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Research Article CODEN: IJPRNK IMPACT FACTOR : 4.278 ISSN: 2277-8713 Asija R, IJPRBS, 2014; Volume 3(4): 89-116 IJPRBS
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FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERE OF ESOMEPRAZOLE
ASIJA R, SHARMA D, KUMAWAT J Maharishi Arvind Institute of Pharmacy, Jaipur.
Accepted Date: 28/06/2014; Published Date: 27/08/2014
Abstract: The gastro retentive drug delivery systems can be retained in the gastrointestinal track for longer period of time and improve the oral bioavailability of drug. In the present research work, mucoadhesive microspheres of esomeprazole were prepared and evaluated. The mucoadhesive microspheres were prepared by solvent evaporation method. Coating of microsphere is done by method as described by Gopferich Achim et al. The surface morphological characteristics of mucoadhesive microspheres were investigated using scanning electron microscopy. The scanning electron microscopy of formulation code F14 reveals that the microspheres were spherical, discrete with rough texture. The highest percentage mucoadhesion was found 14% in formulation F14. By, above results it was concluded that formulation code F14 showed reproducible results, with good Mucoadhesive properties and good surface morphology.
Keywords: Mucoadhesive, Microsphere, Esomeprazole, Gastro Retentive Drug Delivery.
INTERNATIONAL JOURNAL OF
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Corresponding Author: DR. RAJESH ASIJA
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Asija R, Sharma D, Kumawat J; IJPRBS, 2014; Volume 3(4): 89-116
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INTRODUCTION
Several approaches have been studied to increase the residence time of the dosage form
including floating drug delivery system (DDS), swelling and expending drug delivery system,
mucoadhesive DDS and high density DDS. Various gastrointestinal mucoadhesive dosage forms,
such as bilayered tablets, microspheres, have been thoroughly prepared and reported by
several research groups1. Among the number of approaches, mucoadhesive drug delivery
system is one of the promising delivery system in which drug delivery system adheres to the
mucous layer of stomach and thus remains in stomach for longer period of time2.
Mucoadhesion is defined as a state in which two components, of which one is of biological
origin, are held together for extended periods of time by the help of interfacial forces.
Generally speaking, bioadhesion is a term, which broadly includes adhesive interactions with
any biological or biologically derived substance, and mucoadhesion is used when the bond is
formed with a mucosal surface, while the term cytoadhesive implies adhesion to cells. Thus
Mucoadhesive drug delivery systems are type of gastro retentive drug delivery systems. 3, 4, 5
In the development of oral controlled-release dosage forms, considerable benefits may ensue
from the use of bioadhesive or mucoadhesive polymers providing relatively short-term
adhesion between the drug delivery system and the mucus or epithelial cell surface of the
gastrointestinal tract. So Binding will therefore involve secondary forces, like hydrogen bonds
or Vander Waals forces. Mucoadhesives may, therefore, be regarded as a specific class of
bioadhesives.6 When mucoadhesive polymers are utilized, the residence time of dosage forms
on the mucosa can be significantly prolonged, allowing a sustained drug release at a given
target site.7
Microspheres may be defined as solid, spherical particles that range in size 1-1000 μm and
which are made up of polymeric, waxy or other protective materials such as biodegradable
synthetic polymers and modified natural products such as polysaccharides, gums, proteins, fats
and waxes. For example, natural polymers include albumin and gelatin. Similarly the synthetic
polymers include polylactic acid and polyglycolic acid. Microspheres are small in size and
possess large surface to volume ratio. The lower sized microspheres have colloidal properties.
The interfacial properties of microspheres are extremely important, often dictating their
activity.8,9
Esomeprazole is Anti-Ulcer Agent, Proton-pump Inhibitors and Antihistamines. It is absorbed
completely (90%) after oral administration and the protein binding of esomeprazole is 97%.
Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme
system and approximately 80% of an oral dose of esomeprazole is excreted as inactive
metabolites in the urine and the remainder is found as inactive metabolites in the feces.
