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FORMULATION AND EVALUATION OF CAPECITABINE IN COLON TARGETING
1. ENHANCEMENT 0F SOLUBILITY OF SELECTED MODEL DRUGBY LIQUID-SOLID
COMPACTIONTECHNIQUE
FORMULATION AND EVALUATION OF CAPECITABINE
LOADED SODIUM ALGINATE MICROBEADS FOR
COLON TARGETING
THESIS SUBMITTED TO BIJU PATNAIK UNIVERSITY OF TECHNOLOGY FOR
THE AWARD OF THE DEGREE OF
MASTER OF PHARMACY
IN
PHARMACEUTICS
SUBMITTED BY
RAKESH CHANDRA PARIDA, B.Pharm.
Regd. No- 1508267030
UNDER THE ESTEEMED GUIDANCE OF
Mr. GOUTAM KUMAR JENA
M. Pharm. , Asst. Professor
DEPARTMENT OF PHARMACEUTICS
ROLAND INSTITUTE OF PHARMACEUTICAL SCIENCES, BERHAMPUR, ODISHA (2017) 1
4. 4
1.INTRODUCTION
DEFINITION- Colon drug delivery system refers to targeted
delivery of drug in to the lower parts of GI tract , mainly large
intestine.
The major goal of any drug delivery system is to supply a
therapeutic amount of drug to a target site in a body.
A targeted drug delivery system is preferred in drugs having
instability, low solubility and short half life
Targeted delivery of drugs to the colon is usually to achieve one
or more of four objectives.
To reduce dosing frequency .
To delay delivery to the colon to achieve high local concentrations
in the treatment of diseases of the distal gut.
To delay delivery to a time appropriate to treat acute phases of
disease.(chrono therapy).
To deliver to a region that is less hostile metabolically, e.g., to
facilitate absorption of acid and enzymatically labile materials,
especially peptides.
5. 5
ANATOMY OF COLON :-
The GIT consists of parts from mouth to anus. It mainly consists of two
parts namely stomach, intestine. The intestine includes small intestine
and large intestine.The GIT measures about 5 meters long. The different
parts of GIT are divided into upper and lower gastrointestinal tract. The
upper GIT includes oesophagus, stomach, and duodenum. The lower GIT
includes small intestine and large intestine. The small intestine measures
an average of about 6.9 meters to 7.1 meters. It include duodenum,
jejunum and ileum. The main function of small intestine is the absorption
of nutrients and minerals from food. The retention time of small intestine
is 3-5 hr. The large intestine measures about 1.5metres long. It includes
caecum, colon and rectum. The main function of large intestine is to
remove the water and minerals from the food and it sends the
indigestible matter to the rectum.The retention time of large intestine is
3-10hr.
6. 6
The colon consists of four parts: ascending colon, transverse colon,
descending colon and sigmoid colon. It extracts water and salts from solid
wastes before they are eliminated from the body. The parts of colon are
located either in the abdominal cavity or behind it in retro peritoneum. The
ascending and descending colon and rectum are retroperitoneal, while
transverse colon is intra peritoneal. The pH of colon varies from 5.5 to 7.
Transit time of different parts of GIT pH in different parts of Colon
Part Of GIT Transist
Time
Fasted state 10min – 2hr
Fed state >2hr
Small intestine
transit
3-4hr
Colon transit 20-35hr
Part of GIT pH
Stomach
Fasted state
1.5-2
Fed state 2-6
Small Intestine 6.0- 6.8
Colon
Ascending colon
Transverse colon
Descending colon
7.0
7.2
7.4
7. 7
MICROPARTICLES :-
These are the particles with size more than ‘1’m, containing the polymer.
At present, there is no universally accepted size range that particles must
have in order to be classified as microparticles. However, many workers
classify the particles smaller than ‘1’m, as nonparticles and those more than
1000 m as macroparticles.
CLASSIFICATION :
Micro particles are classified into two groups:
MICROCAPSULES
Microcapsules have an either spherical geometry with a continuous core
region surrounded by a continuous shell or have an irregular geometry and
contain a number of small droplets
MICROSPHERES:-
Microspheres are solid, spherical particles containing dispersed drug
molecules, either in solution or crystalline form, among the polymer
molecules.
Microparticles
Microcapsules
(Micrometric
Reservoir Systems)
Microspheres
(Micrometric Matrix
Systems)
8. 8
TYPES OF MICROSPHERES:
1. Bioadhesive microspheres
These kinds of microspheres exhibit a prolonged residence time at the site
of application and causes intimate contact with the absorption site and
produces better therapeutic action.
