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Asian J. Pharm. Res. Vol 3, Issue 2, 75-79, 2013.
e-ISSN 2231 – 363X
Print ISSN 2231 – 3621
FORMULATION AND EVALUATION OF MICROSPHERES OF
CFFDINIR
1K.Ramadevi, 1S.Janet Beula, *1Raju Bathula, 2G.E Suhasini, 3M.Nirmala
1Department of Pharmaceutical Chemistry, Avanthi Institute of Pharmaceutical Sciences, JNTU, Hyderabad,
Andhra Pradesh, India.
2Department of Pharmaceutical Chemistry, St.Marry’s College of Pharmacy,
JNTU, Hyderabad, Andhra Pradesh, India.
3Department of Chemistry, Osmania University, Hyderabad, Andhra Pradesh, India.
ABSTRACT
Microspheres are sub-micron size polymeric drug carrier systems in which the therapeutic agents are loaded
micrometer. These particles consist of core material, which is the drug, and a coating material. Microspheres are considered as a
very promising controlled and targeted drug delivery system. The formulation and clinical application of microspheres is based
on the physicochemical pharmacokinetic and pharmacological properties of drugs. Cefdinir is a beta-lactam antibiotic and is
mainly bactericidal. Cefdinir inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to
specific penicillin binding proteins; those are located inside the bacterial cell wall. Cefdinir is the third generation anti-biotic
used for the treatment of community -acquired pneumonia, acute bacterial otitis media and uncompleted skin and skin structure
infections in adult and pediatric patient. Incorporation of Cefdinir in polymeric microspheres can successfully increase the
biological half-life and reduce the therapeutic dose of their drug, thereby minimizing the adverse drug reaction. Cefdinir
microspheres were formulated by emulsion solvent evaporation method using ethyl cellulose polymer. All the above studies
reveal that the microsphere can serve as an ideal drug delivery system for Cefdinir. Further studies can be done on the stability
of cefdinir-loaded microspheres and the improvement in therapeutic efficacy due to the targeting effect on to the specific
receptor sites.
Key words: Microspheres, Cefdinir, Antibiotic, Ethyl Cellulose and chloroform.
INTRODUCTION
Microspheres are submicron size polymeric drug
carrier systems in which the therapeutic agents are loaded
inside the polymeric matrix or encapsulated or physically
absorbed or chemically coupled on to the surface. The size
range of these colloidal particles is from 1-1000 micro
meter .These particles consist of core material ,which is the
drug and a coating material [1].The coat material can be of
various types ranging from natural polymers such as
albumin, gelatin [2], chitosan [3] and synthetic such as
poly(vinyl alcohol) [4], poly(lactate-co-glycolide) [5] and
combination of two polymers such chitosan sodium CMC
[6] and alginate –chitosan [7] etc. The microspheres are
characteristically free flowing powders consist of proteins
or synthetic polymers that are biodegradable in nature [8],
and ideally having a particle size less than 200 micro meter
.Solid biodegradable microspheres incorporating a drug
dispersed or dissolved throughout particle matrix have the
potential for the controlled release of drug [9]. These
carriers received much attention not only for prolonged
release but also for the targeting of the anti-cancer to the
tumor. Microspheres are effective for delivery of both the
entrapped and absorbed antigen [10]. Microspheres are
applied for diseased cell sorting, diagnostics genes and
genetic materials [11,12].
MATERIALS AND METHODS
Drug-Cefdinir
Polymer-CMC & Methyl Cellulose [13,14]
Solvent-Chloroform
Corresponding Author :- Raju Bathula Email:- rajucool050320@gmail.com
Asian Journal
of
PHARMACEUTICAL RESEARCH
Journal homepage: - www.ajprjournal.com
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Asian J. Pharm. Res. Vol 3, Issue 2, 75-79, 2013.
Methods
Preparation of Reagents
Phosphate Buffer P H 7.4
Dissolve 2.38gm of disodium hydrogen phosphate,
0.19 gm of Potassium dihydrogen phosphate and 8gm of
NACL in sufficient water to produce 1000 ml. Adjust the
P H if necessary
Preparation of Standard Curve
Accurately 50 mg of drug was dissolved in 50 ml of
phosphate buffer. A stock solution was prepared by
withdrawing 10 ml of the above solution and made up to
100 ml. From the stock solution 2 ml, 4 ml, 6 ml, up to 20
ml were taken and made up to the volume in a 100 ml
volumetric flask to get a concentration of 2 µgm, 4 µgm,
6µgm up to 20µgm respectively. Then the absorption was
measured at 220nm using phosphate buffer pH 7.4 as
blank. The absorbance of the drug at various
concentrations is enlisted in table 1 and the standard plot is
shown in Fig: 1.
Preparation of Microspheres
Microspheres are prepared by emulsion solvent
evaporation method employing chloroform as a solvent for
the polymer [11]. Ethyl cellulose polymer is dissolved in
chloroform to form a homogenous solution. Core material
is added to the polymer solution and mixed thoroughly.