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MATERIALS & METHODS:
Materials:
The following ingredients are used in present investigation:
Table 1: List of ingredients used
Ingredients Manufacture name
Esomeprazole magnesium trihydrate Heliox pharma
Ethyl cellulose Cental drug house (P) Ltd.
Hpmc k100m Cental drug house (P) Ltd.
Ethanol Changsu yangyuan chemical, china
Dichloromethane Finar chemical Ltd., Ahemdabad
Light paraffin liquid Finar chemical Ltd., Ahemdabad
Petroleum ether Thomas beaker
Cellulose acetate phthalate Cental drug house (P) Ltd.
Methods:
Preparation of mucoadhesive microsphere10-13:
The mucoadhesive microspheres were prepared by solvent evaporation method. Ethanol and
dichloromethane was taken in 1:1 ratio in 10 ml beaker. Weighed amount of HPMC K100M in
the above solution and dissolved completely. Then weighed amount of ethyl cellulose added
into the beaker and dissolved completely, and then weighed amount of esomeprazole was
added and stirred with glass rod and dissolved. 25 ml of light liquid paraffin was taken in 100ml
beaker and stirred by stirrer at 1000 rpm. Then the drug-polymer solution was added drop wise
drop in LPL with the help of syringe (21 no needle) and starring continued for 1 hr. Then after 1
hr the prepared microspheres were separated with the help of Whattman grade filter, washed
several time with petroleum ether. Then the microspheres were dried at room temperature for
12 hrs. The microspheres are prepared at different concentration of ethyl cellulose, HPMC
K100M, ethanol, dichloromethane and different temperature range39.
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Coating of mucoadhesive microspheres14-17
Coating of microshere is done by method as described by Gopferich Achim et al. 100 mg of
dried core microspheres were directly dispersed by vortexing for 5sec into 1 ml of ethanol and
acetone (1:1 ratio) solution containing 20mg coating polymer (cellulose acetate phthalate). The
coated microspheres were filtered by whattman grade filter paper and dried.
Table 2: Formulae for first batch of mucoadhesive microsphere of esomeprazole
Formulation
code
Drug
(mg)
Ethyl
cellulose
(mg)
HPMC
K100M
(mg)
Ethanol
(ml)
Dichloromethane
(ml)
Temperature
(°C)
F1 30 15 15 1.2 1.2 37
F2 30 30 30 1.2 1.2 37
F3 30 60 30 1.2 1.2 37
F4 30 30 60 1.2 1.2 37
F5 30 30 90 1.2 1.2 37
F6 30 90 30 1.2 1.2 37
Table 3: Formulae for second batch of mucoadhesive microsphere of esomeprazole
Formulation
code
Drug
(mg)
Ethyl
cellulose
(mg)
HPMC
K100M
(mg)
Ethanol
(ml)
Dichloromethane
(ml)
Temperature
(°C)
F7 30 30 30 0.5 0.5 37
F8 30 30 30 1 1 37
F9 30 30 30 1.2 1.2 37
F10 30 30 30 1.4 1.4 37
F11 30 30 30 1.5 1.5 37
F12 30 30 30 2 2 37
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Table 4: Formulae for third batch of mucoadhesive microsphere of esomeprazole
Formulation
code
Drug
(mg)
Ethyl
cellulose
(mg)
HPMC
K100M
(mg)
Ethanol
(ml)
Dichloromethane
(ml)
Temperature
(°C)
F13 30 30 30 1.2 1.2 35
F14 30 30 30 1.2 1.2 37
F15 30 30 30 1.2 1.2 40
F16 30 30 30 1.2 1.2 43
EVALUATION OF MUCOADHESIVE MICROSPHERES
1. Identification study of drug18-21
A. Physical description:
The procured sample of drug was characterized for its physical characteristics like appearance
and odour.
