±0.56 397.73±23.22 85.67±0.58
F4 81.1±0.86 415.47±19.13 87.67±0.58
F5 70.5±0.65 628.27±30.72 72.33±1.53
F6 75.0±0.80 438.72±24.43 77.67±0.58
F7 84.4±0.66 476.27±11.61 81.33±1.53
F8 86.8±0.66 526.93±11.61 80.67±1.15
F9 79.2±1.21 567.47±24.43 75.33±0.58
F10 82.2±1.06 595.33±15.82 69.67±1.53
Data are presented as mean±SD (n = 3)

Drug loading and drug entrapment entrapment efficacy of formulations were determined by the direct
extraction method and the results are shown in table 4.
The % Drug loading and % entrapment efficiency of the formulation
were found to be b/w 11.10 to17.04% and 60.02 to 95.30% Micromeritic properties
respectively. Out of the five drug-loaded formulations (F6-F10), the
formulation F8 was found to have a maximum % drug loading All the micrometric properties were found in an acceptable range. The
(17.04%) and maximum % entrapment efficiency (95.30%). The % compressibility index of the formulations (F6, F7, F8, and F10) was
drug loading and % entrapment efficiency were found to be found range between (7.04 to 20.00 %) have excellent flow-ability and
decreased with an increase in the amount of drug to be loaded the formulation F9, found to have fair flow-ability. The angle of repose
beyond 150 mg (F8) i.e. F9, F10 due to the saturation of the of all the formulations range from (18.147 to 27.47%) showed
microspheres with the drug [33, 34]. The Drug loading and excellent flow property [35]. The results are shown in table 4.

Table 4: Drug loading, entrapment efficiency and micromeritic properties of drug-loaded microspheres
S. No. %drug loading %entrapment Bulk density Tapped density Compressibility index Angle of repose
efficiency (g/ml) (g/ml) (ɵ)
F6 14.30±0.54 83.49±1.33 0.75±0.01 0.86±0.01 12.79 18.15
F7 11.10±0.75 87.43±1.97 0.73±0.04 0.84±0.01 13.10 24.26
F8 17.04±0.43 95.30±0.49 0.66±0.02 0.71±0.02 7.04 21.80
F9 15.58±0.62 68.43±1.29 0.76±0.01 0.95±0.02 20.00 27.47
10 13.31±0.47 60.02±1.65 0.71±0.03 0.81±0.01 12.35 25.91
Data are presented as mean±SD (n = 3)

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Optimization of formulation because drug was absent in blank, and drug-loaded microspheres
exhibited all the characteristics of absorption bands as that of drug
The formulation F8 was optimized based on % yield, buoyancy, % metformin hydrochloride without any prominent changes and the
drug loading, % entrapment efficiency and micrometric properties FT-IR spectra shows that the drug has not gone through any kind of
because formulation F8 shows the good % yield (86.8%), % buoyancy
interactions with the excipient as well as formulation [36]. The FTIR
(80.67%), % drug loading (17.04%), % entrapment efficiency
spectra of drug and other excipient shown in fig. 2.
(95.30%) as compare to other formulation. Further studies i.e. FTIR
study, SEM, X-RD and drug release were performed on the optimized X-RD study
formulation (F8) that was finally optimized by the above parameters.
The effect of the crystallinity of the optimized formulation was
Drug polymer compatibility study recorded by using an X-ray diffractometer. From the study, it was
observed that Metformin hydrochloride showed sharp crystalline
FTIR study
peaks clearly visible at the position between 15-18 ° (2θ) shown in
FT-IR spectra were recorded to assess the compatibility of the pure fig.3 which shows the crystalline nature of the drug. The polymer
drug with other excipients present in the formulation. The FT-IR gave the broad spectrum peak that showed the amorphous nature of
spectrum of optimized microspheres formulation F8 was recorded the polymer. The diffract gram of the metformin-loaded microsphere
separately and compared with the spectrum of pure drug, HPMC, formulation (F8) showed diminished intensities of peak indicating
eudragit, blank formulation to verify the possible interaction that the drug was molecularly disbursed in the polymeric matrix or
between the constituent and the characteristic peaks. The main peak might have undergone amorphization during the preparation of the
of Metformin hydrochloride bands was N-H(stretching)-3365.04 cm- microspheres. The compatibility study confirmed that Metformin
1, N-(CH ) -3140.87 cm-1, C-N-930.38 cm-1and N-H(bending)-1622.37
3 2 hydrochloride was compatible with other excipient and doesn’t get
cm-1 was present in drug spectra but absent in the blank formulation al. tered during formulation of microsphere, was the show in fig. 3.

