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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

Available Online at www.ijprbs.com 89

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.

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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



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.



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.



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



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



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


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




λmax.

C. Determination of absorption maxima of in 1N NaOH


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.

D. Determination of absorption maxima of esomeprazole in 0.1 N HCl


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.

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



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.



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.



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



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



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



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



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


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


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


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



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



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



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



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)



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



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



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



(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



(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



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



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



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



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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