B. melting point:
The normal melting point of a solid can be defined as the temperature at which the solid and
liquid are in equilibrium at a total pressure of 1 atmosphere. Experimentally, melting point is
actually recorded as the ‘range of temperatures’ in which the first crystal starts to melt until the
temperature at which the last crystal just disappears. Melting point was determined with the
help of melting point apparatus made by prefit India.
For the determination of melting point a capillary tube was taken. One end of capillary tube
was sealed by heating the one end with the help of candle. The drug was inserted from another
end of capillaty tube. The capillary tube and a thermometer inserted in meting point apparatus.
The melting point range was determined.
2. Solubility analysis22, 23
The solubility of esomeprazole was determined in various solvents. The study was performed
using shake flask method. Saturated solution of esomeprazole was prepared in respective
solvent media and stirred for 24 hours. The solution was then centrifuged for 15 min over
10,000 rpm and filtered through whatmann filter paper (#44). The concentration of
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esomeprazole was determined using UV-visible spectrophotometer (UV-1800, Shimadzu
corporation) against methanol as blank.
3. Partition Coefficient11, 24, 25
Partition coefficient is a measurement of drug’s lipophillicity and its ability to cross cell
membrane. Partition coefficient of esomeprazole was determined at 37 ± 0.5 °C by taking 10 ml
of 1-octanol and 10ml distill water in separating funnel.10 mg of drug was taken in separating
funnel. Separating funnel was shaken for 10 min. After shaking, the system remained
undisturbed for half an hour and stand for 24 hrs. After 24 hrs two layers were separated
through separating funnel and the amount of esomeprazole solubilized in octanol was
determined by measuring the absorbance at 301 nm against methanol through double beam
UV/Vis spectrophotometer.
Subtracting this amount from the total amount of drug gave the amount of drug present in the
aqueous phase. Partition co-efficient was determined as ratios of amount of drug in octanol to
the amount of drug in distill water and its logarithm value was taken for log P.
Concentration of drug in non-aqueous phase KO/W = ––––––––––––––––––––––––––––––––––––––– Concentration of drug in aqueous phase
4. Determination of absorption maxima of Esomeprazole26, 27
A. Determination of absorption maxima of in methanol
10 mg accurately weighed drug was transferred into a 100 ml volumetric flask and dissolved in
sufficient quantity of methanol. The volume was made up to 100 ml with the solvent. 1 ml of
the above solution was diluted up to 10 ml with same methanol (10 µg/ml) and was scanned
under UV-Visible Spectroscope (UV 1800, Shimadzu corporation) for determination of λmax
(absorption maxima). The same solution was reread three times. The above procedure was
repeated for one more solution of same concentration. All the readings gave same value of
λmax.
B. Determination of absorption maxima of esomeprazole in pH 6.8 buffer
10 mg accurately weighed drug was transferred into a 100 ml volumetric flask and dissolved in
sufficient quantity of PH 6.8 buffer. The volume was made up to 100 ml with the solvent. 1 ml
of the above solution was diluted up to 10 ml with same PH 6.8 buffer (10 µg/ml) and was
scanned under UV-Visible Spectroscope (UV 1800, Shimadzu corporation) for determination of
λmax(absorption maxima). The same solution was reread three times. The above procedure was
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repeated for one more solution of same concentration. All the readings gave same value of
λmax.
C. Determination of absorption maxima of in 1N NaOH
10 mg accurately weighed drug was transferred into a 100 ml volumetric flask and dissolved in
sufficient quantity of 1N NaOH. The volume was made up to 100 ml with the solvent. 1 ml of
the above solution was diluted up to 10 ml with same 1N NaOH (10 µg/ml) and was scanned
under UV-Visible Spectroscope (UV 1800, Shimadzu corporation) for determination of
λmax(absorption maxima). The same solution was reread three times. The above procedure was
repeated for one more solution of same concentration. All the readings gave same value of
λmax.