Fig. 2: FT-IR spectrum of HPMC, EudragitS100, Metformin hydrochloride, blank floating microspheres and optimized drug-loaded
microspheres (F8)

Fig. 3: X-RD of HPMC, eudragit, metformin hydrochloride, blank floating microspheres and optimized drug-loaded microspheres (F8)

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SEM (scanning electron microscopy) was found spherical with a rough surface and the microspheres
were solid without any porous on the surface. The agglomeration of
The shape and surface characteristics of metformin-loaded microspheres was not seen because of the rigid nature of
microsphere optimized formulation (F8) were determined by microspheres [37]. The SEM photograph of microspheres is shown
scanning electron microscope (SEM). The shape of the microsphere in fig. 4.

Fig. 4: SEM of the metformin hydrochloride loaded microspheres

In vitro drug release study formulations (F8) was performed by using USP Dissolution Test
Apparatus Type 1 (Basket Type) in the 0.1N HCl. The drug release
The in vitro drug release study demonstrated that metformin-loaded profile of optimized formulation (F8) was release the drug in a
microsphere optimized formulation (F8) showed maximum drug controlled manner for a long time that shows the formulation F8 was
release (96.48%) in the gastric pH 0.1N HCl up to 24 h and the work as a controlled drug delivery system and give high
sample was analyzed in triplicate. The in vitro study of optimized bioavailability [38]. The result of the release study is shown in fig. 5.

Fig. 5: Drug release graph of optimized formulation (F8) data points represented mean±SD (n=3)

In vitro drug release kinetics Korsmeyer-peppas model as the R2 value for the model was 0.971
which was very closer to 1, than the other R2 value of other models.
The data obtained from in vitro release study were fitted to various The drug release mechanism was of Super case II transport as the
kinetic equations to find out the mechanism of drug release from the release exponent, the drug get the release from the microsphere by
optimized drug loaded formulation (F8). The kinetic models used were erosion system, the ‘n’ value was found to be 1.490 which was greater
a zero-order equation, first-order equation, Higuchi model and than 1. The graphical representation of different kinetic models of in
Korsmeyer-Peppas model. Drug release kinetics was best fitted to the vitro drug release profile is shown in fig. 6 to 9 and table 5.

Table 5: Release kinetics of optimized formulation F8

Formulation code Zero order First order Higuchi model Korsmeyer-peppas
(R2) value (R2) value (R2) value (R2) value
F-8 0.879 0.953 0.903 0.971

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Fig. 6: Zero-order kinetics of optimized formulation (F8)

Fig. 7: First order kinetics of optimized formulation (F8)

Fig. 8: Korsmeyer-peppas model of optimized formulation (F8)

Fig. 9: Higuchi model of optimized formulation (F8)

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CONCLUSION 7. Shrma S, Pawar A. Low-density multiparticulate system for

