The document discusses the formulation and evaluation of glibenclamide microsphere drug delivery system. The objective was to increase the drug's self-life by developing a microsphere delivery system. Two batches of glibenclamide microspheres were prepared using different polymers and manufacturing methods. Batch 2, prepared via spray congealing with agar polymer, showed more sustained release over 12 hours compared to Batch 1 and was considered the optimized formulation. In vitro drug release studies found Batch 2 followed zero-order kinetics. The microspheres were characterized and evaluated for properties like particle size, drug entrapment efficiency, and in vitro drug release kinetics. The study achieved sustained drug release to improve bioavailability and patient compliance.

1. FORMULATION AND
EVALUATION OF
GLIBENCLAMIDE
MICROSPHERE DRUG
DELIVERY SYSTEM
By
PAYEL MUKHERJEE
ROLL NO: 2080191405
REG NO: 142080210054 OF 2014-2015
Under the Guidance of
Mr. MAYUKH JANA
Asst. Professor Dept. Of Pharmaceutics

2. OBJECTIVE
The objective of the project work to increase the self-life
of the drug by microsphere drug delivery system. T1/2
of Glibenclamide in table is 10 hours .We can increase
the t1/2 as well as self-life of the drug and also reduce
the dose by this formulation

3. CONTENTS
INTRODUCTION
DEFINITION
ADVANTAGE
DISADVANTAGE
IDEAL CHARACTERISTICS OF MICROSPHERES
CLASSIFICATION OF MICROSPHERES
FORMULATION
MANUFACTURING PROCESSES
EVALUATION OF MICROSPHERES
APPLICATIONS
EXPERIMENTAL METHODS
RESULT AND DISCUSSION
CONCLUSION
REFERENCES

4. INTRODUCTION
Microspheres are characteristically free flowing powders consisting of
proteins or synthetic polymers which are biodegradable in nature and
ideally having a particle size less than 200 µm. A well designed
controlled drug delivery system can overcome some of the problems of
conventional therapy and enhance the therapeutic efficacy of a given
drug. To obtain maximum therapeutic efficacy, it becomes necessary to
deliver the agent to the target tissue in the optimal amount in the right
period of time there by causing little toxicity and minimal side
effects^1 . There are various approaches in delivering a therapeutic
substance to the target site in a sustained controlled release fashion.
Among them micro spheric drug delivery system has gained enormous
attention due to its wide range of application as it covers targeting the
drug to particular site to imaging and helping the diagnostic features

5. DEFINITION
 The term MICROSPHERE is defined as a spherical particle
with size varying from 50nm to 2µm, containing a core
substance. Microspheres are, in strict sense, spherical empty
particles. However, the terms microspheres and
microencapsulation are used synonymously. In addition, some
related terms are “beads” are used alternatively. Spheres and
spherical particles are also used for a large size and rigid
morphology. The microspheres are characteristically free
flowing powders consisting of proteins or synthetic polymers,
which are biodegradable in nature, and ideally having a particle
size less than 200 micrometer.

6. ADVANTAGES
 Particle size reduction for enhancing solubility of the poorly
soluble drug.
 Provide constant drug concentration in blood there by
increasing patent compliance
 Decrease dose and toxicity.
 Reduce the dosing frequency and thereby improve the patient
compliance
 Better drug utilization will improve the bioavailability and
reduce the incidence or intensity of adverse effects.
 Convert liquid to solid form & to mask the bitter taste.
 Controlled release delivery biodegradable microspheres are
used to control drug release rates thereby decreasing toxic side
effects, and eliminating the inconvenience of repeated injections

7. DISADVANTAGES
 Reproducibility is less.
 The costs of the materials and processing of the controlled
release preparation, are substantially higher than those of
standard formulations
 Process conditions like change in temperature, pH, solvent
addition, and evaporation/agitation may influence the
stability of core particles to be encapsulated
 The environmental impact of the degradation products of
the polymer matrix produced in response to heat,
hydrolysis, oxidation, solar radiation or biological agents

8. IDEAL CHARACTERISTICS
OF MICROSPHERES
 The ability to incorporate reasonably high
concentrations of the drug.
 Stability of the preparation after synthesis with a
clinically acceptable shelf life.
 Controlled particle size and dispersability in aqueous
vehicles for injection.
 Release of active reagent with a good control over a
wide time scale.
 Biocompatibility with a controllable biodegradability.
 Susceptibility to chemical modification.