D. Determination of absorption maxima of esomeprazole in 0.1 N HCl
10 mg accurately weighed drug was transferred into a 100 ml volumetric flask and dissolved in
sufficient quantity of 0.1 N HCl. The volume was made up to 100 ml with the solvent. 1 ml of
the above solution was diluted up to 10 ml with same 0.1 N HCl (10 µg/ml) and was scanned
under UV-Visible Spectroscope (UV 1800, Shimadzu corporation) for determination of
λmax(absorption maxima). The same solution was reread three times. The above procedure was
repeated for one more solution of same concentration. All the readings gave same value of
λmax.
5. preparation of calibration curves of esomeprazole7, 28, 29
For the determination of the content of esomeprazole, standard plots of the drug were
prepared in methanol, 1NNaOH, pH 6.8 buffer, 0.1 N HCl in a suitable concentration range.
Stock solutions of the esomeprazole in the respective solvents having concentration of
100µg/ml were prepared and diluted serially to attain a concentration range between 2-
28µg/ml. These were analyzed spectrophotometrically at 301, 305, 300, 278 nm respectively
using UV spectrophotometer.
6. Determination of percent yield of microspheres30, 31
Thoroughly dried microspheres were collected and weighed accurately. The percentage yield
was then calculated using the formula given below-
% yield = Mass of microspheres obtained / Total weight of drug and polymer used × 100
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7. Determination of Entrapment Efficiency32, 33
The entrapment efficiency of the microspheres or the percent entrapment can be determined
by allowing washed microspheres to lyse. The lysate is then subjected to the determination of
active constituents as per monograph requirement. The percent encapsulation efficiency is
calculated using following equation-
% Entrapment = Actual content / Theoretical content x 100
8. Particle size analysis of microsphere9, 34, 35
Particle size analysis of drug loaded microspheres was determined by optical microscopic
method using a compound microscope. At least 100 microspheres were analyzed for each
preparation and the mean particle size was determined by using Edmondson’s equation
D mean = Σnd/Σn
Where n= number of microspheres observed and d= mean size range
9. Scanning electron microscopy35,36,37
A scanning electron microscope was used to characterize the surface topography of the
microspheres after gold coating. A scanning electron photomicrograph of drug-loaded
microspheres was taken. A small amount of microspheres was spread on glass stub. Afterwards,
the stub containing the sample was placed in the scanning electron microscope (JEOL, JSM-
6360) chamber. The scanning electron photomicrograph was taken at the acceleration voltage
of 10 kV, chamber pressure of 0.6 mm Hg, original magnification 500.
10. Flow properties12,38
It is defined as the maximum angle possible between the surface of pile of the powder and the
horizontal plane. The angle of repose was determined by the funnel method. A funnel was
secured with its tip at a given height (h), above a flat horizontal surface on which a graph paper
was placed. Microspheres were carefully poured through a funnel until the apex of the conical
pile just touches the tip of funnel. The angle of repose was then calculated using the formula.
θ = tan-1(h/r)
Where, θ = angle of repose, h = height of pile, r = radius of the base of the pile.
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11. In vitro mucoadhesion test31, 34
In the present study, the eggshell membrane was used to substitute the animal stomach
mucosa in the mucoadhesion evaluation of microspheres, based on the similarity between the
eggshell membrane and the stomach mucus with respect to its composition and thickness. The
good correlation between in vitro data from the eggshell membrane and in vivo mucoadhesion
studies demonstrated the potential of the eggshell membrane as substitute for the gastric
mucosa. The eggshell membranes were obtained from fresh chicken eggs. After emptying the
egg of its content, the external shell was removed, and the underlying membrane was isolated.
A piece of egg membrane was tied on to a glass slide. Approximately 50 microspheres were
spread onto the wet membrane and the prepared slide was hung on one the groves of a USP
tablet disintegrating test apparatus. The disintegrating test apparatus was operated such that
membrane specimen was given regular up and down movements in a beaker containing the
simulated gastric fluid USP (pH 6.8). At the end of 1, 5 and 10h, the microspheres still adhering
onto the membrane was counted.