pulsatile release of meloxicam. Int J Pharm 2006;313:150-8.
The HPMC and eudragit S100 blend microspheres loaded with 8. Santus G, Lazzarini G, Bottoni G, Sandefer EP, Page RC, Doll WJ,
metformin hydrochloride were formulated successfully by using a et al. An in vitro-in vivo investigation of oral bioadhesive
modified solvent evaporation method and optimized the F8
controlled release furosemide formulations. Eur J Pharm
formulation by different parameters like % yield, buoyancy, % drug
Biopharm 1997;44:39-52.
loading, % entrapment efficiency and micrometric properties. The %
9. Klausner EA, Lavy E, Friedman M, Hoffman A. Expandable
yield, % buoyancy, % drug loading and % entrapment efficiency was
found to be of optimized formulation F8 84.4%, 80.67%, 17.04% and gastro retentive dosage forms. J Controlled Release
95.30% respectively. The % yield was decreased with increasing the 2003;90:143-62.
drug concentration and the % buoyancy was affected by changing the 10. Deshpande AA, Shah N, Rhodes CT, Malik W. Development of a
ratio of polymer and drug. The % drug loading and % entrapment novel controlled-release system for gastric retention. Pharm
efficiency decreased with an increase in the amount of drug to be Res 1997;14:815-9.
loaded beyond 150 mg i.e. F9, F10 due to saturation of the 11. Park K. Enzyme-digestible swelling as platforms for longterm
microspheres with the drug. The FTIR spectrum of optimized oral drug delivery: synthesis and characterization. Biomaterials
formulation F8 showed that there was no chemical interaction and 1988;9:435.
drug was compatible with polymer. The sharp peak of Metformin 12. Fujimori J, Machida Y, Nagai T. Preparation of a magnetically-
hydrochloride was also appearing in optimized formulation F8, which responsive tablet and configuration of its gastric residence in
revealed the drug incorporate into the microspheres. The SEM study of beagle dogs. STP Pharma Sci 1994;4:425-30.
formulation F8 with nearly spherical shape and a rough surface 13. Kawashima Y, Niwa T, Takeuchi H, Hino T, Itoh Y. Hollow
without any pore. The formulation F8 release the 96% drug in 24 h microspheres for use as a floating controlled drug delivery
that shows the formulation F8 was work as a controlled drug delivery system in the stomach. J Pharm Sci 1992;81:135-40.
system. Drug release kinetics of F8 formulation was best fitted for the 14. Lee HJ, Park GT, Choi KH. Development of oral drug delivery
Korsmeyer-peppas model and the drug release mechanism was of system using floating microspheres. J Microencapsulation
super case-2 transport. In which drug release by erosion mechanism. 1999;16:715-29.
15. Obeidat WM, Price JC. Evaluation of enteric matrix
FUNDING
microspheres prepared by emulsion-solvent evaporation using
Nil scanning electron microscopy. J Microencap 2004;21:47-57.
16. Subrahmanyam CVS. Textbook of physical pharmaceutics. 2nd
AUTHORS CONTRIBUTIONS ed. Mumbai, India: Vallabh Publication; 2002.
Dr. Alok Mukerjee was a principle of my college United institute of 17. Patel A, Ray S, Thakur SR. In vitro evaluation and optimization
pharmacy Allahabad, and also my project guide. Mukerjee Sir gives of controlled release floating drug delivery system of
me a strong platform to perform this project. With the help of metformin hydrochloride. DARU 2006;14:57–64.
Mukerjee Sir my college provided funding for the study, statistical 18. Subham B, Gaurav C, Dilip KP. Investigation on cross-linking
support in analyzing data and for instrumental analysis. density for development of novel interpenetrating polymer
network (IPN) based formulation. J Sci Ind Res 2010;69:777-84.
Mr. Amit Kumar Singh worked as my co-guide. Singh Sir designed 19. Swamy SEK, Goud AB. Formulation and evaluation of sustained-
and conducted the study, data collection and data analysis and also release acelofenac microspheres. J Adv Pharm Sci 2012;2:155-66.
helped me for manuscript designing. 20. Shariff A, Manna PK, Paranjothy KL. Entrapment of
andrographolide in cross-linked alginate pellets: I. formulation
Mr. Pankaj Kumar Jaiswal worked as my colleague. He helped me in
and evaluation of associated release kinetics. Pakistan J Pharm
every step of my unit process and participated in the sequence
alignment and drafted the manuscript with me. He carried out the Sci 2007;20:1-9.
SEM and DSC analysis from the outside of college and helped me in 21. Ranjha NM, Khan H, Naseem S. Encapsulation and
the interpretation of data. And also give me moral support. characterization of controlled release flurbiprofen loaded
microspheres using beeswax as an encapsulating agent. J Mater
I am Shikha Kesharvani carried out all works related to this project Sci Mater Med 2010;21:1621-30.
with the help of my guide, co-guide and my colleague. And prepare 22. Patel R, Bhimani D, Patel J, Patel D. Solid-state characterization
all data that present in this manuscript and also design and sequence and dissolution properties of ezetimibe–cyclodextrins inclusion
alignment and drafted all things in this manuscript. complexes. J Incl Phenom Macrocyclic Chem 2008;60:241-51.
23. Mohamed MN, Khaleid MA, Mohamed AS. formulation and
All authors approved the final manuscript.
evaluation of extended-release metformin hydrochloride
CONFLICT OF INTERESTS beads. Int J Pharm Pharm Sci 2010;6:433-41.
24. Senthil SK, Jaykar B, Kavimani S. Formulation, characterization
The authors declare that they have no conflict of interest. and in vitro evaluation of floating microsphere containing
rabeprazole sodium. J Inn Tre Pharm Sci 2010;1:274-82.
REFERENCES
25. Bhardwaj P, Chaurasia D, Singh R, Swarup A. Development and
1. Rouge N, Buri P, Doelker E. Drug absorption sites in the characterization of novel site-specific hollow floating
gastrointestinal tract and dosage forms for site-specific microspheres bearing 5-fu for stomach targeting. Sci World J
delivery. Int J Pharma 1996;136:117-39. 2014. http://dx.doi.org/10.1155/2014/705259
2. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug 26. Kamel HA, Sokar SM, Gamal SS, Naggar FV. Preparation and
delivery system. Expert Opin Drug Delivery 2006;3:217-33. evaluation of ketoprofen floating oral delivery system. Int J
3. Iannucelli V, Coppi G, Bernabei MT, Camerorni R. Air Pharm 2001;220:13-21.
compartment multiple-unit system for prolonged gastric 27. Narasimha SDP, Murthay NL, Chowdhury P. Kinetic modelling
residence part-Iformulation study. Int J Pharm 1998;174:47-54. on drug release from controlled drug delivery system. Acta
4. Rouge N, Allemann E, Gex-Fabry M, Balant L, Cole ET, Buri P, et Pharm 2010;67:217-23.
al. Comparative pharmacokinetic study of a floating multiple- 28. Suleiman NN. The kinetics of drug release from ethylcellulose
unit capsule, a high-density multiple unit capsule and an solid dispersions. Drug Dev Ind Pharm 1985;11:2169-81.
immediate-release tablet containing 25 mg atenolol. Pharm 29. Simonelli DS, Higuchi W. Investigation of factors influencing
Acta Hel Betiae 1998;73:81-7. release of solid drug dispersed in inert matrices. J Pharm Sci
5. Streubel A, Siepmann J, Bodmeier R. Multiple units gastro 1965;54:1459-64.
retentive drug delivery: a new preparation method for low- 30. Higuchi T. Mechanism of sustained action medication.
density microparticles. J Microencapsule 2003;20:329-47. Theoretical analysis of the rate of release of solid drugs
6. Goole J, Vanderbist F, Aruighi K. Development and evaluation of dispersed in solid matrices. J Pharm Sci 1963;52:1145-9.
new multiple-unit levodopa sustained-release floating dosage 31. Patel B, Modi V, Patel K, Patel M. Preparation and evaluation of
forms. Int J Pharm 2007;334:35-41. ethyl cellulose microspheres prepared by an emulsification-