2. Magnetic microspheres
These kind of delivery system is very much important which localises the
drug to the disease site.
3. Diagnostic microspheres
It can be used for imaging liver metastases and also can be used to
distinguish bowel loops from other abdominal structures by forming nano
size particles supramagnetic iron oxides .
4. Polymeric microspheres
The different types of polymeric microspheres can be classified as follows
and they are biodegradable polymeric microspheres and Synthetic polymeric
microspheres. Biodegradable polymeric microspheres Natural polymers such
as starch are used with the concept that they are biodegradable,
biocompatible, and also bio adhesive in nature
9. 9
5.Radioactive microspheres
Radio emobilisation therapy microspheres sized 10-30 nm. They are
injected to the arteries that lead to tumour of interest. So all these
conditions radcioactive microspheres deliver high radiation dose to the
targeted areas without damaging the normal surrounding tissues.
6. Floating microspheres
Floating types the bulk density is less than the gastric fluid and so remains
buoyant in stomach without affecting gastric emptying rate. The drug is
released slowly at the desired rate.
Various methods of preparations of Microspheres
Emulsion solvent evaporation technique
Emulsion cross linking method
Co-acervation method
Spray drying technique
Emulsion-solvent diffusion technique
Multiple emulsion method
Ionic gelation
Solvent extraction
11. 11
SL .NO DRUG WORK RESULT
1 CAPECITABINE Formulation and Evaluation of
Coated Microspheres for Colon
Targeting.
Coated microspheres of 5-
FlChitosan is used as
polymeruorouracil (FU).
Eudragit S100 coating of
chitosan microspheres was
performed by oil-in-oil solvent
evaporation method using
coat: core ratio (5:1).
2 SATRANIDAZOLE Design and Dev. of Satranidazole
Microsphere For Colon Targeted
Drug Delivery
The release rate was much
slower; however, the drug was
released quickly at pH 7.4. It is
concluded from the present
investigation that Eudragit
microspheres are promising
controlled release carriers for
colontargeted delivery of
satranidazole.
3 CAPECITABINE Formulation And Charecterisation
Of Colon Targeted pH Dependent
Microspheres Of Capecitabine For
Col.orectal Cancer
PH-sensitive polymer Eudragit
L100, S100 separately and in
combination (1:2) was used to
formulate the microspheres by
emulsion solvent diffusion
technique using varying drug –
polymer ratios (1:2 to 1:6).
2. LITERATURE REVIEW
12. 12
04
MELOXICAM
Formulation And Evaluation Of
Meloxicam Loaded Microspheres For
Colon Targeted Drug Delivery
The present investigation that
Eudragit-coated sodium
alginate microspheres are
promising controlled
release carriers for colon-
targeted delivery of Meloxicam
05 TINIDAZOLE
Formulation and development of
Tinidazole Microspheres for colon
targeted drug delivery System
The release rate was
Much slower; however, the drug
was released quickly at
pH7.4.It is concluded from the
present investigation that
Eudragit microspheres are
promising as a carrier for
colontar-geted delivery of
Tinidazole.
06 TELMISARTAN
Formulation and evaluation of
controlled-release of Telmisartan
microspheres: In vitro/in vivo study
The release mechanism was
studied by comparing the values
of correlation coefficients, and
the drug release was found to
be controlled by diffusion of
drug through the microsphere
matrix (TMRS formulation). The
Higuchi model was found to be
the best fitted for drug release
from telmisartan microspheres
of TMRS formulations.
14. 3. AIM AND OBJECTIVE
In recent years, microspheres have been proven to deliver drugs
efficiently to the target site with improved bioavailability.
The objective of present research work is to prepare microspheres
using Capecitabine.
In order to achieve the aim, the following objectives have been set:
To reduce the side effect.
To controlled the drug release .
To enhance the bioavailability in colonic site.
14
15. PLAN OF WORK
Preformulation Studies:-
Characterization of Active Pharmaceutical Ingredient by determining
organoleptic parameters and analytical evaluation.
Solubility studies of pure drug and polymer.
Formulation Studies:-
To select suitable cross linking agents such as CaCl2 & ZnSO4, Polymer such
as Sodium Alginate , Eudragit S100 & Eudragit L100.
Preparation of Sod. Alginate microspheres by Ionic Gelation method.
Determination of drug release profile of microparticles.
Determination of swelling property of formulation in different solvents.
Observation of average particle size of microspheres.