12. In vitro release studies38, 39
Coated microsphere equivalent to 40 mg of esomeprazole magnesium (formulation F14) were
taken and the release rate of drug from coated microsphere was determined using USP type 1
apparatus. The microspheres were taken in basket. Then the basket was immersed in pH 1.2
HCl buffer for 2hr followed by phosphate buffer of pH 6.8 for 10 hr maintained at 37°C± 0.5°C
and was rotated at the speed of 100 rpm. Sample aliquots of 5ml were withdrawn at every hour
up to 12hrs and estimated for its drug content using UV spectroscopy at 300 nm.
RESULT AND DISCUSSION:
Identification of drug:
Physical description: The drug was found yellowish in colour and odourless.
Melting point: Melting point was found 178-183°C.
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FT-IR studies
FT-IR of drug
Figure 1: FT-IR Spectrum of Esomeprazole
FT-IR of HPMC K 100 M
Figure 2: FT-IR Spectrum of HPMC K 100 M
FT-IR of ethyl cellulose
Figure 3: FT-IR of ethyl cellulose
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FT-IR data of drug and polymer
Figure 4: FT-IR data of drug and polymer
FT-IR of Drug and polymer
Table 5: Interpretation of FT-IR spectra
Functional group Reference
peak
Observed peak of
drug
Observed peak of
ethyl cellulose
Observed peak of
HPMC K100M
Observed peak of
drug and polymer
mixture
C-H (hetero-
aromatic ring)
3080-3000 3070.46 - - 3068.53
N-H 3500-3220 3413.77 - -- 3421.48
C-S 700-600 636.47, 661.54,
696.25
- - 636.47, 661.54,
696.25
S=O 1080-1030 1076.21 - - 1076.21
CH3-O-Ar 1275-1200 1226.64, 1272.93 - - 1226.64, 1251.72,
1272.93
C=C(hetero-
aromatic ring)
1600-1430 1434.94, 1477.37,
1569.95, 1591.16
- - 1434.94, 1477.37,
1569.95, 1591.16
C=N (hetero-
aromatic ring)
1600-1430 1434.94, 1477.37,
1569.95, 1591.16
- - 1434.94, 1477.37,
1569.95, 1591.16
Aryl akyl ether 1275-1200 - 1234.36 1265.22 1226.64, 1251.72,
1272.93
C-O-C 1150-1085 - 1110.92 1116.71 1114.78
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Identification of drug and polymer:
The drug and polymer are identified by FT-IR as the observed peak of drug and polymer was
matched with reference peak of drug and polymer respectively.
Drug and polymer compatibility study:
The compatibility between drug and polymer was determined by FT-IR. The position of peak in
FT-IR spectra of pure drug and polymers were compared with those in FT-IR spectra of drug-
polymer mixture. No disappearance or significant shift in the peak position of drug and polymer
in the spectra was observed, which proves that the drug and polymers used for the study are
compatible.
Solubility study
The solubility study of esomeprazole in different solvent suggests that the drug is maximum
soluble in methanol and minimum soluble in light liquid paraffin than other solvent.
Descending order of solubility in different solvents-
Methanol > Ethanol > pH 7.4 buffer > Choloform > Acetone > Tween 80 > Span 80 > n-haxane >
light liquid paraffin.
Table 6: Solubility of esomeprazole
S.No. Solvent Solubility (mg/ml)
1 Methanol 247.027027
2 Ethanol 230.2702703
3 Acetone 53.24324324
4 Light liquid paraffin 0.190540541
5 n-haxane 0.202702703
6 Choloform 99.45945946
7 Span 80 4.243243243
8 Tween 80 8.324324324
9 pH 7.4 buffer 103.030303
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Partition Coefficient:
The partition coefficient of esomeprazole between octanol and water was found to be 4.52 and
log P value was 0.655368, which showed that drug is lipophillic in nature.
