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Formulation and Evaluation of Mucoadhesive Microspheres of Amoxicillin Trihydrate by using Eudragit RS 100

Authors:
  • Sai Nath University

Abstract

Mucoadhesive microspheres include microparticles and microcapsules (having a core of the drug) of 1-1000μm in diameter and consisting either entirely of a mucoadhesive polymer or having an outer coating of it, respectively. Amoxicillin microspheres were formulated by using solvent evaporation technique. Using Eudragit RS 100 as matrix polymer. Evaluation of the prepared mucoadhesive microspheres was done for % yield, particle size analysis, particle size distribution angle of repose, and determination of drug content, shape, surface characterization, drug entrapment and finally cumulative drug release from microspheres by suitable and reliable official methodologies.
International Journal of ChemTech Research
CODEN( USA): IJCRGG ISSN : 0974-4290
Vol.2, No.1, pp 466-470, Jan-Mar 2010
Formulation and Evaluation of Mucoadhesive
Microspheres of Amoxicillin Trihydrate by using
Eudragit RS 100
Faizi Muzaffar1*, N.Venkatesh Murthy1 ,Prasanjit Paul2,
Ravindra Semwal2 ,Pandey Shivanand3
1J K K Nataraja College of Pharmacy, Komarapalayam, Tamil Nadu,India
2Dr K N Modi Institute of Pharmaceutical Education and Research. Modinagar,India
3Smt. R. B. P. M. Pharmacy College, Atkot-360040, Rajkot, Gujarat. India
*Corres.author:faizimuzaffar@gmail.com
Abstract: Mucoadhesive microspheres incl ude microparticles and microcapsules (having a core of the drug) of 1-
1000µm in dia meter and consisting either entirely of a mucoadhesive polymer or having an outer coating of it,
respectively. Amoxicillin micr ospheres were formulated by using solvent evaporation technique. Using Eudragit RS 100
as matrix polymer. Evaluation of the prepared mucoadhesive microspheres was done for % yield, particle size analysis,
particle size distribution angle of repose, and determination of drug content, shape, surface characterization, drug
entrapment and finally cumulative drug release from microspheres by suitable and reliable official methodologies.
Keywords: Mucoadhesive microspheres, Amoxicillin Trihydrate, Eudragit, Angle of repose, characterization
Introduction
It is the most extensively used method of micro
encapsulation first described by Ogawa et
al.1Mucoadhesive microspheres include microparticles
and microcapsules (having a core of the drug) of 1-
1000µm in diameter and consisting either entirely of a
mucoadhesive polymer or having an outer coating of it,
respectively.2Microspheres, in general, have the
potential to be used for targeted and controlled release
drug delivery; but coupling of mucoadhesive
properties to microspheres has additional advantages.
Mucoadhesive and biodegradable polymers undergo
selective uptake by the M cells of payer patches in
gastrointestinal (GI) mucosa3 this uptake mechanism
has been used for the delivery of protein and peptide
drugs, antigens.
Materials and Methods
Amoxicillin Trihydrate and Eudragit RS 100 from
Ranbaxy Pvt. Ltd Guargoan, Edragit RS100 form
Orchid Lab, Chennai, and Span 80 from Loba
Chemicals. Pvt. Ltd. Mumbai, Light Liquid Paraffin,
Acetone AR, Concentrated HCl LR, Potassium
dihydr ogen phosphate AR, Sodium Hydroxide LR
from Nice Chemicals Pvt. Ltd. Cochin, Whatman filter
paper from Research labs fine chemical Mumbai, n-
Hexane from Cheaper, Chennai.
Instruments: Mechanical Stirrer(Elektrocraft Pvt.
Ltd., Mumbai ), UV/VIS spectrophotometer(Elico SL-
164, India), Single pan Digital balance(Shimadzu), Hot
Air Oven(Genuine Lab), Magnetic stirrer(Remi
Stirrer), Optical Microscope(Acculab), Digital pH
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467
meter(Hanna Instrument), FTIR Spectro photometer
(Shimadzu),Scanning Electron Microscope(ZEOL
JSM -5610).