Determination of dissolution rate of microspheres prepared for
Capecitabine.
Encapsulation of microspheres using different coating materials.
Determination of drug entrapment efficiency of various microsphere
formulations.
Determination of Mucoadhesive property of formulation.
15
17. 17
4.DRUG PROFILE
CHEMICAL STRUCTURE :-
CAPECITABINE
MOLECULAR WEIGHT :- 359.350083 G/MOL
MOLECULAR FORMULA :- C15H22FN3O6
GENERIC NAME :- Capecitabine
TRADE MAN :- Xeloda
CHEMICAL NAME:- Pentyl N[1[(2R,3R,4S,5R)3,4dihydrox
5methyloxolan2yl]5fluoro2oxopyrimidin4yl] carbamate.
DESCRIPTION :- Off white or almost white crystalline powder
M.O.A:- Nucleic acid synthesis inhibitor.
THERAPEUTIC CATEGORY:- Anti cancer drug
18. 18
DOSE:- 150-500mg.
BIOLOGICAL HALF LIFE:- 45-60 minutes
M.P:- 110-1210c
BIOAVAILABILITY:- 80-90% (extensive)
SOLUBILITY :- Insoluble in water, 0.1N HCl,Glacial acetic acid and soluble
in acetone, ethanol, 0.1N NaOH, phosphate buffer pH 6.8 and solubility is
highest in phosphate buffer pH 7.6.
STORAGE:- Capecitabine should be stored in tightly closed containers at 25
0C but may be exposed to temperatures of 15-30 0C.
USES:- CapecItabine is a deoxycytidine derivative and fluorouracil Prodrug
that is used as an Antineoplastic Antimetabolite in the treatment of Colon
Cancer, Breast Cancer and Gastric Cancer.
ADVERSE EFFECTS:- Most common advese reactions are headache,
abdominal pain, constipation , Nausea , Vomiting and Diarrhoea.
20. 20
SL.NO Name of the material MANUFACTURER
1 Capecitabine Gift sample from college
2 Sodium Alginate Gift sample from college
3 Eudragit L 100 Evonik , India
4 Eudragit S 100 Evonik , India
5 CaCl2
Merck, India
6 ZnSO4
Merck, India
7 Acetone Triveni Chemicals
8 Glacial acetic acid Arihant chemicals
MATERIALS USED
21. 21
EQUIPMENT USED
SL.
NO
EQUIMENTS MODEL/MANUFACTURER
1 Digital balance BS223S, Sartorius, India
2 UV-Visible Spectrophotometer UV-1800, Shimadzu, Japan
3 Mechanical shaker REMI, India
4 Ultra sonicator Enartech, India
5 Magnetic stirrer Tarsons, Multispin, India
6 Optical microscope Magnus, MLX, India
7 6-Stage USP-I Dissolution
Apparatus
Electrolab, India
8 Disintegration Apparatus Electrolab, India
23. 23
Active Pharmaceutical Ingredient (API) characterization:-
Evaluation of API:
1. Organoleptic properties:
2. Analytical properties:
UV Spectroscopic Analysis:
1. Determination of ƛmax of Capecitabine by UV Spectroscopy
method:
A Stock solution of Capecitabine (1000 µg/ml) was prepared by taking 10 mg
of drug to a small volume of solution in a 10ml volumetric flask and shaked
for few seconds and made upto the volume. From this, 1ml was pipetted out
and made upto 10ml using phosphate buffer pH 7.4 solution to obtain a
concentration of 100 µg/ml. From this, 1ml was taken and diluted to 10ml
using the same buffer solution and was scanned on UV- Visible
Spectrophotometer using a scan speed of 238nm/min, data interval 0.1nm
and slit width 1.0nm in the range of 200-400nm. The wavelength of
maximum absorbance (ƛmax) was determined.
EXPERIMENTAL WORK
24. 24
Conc. In
µg/ml
Absorbance
0 0
3 0.102
6 0.216
9 0.347
12 0.461
15 0.569
18 0.699
21 0.831
1.PREPARATION OF CALIBRATION CURVE FOR CAPECITABINE.