Determination of absorption maxima of esomeprazole:
The absorption maxima of esomeprazole was found 301nm in methanol, 300 nm pH 6.8 buffer,
305nm in 1N NaOH.
Calibration curve of esomeprazole in different solvents:
Calibration curve of esomeprazole in methanol was prepared and R² value was found 0.9885.
Calibration curve of esomeprazole in pH 6.8 buffer was prepared and R² value was found
0.9968.
Calibration curve of esomeprazole in 1N NaOH was prepared and R² value was found 0.9844.
Calibration curve of esomeprazole in 0.1 N HCl was prepared and R² value was found 0.993.
Determination of absorption maxima of in methanol:
Table 7: Determination of absorption maxima of esomeprazole in methanol
Figure 5: Determination of absorption maxima of esomeprazole in methanol
Solution ID Concentration Trial 1 Trial 2 Trial 3
λmax Abs λmax Abs λmax Abs
Solution 1 10 µg/ml 301 0.392 301 0..392 301 0.392
Solution 2 10 µg/ml 301 0.392 301 0.392 301 0.392
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Table 8: Determination of absorption maxima of esomeprazole in pH 6.8 buffer
Figure 6: Determination of absorption maxima of esomeprazole in pH 6.8 buffer
Table 9: Determination of absorption maxima of esomeprazole in 1N NaOH
Table 10: Determination of absorption maxima of esomeprazole in 0.1N HCl
Solution ID Concentration Trial 1 Trial 2 Trial 3
λmax Abs λmax Abs λmax Abs Solution 1 10 µg/ml 300 0.361 300 0..361 301 0.361 Solution 2 10 µg/ml 300 0.361 300 0.361 301 0.361
Solution ID Concentration Trial 1 Trial 2 Trial 3
λmax Abs λmax Abs λmax Abs Solution 1 10 µg/ml 305 0.473 305 0.473 305 0.473 Solution 2 10 µg/ml 305 0.473 305 0.473 305 0.473
Solution ID Concentration Trial 1 Trial 2 Trial 3
λmax Abs λmax Abs λmax Abs Solution 1 10 µg/ml 278 0..478 278 0.478 278 0.478 Solution 2 10 µg/ml 278 0.478 278 0.478 278 0.478
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Figure 7: Determination of absorption maxima of esomeprazole in 0.1 N HCl
Calibration curve of esomeprazole in Methanol
Table 11: Absorbance data for calibration curve of esomeprazole in methanol
S.no Concentration (µg/ml) Absorbance
1 1 0.056 2 2 0.1 3 4 0.135 4 6 0.232 5 8 0.309 6 10 0.392 7 12 0.475 8 14 0.558 9 16 0.641 10 18 0.724 11 20 0.807 12 22 0.890 13 24 0.973
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Figure 8: Calibration curve of esomeprazole in methanol
Calibration curve of esomeprazole in pH 6.8 buffer
Table 12: Absorbance data for calibration curve of esomeprazole in pH 6.8 buffer
S.no. Concentration µg/ml Absorbance
1 1 0.062 2 2 0.091 3 4 0.146 4 6 0.202 5 8 0.309 6 10 0.361 7 12 0.432 8 14 0.492 9 16 0.560 10 18 0.603 11 20 0.680 12 22 0.757 13 24 0.834 14 26 0.911 15 28 0.988
y = 0.0371x + 0.0124 R² = 0.9885
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0 5 10 15
Series1
Linear (Series1)
Std. curve in methanol
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Figure 9: Calibration curve of esomeprazole in pH 6.8 buffer
Calibration curve of esomeprazole in 1N NaOH
Figure 10: Calibration curve of esomeprazole in 1N NaOH
y = 0.033x + 0.0255 R² = 0.9968
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0 5 10 15 20 25
