DEVELOPMENT & CHARACTERIZATION OF

ORAL MICROPARTICULATE DRUG

DELIVERY SYSTEM

Presented By Guided By
Akshada P. Visal Dr. Savita J. Tauro

1 Department Co-guided By
Pharmaceutical Quality Assurance Dr. Govind S. Asane

ST. JOHN INSTITUTE OF PHARMACY & RESEARCH

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 1.INTRODUCTION
2

 The termed multi-particulate drug delivery system is defined as the pharmaceutical

formulations in which the active substance present as number of small independent
subunits.
 It is mainly applies to multiple particles such as pellets, beads, microspheres,
microcapsules.
 Multi-particulate drug delivery systems (MDDS), mostly used for oral route, consist
of multiplicity of small discrete units that exhibit different characteristics. Together,
these characteristic units provide the overall desired controlled release of the dose.
 In MDDS, drug substances are divided into number of subunits, typically consist of
thousands of spherical particles having diameter of about 0.05-2.00 mm. To administer or
to recommend total dose these subunits are compressed into a tablets or filled into a sachets
or encapsulated

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 Fig no. 1- multi-particulate drug delivery system

 The particle size of less than 2 mm facilitates uniform drug absorption of the drug over the
large surface area in GIT and more uniform drug absorption profile is assured compared to
conventional unit dosage forms.
3  This kind of particular distribution of dosage form assures more consistency in
bioavailability by avoiding the problem of dose dumping

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 ADVANTAGES
4

 Increase bioavailability

 Alter the drug release & separation of reactive core from other materials.

 Improve the patient’s compliance

 Predictable, reproducible and short gastric residence time.

 Reduced adverse effects and improved tolerability.

 Limited risk of local irritation.

 No risk of dose dumping.

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 TYPES OF MULTIPARTICULATE SYSTEM
5

MICROPARTICLES

MICROSPHERES

MICROCAPSULES

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6 MICROPARTICLES MICROSPHERES MICROCAPSULES

Microparticles are defined as Microspheres are small Microencapsulation is a

particulate dispersions or spherical particles, with process by which solids,
solid particles with a size in diameters in the micrometer liquids or even gases may be
the range of 1 μm -1000μm. range typically 1 μm to 1000 enclosed in microscopic
μm particles by formation of thin
coatings of wall material
around the substances.
EXAMPLES- EXAMPLES- EXAMPLES-
Lansoprazole Risperidone Aspirin
Prednisolone Naltrexone Allopurinol
Ranitidine Leuprolide Zidovudine
Ketoprofen Octreotide Nifedipine
Cimetidine Lanreotide Theophylline

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 MICROSPHERES
7
 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
1000 µm.
 Due to its small particle size, are widely distributed throughout the gastrointestinal tract
which improves drug absorption and reduces side effects.
 microencapsulation technology allows protection of drug from the environment,
stabilization of sensitive drug substances, elimination of incompatibilities, or masking of
unpleasant taste.
 This approach allows the accurate delivery of small quantity of the potent drugs, reduced
drug concentration at the site other than the target site and the protection of the labile
compound before and after the administration and prior to the site of action
 Microspheres can be used for the delivery of drugs via different routes. Route of
administration is selected depending on the drug properties, disease state being treated and
the age and condition of the patient. Desirable properties of the microspheres to be used for
the delivery will also change depending on the route of administration.

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 TYPES OF MICROSPHERES
8
 Bio adhesive microspheres

 Magnetic microspheres

A) Therapeutic microspheres

B) Diagnostic microspheres

 Floating microspheres

 Radioactive microspheres

 Polymeric microspheres

A) Biodegradable polymeric microspheres

B) Synthetic polymeric microspheres

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 METHODS TO FORMULATE
9

 Ionic gelation method

 Emulsion solvent evaporation technique

 Emulsion cross linking method

 Coacervation phase separation

 Spray drying technique

 Emulsion –solvent diffusion technique

 Multiple emulsion method

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  IONIC GELATION METHOD-
10

 Ionotropic gelation is based on the capability of polyelectrolytes to crosslink in the

presence of counter ions.

 The ionic gelation method is most frequently used for the preparation of alginate
nanoparticles.

 The three dimensional structure and presence of other groups influence the ability of
cations (or anions) to conjugate with anionic (or cationic) functionalities and some kind of
selectivity is found.

 In this technique the accurately weighed quantity of drug is added into the dispersion of
polymer. Then this homogeneous dispersion is dropped using syringe needle 16G into
slowly agitated solution of calcium chloride.

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11
Mechanism of Drug Release from Microspheres

 Diffusion:
On contact with aqueous fluids in the gastrointestinal tract (GIT), water diffuses into the
interior of the particle. Drug dissolution occurs and the drug solutions diffuse across the
release coat to the exterior.