A. Preparation Of Phosphate Buffer Ph7.4 (1000ml).
B. Preparation of Sample Solution:
0
0.102
0.216
0.347
0.461
0.569
0.699
0.831
y = 0.039x - 0.012
R² = 0.999
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 10 20 30
A
b
s
o
r
b
a
n
c
e
Concentration (µg/ml)
Series1
Linear (Series1)
25. 25
SOLUBILITY STUDIES:
Excess quantity of the pure drug was added to freshly prepared
simulated gastric fluid(0.1N HCl), water, simulated intestinal
fluid(phosphate buffer pH 6.8 and 7.4), and other organic solvents like
acetone, ethanol etc into clean vials. It was shaken in a mechanical
shaker at 25+0.5oc for 24hrs.Then it was filtered and 1ml of filtrate was
collected in 10ml volumetric flasks and diluted up to the mark
respectively. Then the absorbances of the samples were collected by
using U.V spectrophotometer at 238 nm. The polymer was found to be
completely soluble in glacial acetic acid.
Table : Solubility of Drug in Various solvents
SOLVENT ABSORBANCE CONCENTRATION
(µg/ml)
CONCENTRATION
(mg/ml)
Water 1.134 344.54 0.344
0.1NHCl 0.381 101.61 0.101
PH 6.8 1.527 471.29 0.471
PH 7.4 1.567 483.23 0.483
26. 26
FORMULATION AND OPTIMIZATION OF MICROSPHERES :
Preparation Of Sodium Alginate Microspheres By Ionotropic
Gelation Method:
First of all weighed accurately all materials required for the experiment
including the drug used Capecitabine , Sodium alginate , calcium chloride and
zinc sulphate.
The weighed different formulation quantity of Capecitabine drug was dissolved
in 5% of Glacial acetic acid aqueous solution.
Distilled water was added to the weighed different formulation quanty of
sodium alginate to make aqueous mucilage of in a beaker.
The aqueous mucilage of sodium alginate was stirred in a magnetic stirrer at a
suitable speed (rpm) for 30minutes.
The drug Capecitabine was dispersed in the glacial aqu. Solution and aqueous
mucilage of sodium alginate mix susiquently stirred at suitable speed in the
magnetic stirrer.
Distilled water was also added separate beaker to the 10% W/W quantity of
calcium chloride and Zinc Sulphate .
The microparticle were formed by dropping the bubble free dispersions
through a glass syringe with the help of needle size 18 into the gently agitated
in different solution like calcium chloride , zinc sulphate and calcium chloride &
zinc sulphate solution in 100ml.
The microsphere for 30 mins and was filtered and wash thoroughly distilled
water .
The microsphere was dried in hot air oven for 2-4 hrs at 500c and evaluated.
28. 28
Table : Formulation Of Capecitabine Loaded Sodium alginate Microsphere
For 10 % of calcium chloride aqueous solution.
Formulation code Drug (mg) Polymer (mg) Drug :
Polymer
Ratio
Cacl2 Aqu.
Solu.
(% w/v)Sodium Alginate
R1 100 400 1:4 10
R2 100 600 1:6 10
R3 100 800 1:8 10
R4 100 1000 1:10 10
R5 100 1200 1:12 10
R6 100 1400 1:14 10
These are three different formulation I was found in best formulation result
of Capecitabine Loaded Sodium alginate Microsphere For 10 % of calcium
chloride and Cacl2 & Znso4 aqueous solution.
29. 29
OPTIMIZATION PROCESS OF VARIABILITY :-
In order to explore the influence of formulation and preparative variables of
the Ionic gelation technique on the formation of microsphere and their size
, polymer ,selection of solvents and their ratio were studied in order to
control and optimized the process.
Optimization Parameters Process variables
Drug polymer ratio (constant: RPM,) 1:4
1:6
1:8
1:10
1:12
1:14
Rotational speed in RPM (constant: Drug-
polymer ratio)
300
500
700
ENCAPSULATION OF CAPECITABINE LOADED SODIUM ALGINATE MICROSPHERES:-
•Microsphers were coated with Eudragit S 100 and Eudragit L 100 ata concentration of 1:1
ratio respectively.
•Microspheres were dispersed in Eudragit S 100 and Eudragit L 100 solution prepared in
10% w/v of acetone at room temperature.
•Stirring was continued for 3hours at room temperature in order to evaporate the solvent
completely.
•Encapsulated microspheres were filtered and dried.
31. 31
RESULTS & DISCUSSION
DRUG ENTRAPMENT EFFICIENCY :
The amount of Drug Entrapment was calculated by the formula
% Drug Entrapment Efficiency= Experimental Drug Content / Theoritical
Drug Content x 100
Table : Drug Entrapment Efficiency of Formulation Of Capecitabine Loaded
Sodium alginate Microsphere For 10% of Calcium chloride and Cacl2 &
Znso4 aqueous solution.