Series1
Linear (Series1)
Std. curve in PH 6.8 buffer
y = 0.0463x + 0.0186 R² = 0.9844
0
0.2
0.4
0.6
0.8
1
1.2
0 5 10 15 20 25
std. curve in NaOH
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Table 13: Absorbance data for calibration curve of esomeprazole in 1N NaOH
S.no. Concentration ( µg/ml) Absorbance
1 2 0.115 2 4 0.197 3 6 0.316 4 8 0.408 5 10 0.473 6 12 0.553 7 14 0.676 8 16 0.674 9 18 0.892 10 20 0.975
Calibration curve of esomeprazole in 0.1 N HCl
Figure 11: Calibration curve of esomeprazole in 0.1 N HCl
Table 14: Absorbance data for calibration curve of esomeprazole in 0.1 N HCl
S.no. Concentration ( µg/ml) Absorbance
1 2 0.092 2 4 0.163 3 6 0.263 4 8 0..343 5 10 0..487 6 12 0.520
y = 0.0392x + 0.0311 R² = 0.9935
0
0.2
0.4
0.6
0.8
1
1.2
0 5 10 15 20 25 30
Series1
Linear (Series1)
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7 14 0.570 8 16 0.651 9 18 0.738 10 20 0.809 11 22 0.883 12 24 0.962
Determination of percent yield of microspheres
Table 15: Percent yield of microspheres
S.No. Formulation code % production yield
1 F1 68.33 2 F2 65 3 F3 69.16 4 F4 59.58 5 F5 74 6 F6 81.86 7 F7 49.55 8 F8 85 9 F9 65 10 F10 89.55 11 F11 71.77 12 F12 96.11 13 F13 65 14 F14 96.88 15 F15 86.22 16 F16 76.88
In first batch highest percentage yield was found in formulation code F6. In second batch the
highest percentage yield was found in formulation code F12. In third batch the highest
percentage yield was found in formulation code F14.
Determination of Entrapment Efficiency
Table 16: Entrapment Efficiency
Formulation code
Theotical drug content (mg)
Practical drug content (mg) % Drug content
F1 7.31 5.23 71.54 F2 5.12 5.11 99.80 F3 3.61 1.6652 46.12 F4 4.19 1.52 36.42 F5 2.70 1.24 46.03 F6 2.44 1.52 62.48
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F7 6.72 2.891 43.02 F8 3.921 2.089 53.27 F9 5.12 5.11 99.80 F10 3.35 1.96 58.77 F11 4.64 2.86 61.83 F12 3.46 2.36 68.31 F13 5.12 5.11 99.80 F14 3.44 3.21 93.51 F15 3.86 2.19 56.80 F16 4.33 2.32 53.65
In first batch the highest entrapment efficiency was found in formulation code F2. In second
batch the highest entrapment efficiency was found in formulation code F9. In third batch the
highest entrapment efficiency was found in formulation code F13.
Particle size analysis of microsphere
Table 17: Particle size analysis of microsphere
S.No. Mean particle size (µm)
F2 F9 F14 1 32.5 24 32.4
The mean particle size of microsphere was found 32.5 µm, 24 µm, 32.5 µm of formulation F2,
F9, F14 respectively.
Scanning electron microscopy
The scanning electron microscopy of formulation code F14 reveals that the microspheres were
spherical, discrete with rough texture.
Figure 12: Scanning electron microscopy of formulation F14
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In vitro mucoadhesion test
Table 18: In vitro mucoadhesion test
S.No. Time (Hr) No. of microsphere adhere
% Mucodhesion
F2
F9
F14
F2
F9
F14
1 0 50 50 50 100 100 100 2 5 35 32 45 70 64 90 3 10 4 2 7 8 4 14
The table shows that some of microspheres were adhere to the membrane even after 10hrs.
The highest percentage mucoadhesion was found 14% in formulation F14.