81
 Kesharvani et al.
Int J Pharm Pharm Sci, Vol 12, Issue 2, 74-82

solvent evaporation method. Int J Res Management Pharm 35. Ershad S, Sai KV, Kartheek U, Sandeep M, Prameela Rani K.
2012;1:82-91. Preparation and evaluation of floating microspheres of
32. Vaghani S, Vasanti S, Chaturvedi K, Satish CS. Stomach-specific ritonavir. J Pharm Pharm Sci 2014;3:5-11.
drug delivery of 5-fluorouracil using ethylcellulose floating 36. Mahaveer DK, Tejraj MA. Poly (vinyl alcohol) and poly (acrylic
microspheres. Pharm Dev Technol 2010;15:154–61. acid) sequential interpenetrating network pH-sensitive
33. Farooq U, Khan S, Nawaz S, Ranjha NM. Enhanced gastric microspheres for the delivery of diclofenac sodium to the
retention and drug release via the development of novel intestine. J Controlled Release 2004;96:9–20.
floating microspheres based on Eudragit E100 and 37. Sharma M. In vitro and in vivo evaluation of repaglinide loaded
polycaprolactone: synthesis and in vitro evaluation. Des floating microspheres prepared from different viscosity grades
Monomers Polym 2017;20:419-33. of HPMC polymer. Saudi Pharm J 2015. Doi:10.1016/
34. Choudhury PM, Kar M, Chauhan SC. Cellulose acetate j.jsps.2015.02.013
microspheres as floating depot systems to increase gastric 38. Dubey M, Kesharwani P, Tiwari A, Chandel R. Formulation and
retention of antidiabetic drug: formulation, characterization and evaluation of floating microsphere containing an anti-diabetic
in vitro–in vivo evaluation. Drug Dev Ind Pharm 2008;34:349–54. drug. Int J Pharm Chem Sci 2012;1:1038-47.

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