9. TYPES OF MICROSPHERES
 Bioadhesive microspheres
 Magnetic microspheres
 Floating microspheres
 Radioactive microspheres
 Polymeric microspheres :
 Biodegradable polymeric microspheres
 Synthetic polymeric microspheres

10. FORMULATION

11. MANUFACTURING
PROCESSES
 Spray Drying
 Solvent evaporation
 Single emulsion technique
 Double emulsion technique
 Phase separation coacervation technique
 Spray congealing
 Solvent extraction
 Quassi emulsion solvent diffusion
 Polymerization techniques

12. POLYMERIZATION

13. SPRAY CONGEALING
DROPLETS OF DRUG POLYMER SOLUTION IS ADDED SLOWLY
TO THE LIQUID PARAFFIN
MICROSPHERES ARE PREPARED BY SEPATING AND WASHING
WITH n-HEXANE
COOLED LIGHT LIQUID PARAFFIN IS PLACED UNDER
CONTINUOUS STIRRING
HOT DRUG POLYMER SOLUTION IS TAKEN INTO THE SYRINGE
LIQUID PARAFFIN IS COOLED
AGAR POLYMER IS HEATED WITH DRUG

14. EVALUATION
 Particle size and shape:
The most widely used procedures to visualize microparticles are
conventional light microscopy (LM) and scanning electron microscopy
(SEM).
 Electron spectroscopy for chemical analysis:
The surface chemistry of the microspheres can be determined using the
electron spectroscopy for chemical analysis (ESCA).
 Density determination:
The density of the microspheres can be measured by using a multi volume
pycnometer.
 Isoelectric point:
The micro electrophoresis is used to measure the electrophoretic mobility of
microspheres from which the isoelectric point can be determined.

15. EVALUATION
 Angle of contact:
The angle of contact is measured to determine the wetting
property of a micro particulate carrier.
 In vitro methods:
Release studies for different type of microspheres are carried out
by using different suitable dissolution media, mostly by rotating
paddle apparatus (USP / BP).
 Drug entrapment efficiency:
Drug entrapment efficiency can be calculated using following
equation, % Entrapment = Actual content/Theoretical content *100.
 Swellingindex:
The swelling index of the microsphere was calculated by using the
formula, Swelling index= (mass of swollen microspheres - mass of dry
microspheres/mass of dried microspheres)*100.

16. APPLICATION
o Ophthalmic Drug Delivery
o Oral drug delivery
o Gene delivery
o Nasal drug delivery
o Intratumoral and local drug delivery
o Buccal drug delivery
o Gastrointestinal drug delivery
o Transdermal drug delivery
o Colonic drug delivery
o Vaginal drug delivery

17. EXPERIMENTAL METHOD
 TRIAL 1:
 TRIAL 2:
INGREDIENTS QUANTITY
1.Glibenclamide (DRUG)
2.Agar
3.Liquid Paraffin Light
4.Water
0.25gm
0.5gm
25ml
25ml
INGREDIENTS QUANTITY
1.Glibenclamide (DRUG) 0.1gm
2.Ethyl cellulose 0.25gm
3.Sodium alginate 1gm
4.Calcium chloride 5gm
5.Water 75ml

18. PREPARATION OF STANDARD
CURVE
Preparation of standard stock solution:
Standard drug solution of Glibenclamide was prepared by dissolving 10mg
in 10ml chloroform (1mg/ml) and transfer 1ml of this solution to 10ml of
volumetric flask, made upto mark with same solvent. For obtaining clear
solution, solution was filtrated.
Preparation of calibration curve:
Aliquots of 0.5 to 3ml of portion of stock solution were transferred to a
series of 10ml volumetric flask and made upto mark with solvent
(chloroform). Solutions were scanned in the range of 200-400 nm against
blank. The absorption maximum was found to be at 242 nm against blank.
The caliberation curve was plotted.