Compatibility studies Fourier Transform Infrared
Spectroscopy (FTIR): One of the requirement for the
selection of suitable excipients or carrier for
pharmaceutical formulation is its compatibility.
Therefore in the present work a study was carried out
using FTIR using SHIMADZU-FTIR 410 model. The
pellets were prepared at high compaction pressure by
using KBr and the ratio of sample to KBr is 1: 1000.
The pellets prepared were exa mined and the spectra of
drug and other ingredients in the formulation were
compared with that of original spectra.
Differential Scanning Calorimetry (DSC): The DSC
analysis was carried out to identify the compatibility
between the drug and excipients. The DSC analysis of
pure drug, 1:1 physical mixture of drug excipient were
carried out using mettler Toledo DSC 821, Switzerland.
Samples (2-8 mg) were accurately weighed and heated
in sealed aluminium pans at a rate of 10o/ min between
0-300 OC temp ranges under nitrogen atmosphere.
Preparation of Mucoadhesive Microspheres by
Solvent Evaporation Technique: Amoxicillin
microspheres were formulated by using solvent
evaporation technique. Using Eudragit RS 100 as
matrix polymer. Eudragit was dissolved in 12 ml of
acetone and the mucoadhesive polymer and drug was
dispersed with the polymer solution (Mucoadhesive
polymer and drug previously passed in sieve no 240).
The dispersed content was placed drop wise in 100 ml
light liquid paraffin containing span80 maintained at
40oC while stirring at 750 ±50 rpm. The solvent,
acetone was then removed by continuous stirring at
room temperature for three hours to produce spherical
microspheres. The micro sphere were than separated
from liquid para ffin by filtration through Whatmann
filt er paper No-44, the microspher es were collected
and washed three times with n-hexane and dried using
vacuum filtration. The product was then air-dried to
obtain microspheres.
Evaluation of the Prepared Mucoadhesive
Microspheres
Determination of % yield of microspheres4:
Thoroughly dried microspheres were collected and
weighed accurately. The percentage yield was than
calculated using formula given
Mass of micro spheres obtained
% yield = x100
Total weight of drug
and polymer
Particle size analysis5
Particle size distribution : Particle size determination
was done by sieving method. Size distribution plays an
important role in determining the release
characteristics of the microspheres. Angle of repose6
Angle of repose was determined by using funnel
method; the accurately weighed spheres were taken in
funnel. The height of funnel was adjusted in such as
way that the tip of funnel just touches the apex of heap
of blends. The blends were allowed to flow through
funnel freely on to surface. The diameter of powder
cone was measured; angle of repose was calculated by
using following equation. Tan q = h/r, Where h
height of pile, q – angle of repose
r – Radius of base.
Determination of drug content: Accurately weighed
100 mg microspheres, were crushed in glass mortar
and pestle and powder microspheres were suspended
in 100 ml of 0.1N HCl. After 12 hours the solution was
filtered and the filtrate was analyzed for the drug
content using UV-Visible spectrophotometer.
Encapsulation efficiency: Encapsulation efficiency
was calculated using the following formula
Encaps ulation efficiency =
Estimated drug content x 100
Theoretical drug content
Swelling studies: A known weight (50 mg) of
microspheres was placed in a glass vial containing 10
ml of distilled water at 37 ± 0.50C in incubator with
occasional shaking. The microspheres were
periodically removed, blotted with filter paper and
their changes in weights were measured during the
swelling until equilibrium was attained. Finally, the
weight of the swollen microspheres was recorded after
a period of 3 hours, and the swelling ratio (SR) was
then calculated from the formula. The studies were
carried out in triplicate.