Formulation
(Drug+polymer)
Entrapment
Efficiency (%)
Formulation
(Drug+polymer)
Entrapment
Efficiency (%)
F1 72.47 R1 67.43
F2 75.64 R2 69.21
F3 77.14 R3 72.45
F4 79.04 R4 73.12
F5 81.26 R5 75.18
F6 82.78 R6 76.63
The drug entrapment efficiency of all the formulations were determined
and it was found that the % drug entrapped were increased with
increase in drug and polymer ratio.
32. 32
The Swelling index was calculated by the formula
Swelling Ratio = Final weight – Initial weight / Initial weight x 100.
Table : Swelling Index for Formulation of (Cacl2 & Znso4 aqueous
solution).
SWELLING INDEX :
SOLVENT
% SWELLING INDEX
F1 F2 F3 F4 F5 F6
1. PH 6.8 5 7 6 9 8 10
2. 0.1N HCL 6 8 10 15 18 21
3. Water 5 8 10 13 11 15
0
5
10
15
20
25
F1 F2 F3 F4 F5 F6
%SWELLING
FORMULATION
% Swelling PH. 6.8
% Swelling 0.1N HCL
% Swelling Water
34. 34
AVERAGE PARTICLE SIZE DETERMINATION:
10 divisions of eye piece = 15 divisions of stage micrometer.
1 division of eye piece = 15/10 or 1.5 divisions of stage micrometer.
As, 100 divisions = 1mm
1 division = 0.01mm
So, Correction factor = 1.5*0.01 =0.015nm or 15µm.
Table : Average particle size of microsphere.
Range(µm) Mean
Range(µm)(d)
Total number of
microspheres(n)
n*d
30-40 35 52 1820
40-50 45 18 810
50-60 55 11 605
70-90 80 10 800
100-110 105 9 945
∑n=100 ∑n*d=4980
The average particle size was determined by using the Edmondson’equation =
Dmean= nd/n
Where , n – Total number of microsphere observed.
d- Mean size range.
Average particle size of microsphere in µm=∑n*d/∑n
=4980/100=49.8µm.
35. 35
MUCOADHESIVE PROPERTY
The mucoadhesive property of microspheres was evaluated by an in vitro adhesion
testing method . Freshly excised piece of goat stomach mucous were mounted on to
glass slides. About 20 microspheres were spread on to each prepared glass slide and
immediately there after the slides were hung to USP II tablet disintegration test
apparatus. When the test apparatus was operated the sample is subjected to slow up
and down movement Buffer ph 7.4 at 370 C . At 8 hour the machine was stopped and
number of microspheres still adhering to mucosal surface was counted.
% Mucoadhesion = Number of microspheres adhered/Number of microspheres applied
x 100.
Table : Mucoadhesion Property for Formulation of (Cacl2 & Znso4 aqueous
solution).
Formulat
ion
No of
Microsphere
Applied
No
Microspher
e Adhered
%
Mucoadhesion
F1 20 16 80
F2 20 18 90
F3 20 18 90
F4 20 19 95
F5 20 17 85
F6 20 18 90
70
75
80
85
90
95
100
R1 R2 R3 R4 R5 R6
%MUCOADHESION
FORMULATION
%
Mucoadhes
ion
% Muco adhesion of different formulation.
36. 36
Table : Mucoadhesion Property for Formulation of (Cacl2 aqueous solution)
Formulation No of Microsphere
Applied
No Microsphere
Adhered
% Mucoadhesion
R1 20 15 75
R2 20 17 85
R3 20 18 90
R4 20 19 95
R5 20 17 85
R6 20 18 90
70
75
80
85
90
95
100
R1 R2 R3 R4 R5 R6
%
MUCOADHESION
FORMULATION
% Mucoadhesion
The drug Mucoadhesion Property of all the formulations were
determined and it was found that the % Mucoadhesion was best in F4
and R4 formulation in 95% Mucoadhesion.The Mucoadhesion were
increased with increase in drug and polymer ratio.
37. 37
IN-VITRO DRUG RELEASE STUDIES:
PROCEDURE:
The dissolution technique was used of Capecitabine from microsphere
system. The receptor media used was 0.1N HCL for 2hrs then same
formulation put into 6.8 phosphate buffer for 10hrs then same formulation
put into the pH 7.4 phosphate buffer for 12hrs medium (900ml) was studied
by using a dissolution test apparatus with a Basket type stirrer. The entire
system was kept at 370C. 50mg equivalent of the drug formulation was
added and rotated at 100 rpm. Samples (5ml) from dissolution medium were
withdrawn and filtered at different interval of time and were assayed for
capecitabine Loaded sodium alginate content at 238 nm against blank.
