1) The document describes the preparation and evaluation of sustained release microparticles of the drug norfloxacin using an ionotropic gelation technique. 2) Three formulations were prepared varying the concentration of calcium chloride to investigate its effect on drug entrapment efficiency, swelling, and in vitro drug release. 3) Formulation A2, prepared with 2% w/v calcium chloride, showed the highest drug entrapment efficiency of 54.84% and provided the most sustained drug release over 5 hours of 40.51% compared to the other formulations.

1. PREPARATION AND EVALUATION OF SUSTAINED
RELEASE MICROPARTICLES OF NORFLOXACIN
Prepared & Presented by : -
 RAJA CHAKRAVERTY
M Pharm

2. INTRODUCTION
 Oral controlled drug delivery systems represent the most popular form of sustained drug
delivery systems for the obvious advantages of oral route of drug administration. Such
systems release the drug with constant or variable release rates .
 Attempts to maintain a steady level of medication using biodegradable polymers have
recently attracted considerable attention. Because, these polymers are biodegradable,
they do not require retrieval after the medication is exhausted.
 Therefore, they can be fabricated into microspheres, microcapsules or nanospheres, with
the drug encapsulated in them. Various microencapsulation techniques for incorporating a
bioactive agent into a microparticle carrier are there .
 Some of the advantages of using microparticles as sustained release drug delivery
systems are an effective protection of the active agent against degradation ( e.g. :
enzymatic) after encapsulation(1). The possibility to accurately control the release rate of
the incorporated drug over periods of hours to months an easy administration

3. INTRODUCTION
 The principle of gelation is based on the formation of tight junction between the
glucoronic acid residues of sodium alginate. Number of apparent cross-linking
points formed within the Calcium alginate gel beads increase with increased
alginate concentration.
 The increase in the apparent cross-linking density delays the alginate gel
disintegration in phosphate buffer due to retardation of calcium-ion (Ca++)
exchange with sodium (Na+) and eventually leads to the increase of lag time.
 Ionotropic gelation is based on electrostatic interaction between amine groups
of polymer and negatively charged group of polyanion. Chemical reaction
between sodium alginate and calcium chloride is utilized in micropellet
formation.
 The gelation of alginate is caused by formation of an egg box junction to
associate divalent metal ions of alginate polymer chain. Sodium alginate has
been used as matrix material to achieve a control release drug delivery due to
its hydrogel formation properties. Gelation of an anionic polysaaaccharide,
sodium alginate, was achieved with oppositely charged counter ions i.e. Ca ++
to form microparticles which are further sustained using a divalent polymer.

4. OBJECTIVE
 The objective of this
undertaken project is
the preparation and
evaluation of sustained
release microspheres
of norfloxacin.
NORFLOXACIN

5. PREPARATION OF MICROSPHERES
BY IONOTROPIC GELATION
TECHNIQUE
 PROCEDURE :
 STEPS INVOLVED IN THE GENERAL PREPARATION OF MICROPARTICLES BY IONOTROPIC
GELATION TECHNIQUE :-
 1. First of all, weighed accurately all materials required for the experiment including the drug used
(Norfloxacin), sodium alginate and calcium chloride.
 2. Distilled water is then added to the weighed quantity of sodium alginate to make aqueous mucilage of it
in a beaker and allowed to heat for 5-10 minutes in a hot plate.
 3. Following it, Distilled water is also added to the weighed quantity of calcium chloride to make a solution
in it.
 4. The aqueous mucilage of sodium alginate is then stirred in a magnetic stirrer at a suitable speed (rpm)
for 30 minutes.
 5. The Drug (Here: Norfloxacin) is dispersed in the aqueous mucilage of sodium alginate subsequently
and stirred at suitable speed in the magnetic stirrer.
 6. The microparticles are formed by dropping the bubble free dispersions through a glass syringe with the
help of a needle (size-16/18) into the gently agitated calcium chloride solution in 100ml.
 7. ‘Cured’ the microparticles for 30 mins. and then filtered & washed thoroughly with distilled water.
 8. The pellets were then oven dried for 2-4 hrs at about 50 degree centigrade.
 9. Dried at room temperature subsequently for few hours and used subsequently.