Swelling Ratio (SR)
We-WO
=
WO
Where, Wo = Initial weight of the dry microspheres,
We = weight of the swollen microspheres at
equilibrium swelling in the media.
In vitro wash-off test7The mucoadhesive property of
microspheres evaluated by an In vitro adhesion testing
method known as wash-off method. Freshly excised
piece of intestinal mucosa (2 x 2 cm) from goat were
mounted on to glass slides (3 x 1 inch) with
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468
cyanoacrylate glue. Two glass slides were connected
with a suitable support, about 100 microspheres were
spread on to each wet rinsed tissue specimen and
immediately thereafter the support was hung on to the
arm of a USP tablets disintegrating test machine.
When the disintegrating test machine was operated, the
tissue specimen was given slow, regular up-and-down
moment in the test fluid (900 ml of 01N HCL) at 37±
0.50C. At the end of 30 min, at the end of one hour,
and at the hourly intervals up to 5 hours, the machine
was stopped and number of microspheres still adhering
to tissue was calculated. The studies were carried out
in triplicate.
In vitro dissolution studies6Dissolution studies were
carried out for all the formulation, employing USP
XXIII apparatus (Basket method) at 37± 0.5
0
C
rotated at constant speed of 50 rpm using 0.1N HCL as
the dissolution medium. A sample of microspheres
equivalent to 100 mg of amoxicillin trihydrate was
used in each test. An aliquot of the sample was
periodically with drawn at suitable time interval and
the volumes were replaced with fresh dissolution
medium in order to maintain the sink condition. The
sample was analyzed spectrophotometrically at 272
nm.
Kinetics of drug release8In order to understand the
mechanism and kinetic of drug release, the drug
release data of the in-vitro dissolution study were
analyzed with various kinetic model like zero order,
first order, Higuchi’s Papa’s and Coefficient of
correlation (r) values were calculated for the liner
curves by regress ion analysis of the above plots.
Shape and surface characterization The shape and
surface characterization of microsp heres were
observed under a Scanning Electron Microscope
(SEM). The instrument used for this study was ZEOL
JSM – 5610 scanning electron microscope. The
microspheres were mount ed directly on the SEM
sample stub, using double-sided sticking tape, and
coated with gold film (thickness 200 nm) under
reduced pressure (0.001 torr) and photographed.
Results and Discussions
Pre formulation studies for drug and carrier
interaction .
Angle of repose: The angle of repose is in between 22
to 25orevealed that the microspheres of all the batches
had good flow characteristics and flow rates. Fourier
Transform Infrared Spectroscopy (FTIR): The
identification of drug was done by IR spectroscopy.
The IR spectrum of pure drug Amoxicillin trihydrate is
shown below which was concordant with the reference
spectrum of Amoxicillin trihydrate.150 when the wave
number of Amoxicillin trihydrate was compared with
the standard peaks, the peaks were similar and by this
the purity of drug can be confirmed. The FTIR spectral
analys is showed that there was no appearance or
disappearance of any characteristic peaks of pure drug
amoxicillin trihydrate in the physical mixture of drug
and polymer, which confirms the absence of chemical
interaction between drug and polymers. The DSC
spectral analysis also reveals the same.
Differential Scanning Calorimetry (DSC): The DSC
analysis was carried out to identify the compatibility
between the drug and excipients. The DSC analysis of
pure drug, 1:1 physical mixture of drug excipient were
carried out using mettler Toledo DSC 821, Switzerland.
Samples (2-8 mg) were accurately weighed and heated
in sealed aluminium pans at a rate of 10o/ min between
0-300 OC temp ranges under nitrogen atmosphere.
The thermogram of pure drug showed endothermic
peak at - 124.180 OC.The physical mixture of drug
and excepient shows peak at 126.517 OC.
Particle size distribution: The microsphere prepared
by this method was found to be discreet, spherical, free
flowing and it was observed by scanning electron
microscopy (SEM)
In vitro dissolution studies: The percentage yield of
microspheres of all formulation was in the range of
78.90% to 90.95%.