The resulting mixture is then added in a thin stream to 200
ml of an aqueous mucilage of sodium carbaoxy methyl
cellulose (0.5%)contained in a beaker with constant
stirring at 1000rpm to emulsify the added dispersion as
fine droplets. The solvent chloroform was then removed
by continuous stirring at room temperature for 3 hrs to
produce spherical microspheres. The microspheres are
collected by vacuum filtration and washed repeatedly with
water. The produc t is then air - dried to obtain discrete
microspheres [12-14].
RESULTS AND DISCUSSION
Cefdinir is the third generation anti-biotic used for
the treatment of community –acquired pneumonia, acute
bacterial exacerbations of chronic bronchitis, acute
maxillary sinusitis, pharyngitis, tonsillitis, acute bacterial
otitis media and uncompleted skin and skin structure
infections in adults and pediatric patient. Incorporation of
Cefdinir in polymeric microspheres can successfully
increase the biological half –life and reduce the dose of
their drug, their by minimizing the adverse drug reaction.
Cefdinir in ethyl cellulose microspheres were prepared
and its physico chemical parameters were evaluated.
Morphological Structure
The external appearance of the cefdinir
microspheres were smooth and pure white in colour
.Cefdinir were spherical, discrete in shape and covered
with coating material.
Particle Size Analysis
The size distributions of the various batches of
microspheres were determined by optical microscope. The
average particle size of the various batches of Cefdinir
micro spheres are shown in table 3. The mean size of the
microspheres was increased as the proportion of coat
material in the microspheres was increased.
Drug Loading Analysis
The drug content was increased with the ratio of
polymer. The drug content was maximum with CEFMS-3,
which indicates that the increased in the particle size also
favours the drug loading capacity. The drug contents are
given in table 3.
Table 1. Standard Curve of Cefdinir
Concentration micro gram/ml
Absorbance
2
4
6
8
10
12
14
16
18
20
0.064
0.135
0.205
0.276
0.346
0.418
0.475
0.525
0.583
0.632
Table 2. Formula for the Preparation of Microspheres
S No
Batch Code
Concentration Of Drug
Concentration
Of Polymer
Drug
Polymer ratio
Concentration of NaCMC
1
MS
-
100mg
-
0.5%
2
CEFMS1
50 mg
50 mg
1:1
0.5%
3
CEFMS2
50 mg
100mg
1:2
0.5%
4
CEFMS3
50 mg
150mg
1:3
0.5%
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Asian J. Pharm. Res. Vol 3, Issue 2, 75-79, 2013.
Table 3. Characterization of Cefdinir Microspheres
S No
Batch Code
Drug Polymer Ratio
Particle Size (μm±s.d)
Drug Content(%)
1
CEF
-
90±3.58
-
2
CEFMS1
1:1
175±3.39
45.2
3
CEFMS2
1:2
180±4.25
53.1
4
CEFMS3
1:3
395±6.2
62.8
Table 4. Invitro Release Profile of Cefdinir Microspheres
Time in hrs
Free drug (%)
CEFMS-1 (%)
CEFMS-2 (%)
CEFMS-3 (%)
1
39.6
13.2
9.5
6.3
2
64.5
21.8
23.4
12.5
3
97.5
26.2
35.4
20.2
4
-
31.9
41.4
25.6
5
-
38.5
53.4
33.2
6
-
46.2
56.4
42.2
7
-
53.2
61.4
54.5
8
-
60.4
66.8
58.5
9
-
69.4
71.5
65.4
10
-
75.5
76.5
70.3
11
-
81.5
83.2
74.5
12
-
86.4
85.4
76.8
13
-
90.7
89.2
78.2
14
-
96.5
91.4
82.6
15
-
99.3
94.5
85.4
16
-
99.3
98.2
89.4
17
-
99.3
98.2
92.7
18
-
99.3
98.2
94.3
19
-
99.3
98.2
96.5
20
-
99.3
98.2
97.3
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Asian J. Pharm. Res. Vol 3, Issue 2, 75-79, 2013.
Invitro Release Studies
The invitro release of the Cefdinir from
microspheres are enlisted in table 4 and graphically
represented in figure 2.All the three batches of Cefdinir
exhibited sustained release for about period of 12 hrs
(CEFMS-1)to 20 hrs. All the three batches exhibited a
biphasic release pattern in which about 60%(approval ) of
the drug was released within 5 hrs (CEFMS-1) to 10 hrs
(CEFMS-3). This burst release will be quiet effective in
achieving the minimum effective concentration
(MEC)whereas the remaining 40% was released slowly
and this may help to maintain the plasma drug
concentration with in the therapeutic range .This biphasic
release of the drug from the microspheres may be due to
the quick release of the drug molecule adsorbed on the
surface of the microspheres. The constant release of the
remaining drug from inner polymeric matrix may be by
the mechanism leaching.
CONCLUSION
Microspheres are one of the most promising
controlled and targeted drug delivery systems. Cefdinir is
a broad spectrum antibiotic having low plasma half-life.
Hence, it was formulated in microspheres to improve the
therapeutic efficacy thereby reducing the development of
drug resistance. Cefdinir Microspheres were formulated
by emulsion solvent evaporation method using ethyl
cellulose polymer. All the above studies reveal that the
microsphere can serve as an ideal drug delivery system for
cefdinir. Further studies can be done on the stability on
cefdinir loaded microspheres and the improvement in
therapeutic efficacy due to the targeting effort on to the
specific receptor sites.
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