6. STANDARD CURVE OF
NORFLOXACIN
STANDARD CURVE OF NORFLOXACIN IN PHOSPHATE BUFFER PH 6.8 STANDARD CURVE IN 0.1 (N) HCL PH (1.2)
1.2 0.7
0.6
1
y = 0.1677x
y = 0.0971x
0.5
0.8
ABSORBENCE
0.4
ABSORBENCE
Series1 Series1
0.6
Linear (Series1) Linear (Series1)
0.3
0.4
0.2
0.2
0.1
0
0
0 1 2 3 4 5 6 7
0 1 2 3 4 5 6 7
CONCENTRATION (mcg/ml)
CONCENTRATION (mcg/ml)
PHOSPHATE BUFFER
PH 6.8 HCL BUFFER PH 1.2

7. EVALUATION METHODS
 DRUG ENTRAPMENT
EFFICIENCY
 SWELLING INDEX
 IN-VITRO
DISSOLUTION STUDY
FORMULATION DRUG SODIUM CALCIUM
CODE LOADING ALGINATE CHLORIDE
(%W/V)
A1 30 % 200mg 1gm
A2 30 % 200 mg 2 gm
A3 30 % 200 mg 3 gm

8. DRUG ENTRAPMENT EFFICIENCY
 PROCEDURE :
 Accurately weighed microparticles equivalent to 20
mg and suspended in 250 ml of simulated intestinal
fluid pH=6.8 and kept for 24 hours. Next day, stirred
for 5 minutes and filtered. After suitable dissolution,
drug content was analyzed spectrophotometrically at
278 nm. Then Drug Entrapment Efficiency (%) was
determined through formula.

Drug Entrapment Efficiency =
(Actual Drug content / Theoretical Drug
Content) x 100%
 DRUG ENTRAPMENT
EFFICIENCY (A1) = 42. 22 %
 DRUG ENTRAPMENT
EFFICIENCY (A2)= 54.84 %
 DRUG ENTRAPMENT
EFFICIENCY (A3)= 37.52 %

9. SWELLING STUDY
TIME A1 A2 A3
(min ) % swell % swell % swell
0 0 0 0
10 14 16 18
20 24 20 29
30 29 25 39
40 34 31 49
50 39 36 62
60 46 45 69
70 50 49 73
80 55 54 77
% SWELLING VS TIME PLOT 90 61 62 80
100 63 67 81

10. IN-VITRO DISSOLUTION
STUDY
TIME (min) A1 A2 A3
0 0 0 0
TIM
30 13 15.52 17.45
45
40 60 23.8 26.4 23.98
35 90 32.62 33.86 28.6
30
A1
120 33.36 36.14 25.78
25
A2
20 A3
150 36.14 39.79 24.53
15 180 36.17 39.9 24.2
10
210 35.5 39.96 24.13
5
0 240 33.57 40.23 22.07
0 50 100 150 200 250 300 350
270 33.54 40.37 21.99
300 33.4 40.51 21.97
% CUMULATIVE DRUG RELEASE VS TIME
PLOT

11. RESULT & DISCUSSION
 Chemical reaction between sodium alginate and calcium chloride to form
calcium alginate was utilized for microspheres. A1 & A2 exhibited similar
swelling profiles whereas A3 show greater swelling compared to other two
formulations.
 A2 formulation showed best sustained release amongst the three
formulations releasing about 40.51 % in 5 hrs .Formulation A3 showed
greatest percent swelling over time. The Drug Entrapment Efficiency, a
crucial parameter in such formulations is given below :-
 A. Drug entrapment efficiency (A1) = 42. 22 %
 B. Drug entrapment efficiency (A2) = 54.84 %
 C. Drug entrapment efficiency (A3)= 37.52 %

12. CONCLUSION
 Sustained release microparticles were successfully prepared employing
ionotropic gelation technique where the natural water soluble polymer, namely,
sodium alginate prolongs the release of the drug. The method of preparation
was found to be simple and without the use of organic solvents. Micropellets
prepared are spherical in shape and having a porous surface. The Drug
Entrapment Efficiency of formulation A2 prepared with 2%w/v calcium chloride
showed the best result of around 55 % DEE. This could have been further
improved upon by the use of co-polymers.
 The micropellets were found to be effective in sustaining the drug release with
the formulation A2 releasing around 40.51 % drug in 5 hours. Drug release is
diffusion controlled and follows first order kinetics. The process of drug release
from the polymer-dry matrix is through gelation of the polymer. Swelling studies
showed A3 getting swelled up fastest while A2 exhibited least swelling and this
fact is corroborated with the faster dissolution of formulation A3 and the
sustained release effect shown by A2 in the In-vitro Dissolution study.

13. RAJA CHAKRAVERTY M Pharm WBUT