Shape and surface characterization The XRD
analys is of final formulation shows that the peak
intensity of Amoxicillin Trihydrate slightly reduced it
indicates that the crystallinity of Amoxicillin
Trihydrate slowly reduced in formulation.
Conclusion
In the present work effort have been made to design
and evaluate Mucoadhesive microspheres of
Amoxicillin trihydrate and the results obtained in the
study have been summarized below. A 23 full factorial
design was perfor med to study the effect of
formulation variables (concentration of polymers) on
the release properties by applying optimization
technique. The polymer concentration is a major factor
affecting the release and mucoadhesion strength of the
prepared microspher es. The observed r esponse (t90%)
is close agreement with the predicted t90% valu e ther e
by demonstrating the feasibility of the optimization
procedure in developing mucoadhesive microspheres
containing Amoxicillin trihydrate.
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Drug Content of Mucoadhesive Microspheres of Amoxicillin Trihydrate
Formulation Code *Percentage drug content (% ± SD)
F1 80.22 ± 0.99
F2 75.04 ± 1.08
F3 79.03 ± 1.09
F4 78.56 ± 0.47
F5 80.10 ± 1.00
F6 82.15 ± 0.61
F7 72.03 ± 1.55
F8 81.46 ± 1.11
Data for Percent Entrapment Efficiency of Formulation of Mucoadhesive
Microspheres of Amoxicillin Trihydrate
Formulation
Code
Theoretical drug
content in%
Practical drug
content in%
Entrapment Efficiency in
%
F1 28.73 23.05 80.22
F2 54.74 41.08 75.04
F3 20.32 16.06 79.03
F4 43.35 34.06 78.56
F5 18.24 14.61 80.10
F6 40.10 32.94 82.15
F7 14.45 10.40 72.03
F8 40.06 32.63 81.46
Graphs: 1 Graphs: 2
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470
Graphs: 3 Individual Microsphere
Surface View of Microsphere Groups of Microspheres
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Comparative Dissolution Study
0
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120
0 2 4 6 8
T im e (hr s)
% CDR
%CD R F1
%CD R F2
%CD R F3
%CD R F4
%CD R F5
%CD R F6
%CD R F7
%CD R F8
... The microspheres were periodically removed, blotted with filter paper and their changes in weights were measured during the swelling until equilibration was attained. Finally, the weight of the swollen microspheres was recorded after a period of 3 hours, and the swelling ratio (SR) was then calculated from the formula (Shivanand et al., 2010). ...
... The medium was replaced with 5 ml of fresh buffer each time. The absorbance was measured by UV spectrophotometer at the wavelength of 291 nm and % cumulative release of the formulations was calculated (Shivanand et al., 2010). ...
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... When the disintegrating apparatus was operated, the tissue specimen was subjected a slow, regular up and down movement in the test fluid (phosphate buffer, pH 7.4) at 37°C. At specific time intervals like 0.5, 1, 2, 3, 4, 5 and 6 h, the apparatus was stopped and number of microcapsules adhering to mucosal tissue was counted 18,19 . Percentage mucoadhesion was determined by following formula: ...
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Mucoadhesive drug delivery system
  • M A T H I O W I T Z E , C H I C K E R I N G D E , J A C O B J S
M a t h i o w i t z E, C h i c k e r i n g D E, J a c o b J S, Mucoadhesive drug delivery system, U.S. Patent, 2001; 6:,346.
Intestinal transit of bioadhesive microspheres in an i n s i t
  • C M Lehr
  • J A Bowstra
  • J J Tukker
  • H E Junginer
Lehr CM, Bowstra JA, Tukker JJ, Junginer HE, Intestinal transit of bioadhesive microspheres in an i n s i t u l o o p i n t h e r a t, Journal of Controlled Release, 1990; 13: 51-62.