39. 39
0
20
40
60
80
100
120
0 5 10 15 20 25 30
%CUMULATIVEDRUGRELEASE
TIME IN HOURS
Zero Order Plot
% CU DR F1
% CU DR F2
% CU DR F3
% CU DR F4
% CU DR F5
% CU DR F6
Fig. of Zero Order Plot of Drug Release Kinetics
From the above Results, It has been Found that the Cumulative %
Drug Release is best shown by Formulation With Drug & Polymer ratio
1:10 & 1:14 in Formulation F4 and F6. It has also been found that
there is an increase in release with increase in concentration of
polymer .
40. 40
Table : R2 Values Of different Plots :
Formulations
(Cacl2 & Znso4 )
Zero order R2 First order R2 Higuchi plot
R2
Korsmeyer-
peppa’ s R2
F1 0.987 0.654 0.889 0.973
F2 0.990 0.737 0.890 0.974
F3 0.992 0.775 0.897 0.975
F4 0.994 0.792 0.917 0.983
F5 0.991 0.798 0.914 0.973
F6 0.993 0.801 0.916 0.982
Analysis of drug release data from various plots such as Zero order , First
order, Higuchi and Korsmeyer Peppa’s Plot and the R2 Value presented in the
Table . We were found in R2 Value obtained from zero order kinetics.
42. 42
0
20
40
60
80
100
120
0 5 10 15 20 25 30
%CUMULATIVEDRUGRELEASE
TIME IN HOUR
Zero Order Plot
% CU DR R1
% CU DR R2
% CU DR R3
% CU DR R4
% CU DR R5
% CU DR R6
Fig. Of Zero Order Plot of Drug Release Kinetics
From the above Results, It has been Found that the Cumulative % Drug Release is
best shown by Formulation With Drug & Polymer ratio 1:10 in Formulation R4. It has
also been found that there is an increase in release with increase in concentration of
polymer .
43. 43
Table : R2 Values Of different Plots :
Formulations
(Cacl2 aqu.
solu )
Zero order
R2
First order
R2
Higuchi plot
R2
Korsmeyer-
peppa’ s R2
R1 0.992 0.760 0.913 0.968
R2 0.989 0.777 0.893 0.970
R3 0.990 0.779 0.894 0.976
R4 0.993 0.794 0.911 0.988
R5 0.989 0.751 0.889 0.969
R6 0.990 0.778 0.897 0.974
Analysis of drug release data from various plots such as Zero order , First
order, Higuchi and Korsmeyer Peppa’s Plot and the R2 Value presented in
the Table . We were found in R2 Value obtained from zero order
kinetics.
44.
45. 45
SUMMARY & CONCLUSION
SUMMARY :-
From this experimental work, Microspheres prepared by using only
CaCl2 as Cross linking agent showed spherical shape but does not control
the better release upto 24 hr as that of combined effect as ZnSo4 & CaCl2
solution.
The Microspheres prepared by ZnSo4 alone also does not produced
Spherical spread microspheres & also not able to control the drug release
upto 24 hrs. when both ZnSo4 & CaCl2 solution were used combinedly as
cross linking agent produced microspheres which were spreaded in shape
, maximize yield & control l the drug release upto 24 hrs.
Hence cross linking effect can be enhanced when both ZnSo4 & CaCl2
were used combinedly solution.
The drug release study data from various plot such as zero order , first
order , Higuchi plot & Korsmeyer peppa’s plot. We were found in R2 value
obtained from Zero order Kinetics.
CONCLUSION :-
Microspheres can be prepared by Ionotropic gelation technique by using
both ZnSo4 & CaCl2 Solution as cross linking agent which can better
conroll drug release upto 24 hr, maximized yield, produce spherical
shape.
46.
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50. ACKNOWLEDGEMENT:
Special thanks to
Prof. (Dr.) M.E. Bhanaji Rao,
M.Pharm, Ph.D.,Principal,
Roland Institute of Pharmaceutical
Sciences
Berhampur.
Prof. (Dr.) Ch. Niranjan Patra
M. Pharm., Ph.D., Professor
Deparment of Pharmaceutics
All my dearest colleagues, seniors, teaching and non teaching staff
members of Roland Institute of Pharmaceutical Sciences.
Mr. Goutam Kumar Jena
M. Pharm., Asst. Professor
Deparment of Pharmaceutics