19. CALIBRATION CURVE
CONCENTRATION ABSORBANCE
0 0
5 0.066
10 0.207
15 0.302
20 0.432
25 0.535
30 0.598
y = 0.0211x - 0.0111
R² = 0.9925
-1
0
1
0 5 10 15 20 25 30 35
ABSORBANCE
CONCENTRATION (mcg/ ml)
STANDARD CURVE OF GLIBENCLAMIDE
Series1 Linear (Series1)

20. Time (mins) % Cumulative Drug
Release B1
% Cumulative Drug
Release B2
10 0.091 0.012
20 1.119 0.097
30 2.228 1.062
40 5.986 1.981
50 8.762 2.549
60 11.298 3.002
70 15.391 4.992
80 17.221 5.815
90 20.011 7.832
100 28.336 11.381
110 34.345 16.231
120 40.231 20.68
In vitro dissolution study of Batch No. B1& B2.

21. y = 34.809x - 44.57
R² = 0.7446
-20
-10
0
10
20
30
40
50
0 0.5 1 1.5 2 2.5
CUM%DRUGRELEASED
LOG T
FIRST ORDER RELEASE KINETICS OF B1
Cumulative % DR B1 Linear (Cumulative % DR B1)

22. y = 0.1249x - 2.5433
R² = 0.9704
-4
-2
0
2
4
6
8
10
12
14
16
0 20 40 60 80 100 120 140
Cumulative%DrugRelease
Time (mins)
ZERO-ORDER RELEASE KINETICS OF BATCH B2
Cumulative %of Drug released

23. EVALUATION OFMICROSPHERES
 The prepared batches of microspheres were characterized for
their micromeritic properties (Particle size, angle of repose, bulk
density, tapped density and Carrs index) and encapsulation
efficiency as per the standard procedures reported in
literatures.The in vitro dissolution of batch EC5 was carried out
in 900 ml of pH 1.2 Buffer as the dissolution medium using USP
Type II apparatus apparatus at 75 rpm. The temperature was
maintained at 37 ± 0.5°C. The dissolution was carried out for 24
hours. The sampling volume was 5 ml. The time points included
were 10 mins to 2 hrs. The absorbance’s of the sample at
different time intervals were carried out using UV visible
spectrophotometer (UV 1800, Shimadzu) at λmax of 242 nm.
The drug release was calculated using calibration curve subjected
to various kinetic models such as zero order and first order to
study the mechanism of release of drug from microspheres.

24. RESULT AND DISCUSSION
 Glibenclamide drug loaded microspheres were prepared
by two different methods , they were discrete, spherical,
and free flowing. The results indicated that all the
prepared microspheres possess good flow property.
 The in vitro release data indicated that both batches
show satisfactory sustained release through
microspheres for 2 hrs but Batch no. B2 showed
maximum sustained release than batch no B1 and hence
was considered as optimized batch. .
 The Batch 2 is the Spray congealing method and Batch 1
is he Cross linking method.
 B2 showed the better activity as the process contains
Agar as polymer.

25. CONCLUSION
Microspheres of glibenclamaide using different polymers
and different preparation method were successfully
prepared and evaluated. The types of polymer and
preparation method influence the drug release as the
polymer level was increased , the drug release rates were
found to be decreased B2. It was observed that Ethyl
Cellulose possessing less retaining capacity than the Agar.
In vitro drug release studies revealed that the formulation
in B2 was found to be finest formulation. The mechanism
of drug release for formulation B2 was found to be zero
order process. The aim of this study was achieved by
sustaining the drug release for 12 h thereby it improves the
bioavailability of drug followed by patient compliance and
gives better treatment. Hence, it is recommended that there
is a lot of scope for future in vivo studies.

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28. THANK YOU..