Flow properties
Table 19: Angle of repose of formulation F2
S.No. Height of pile (cm) Radius of the base of the pile
(cm)
Angle of
repose
1 h 1=0.5 Average
height
=0.5cm
r 1 = 0.9 Average
radius
=0.9cm
=290 2 h 2=0.5 r 2= 0.9
3 H 3=0.5 r 3 = 0.9
Table 20: Angle of repose of formulation F9
S.No. Height of pile (cm) Radius of the base of the pile
(cm)
Angle of
repose
1 h 1=0.7 Average
height
=0.633cm
r 1 = 1.1 Average
radius
=0.933cm
=34.150 2 h 2=0.4 r 2= 0.8
3 H 3=0.8 r 3 = 0.9
Table 21: Angle of repose of formulation F14
S.No. Height of pile (cm) Radius of the base of the pile
(cm)
Angle of
repose
1 h 1=0.7 Average
height
=0.66cm
r 1 = 0.9 Average
radius
=0.9cm
=36.250 2 h 2=0.6 r 2= 0.9
3 H 3=0.7 r 3 = 0.9
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Angle of repose less than or equal to 40° indicates free flowing properties of the microspheres.
However angle of repose greater than 40° indicates poor flow of material. It can be observed
from table that the angle of repose for various batches of the microspheres is found to be less
than 40°, it indicates good flow properties of the microspheres.
In vitro release studies
Table 23: Percentage cumulative drug release
S.No. Time (hrs) Percentage cumulative drug release
1 0 0
2 1 18.46154
3 2 27.21795
4 3 39.79866
5 4 46.15472
6 5 55.27214
7 6 64.43881
8 7 72.9729
9 8 80.87063
10 9 84.0373
11 10 87.90093
12 11 88.95367
13 12 89.96212
Figure 13: percentage cumulative drug release
0 10 20 30 40 50 60 70 80 90
100
0 5 10 15
Time (hrs)
% c
um
ula
tive
dru
g re
leas
e
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Drug release kinetics
1. Zero order
Fig 14: Zero order
2. First order
Fig 15- first order
y = 7.444x + 13.493 R² = 0.9431
0
20
40
60
80
100
120
0 5 10 15
Series1
Linear (Series1)
per
cen
tage
cu
mu
lati
ve d
rug
rele
ase
time (hrs)
y = -0.0895x + 2.0395 R² = 0.9867
0
0.5
1
1.5
2
2.5
0 5 10 15
Series1
Linear (Series1)
time (hrs)
log
per
cen
tage
dru
g re
mai
nin
g
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3. Higuchi model
Fig 16- higuchi model
4. koresmayer peppas model
Fig 17- koresmayer peppas model
y = 29.293x - 7.7507 R² = 0.9783
-20
0
20
40
60
80
100
0 1 2 3 4
Series1
Linear (Series1)
square root of time
per
cen
tage
cu
mu
lati
ve d
rug
rele
ase
y = 1.1855x + 0.8284 R² = 0.6902
0
0.5
1
1.5
2
2.5
0 0.5 1 1.5
Series1
Linear (Series1)
log time
log
% c
um
ula
tive
dru
g re
leas
e
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Table 24: Drug release kinetics
S.No. Zero order higuchi First order Peppas
1 0.943 0.978 0.986 0.690
The value of r2 (0.986) was found to be highest for the First order model, which also indicates
that the test product follows First order release kinetics. The n value was found 0.828. Values of
n between 0.45 and 0.89 can be regarded as an indicator of both phenomena (drug diffusion in
the hydrated matrix and the polymer relaxation) commonly called anomalous transport.
CONCLUSION:
Ethycellulose was used as matrix polymer in which drug was dispersed because of its
hydrophobic characteristic. Hydroxy propyl methyl cellulose (K 100M) was used as
Mucoadhesive polymer. By observing above all evaluation parameters, it was concluded that
formulation code F14 showed reproducible results, with good Mucoadhesive properties and
good surface morphology. The formulation follows first order kintecs and anomalous transport.
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