 Erosion:
Some coatings can be designed to erode gradually with time, thereby releasing the drug
contained within the particle. The polymer erosion, i.e. loss of polymer is accompanied by
accumulation of the monomer in the release medium. The erosion of the polymer begins
with the changes in the microstructure of the carrier as the water penetrates within it
leading to the plasticization of the matrix.

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 2.AIM & OBJECTIVES
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 AIM-
The present study is aimed to develop and evaluate microspheres of
Metronidazole for better treatment of Amoebiasis and other protozoal infections.
metronidazole could prevent unwanted systemic side effects and subsequently a
lower dose of the drug may be sufficient to treat protozoal infections.

 OBJECTIVES-
The development of efficient oral drug delivery system includes advantages like:
 Maximized absorption rate is mainly due to intimate contact of drug with the mucus
membrane to improve and enhance bioavailability of drugs.
 Drug protection is improved by polymer encapsulation and longer gut transit time is
obtained, resulting in extended periods for absorption.
 Multiple dosing is avoided and there by counteracts the side effects.
 The main objective is mainly to develop microspheres of Metronidazole by ionic
gelation process using bioadhesive polymers release of the drug for extended period of
time.
 To study the effect of different polymers and different ratios of polymers employed.
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 3.PLAN OF WORK
13
PLAN OF WORK
Literature survey
Selection of drug, polymers
Procurement of drugs & polymers
Calibration curve
Characterization of drug (IR & DSC)
Preformulation
Formulation (factorial design)
Evaluation of formulation
Stability studies
In-vivo studies
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TIMELINE
Ongoing
From 6/7/2019 to 19/7/2019
From 20/7/2019 to 19/8/2018
From 21/8/2019 to 27/8/2019
From 28/8/2019 to 17/9/2019
Till the mid of October
Mid of November
Mid of December
Till the end of December
Mid of January
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 4.EXPERIMENTAL WORK
14

 A) Procurement of drugs- Racecadotril Macleod pharma limited

Metronidazole Macleod pharma limited

HPMC K4M Colorcon Asia pvt Ltd.

 Procurement of excipients-
HPMC K15M Colorcon Asia pvt Ltd.
HPMC K100M Colorcon Asia pvt Ltd.

 Procurement of chemicals- Hydrochloric acid Loba chemie pvt ltd

Calcium chloride Loba chemie pvt ltd
Barium sulphate Loba chemie pvt ltd
Di-sodium hydrogen phosphate Loba chemie pvt ltd
Potassium dihydrogen phosphate Loba chemie pvt ltd

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 B) CALIBRATION CURVE
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 Calibration curve of metronidazole-
Calibration curve of metronidazole in 0.1 N HCl
stock solution of metronidazole was prepared. From this stock solution final working standard
solutions for calibration curve was prepared in the concentration range of 5-25 ppm were
prepared.

y = 0.0366x + 0.0057 ABSORBANCE

AB S O RB ANCE (Λ =276NM) R² = 0.9998 (λmax=276nm)
1 0.917 Linear
0.9 (ABSORBANCE
0.8 0.74 (λmax=276nm))

0.7
ABSORBANCE

0.55
0.6
0.5
0.375
0.4
0.3 0.194
0.2
0.1 0
0
0 5 10 15 20 25 30
CONCENTRATION (PPM)

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 CALIBRATION CURVE
16
 Calibration curve of metronidazole-
Calibration curve of metronidazole in phosphate buffer pH 6.8
stock solution of metronidazole was prepared. From this stock solution final working standard
solutions for calibration curve was prepared in the concentration range of 5-30 ppm were
prepared.

y = 0.0366x + 0.0125
AB S O RB ANCE AT Λ MAX 320NM R² = 0.9992 ABSORBANCE at
λmax 320nm
1.2 1.108

0.935 Linear
1 (ABSORBANCE at
0.73 λmax 320nm)
ABSORBANCE

0.8
0.555
0.6
0.39
0.4
0.208
0.2
0
0
0 5 10 15 20 25 30 35
CONCENTRATION(PPM)

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 C) CHARACTERIZATION OF DRUG WITH
17
POLYMER
 The characterization of the following samples will be performed using FT-IR & DSC

1) MTZ

2) MHP4

3) MH15

4) MH100

5) MH415100

6) MTSA

7) MTC34

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 D) FUTURE WORK
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 Preformulation

 Formulation

 Evaluation- 1) particle size & shape determination

2) drug entrapment efficiency

3) swelling index

4) in-vitro drug release/dissolution

5) in-vivo studies (X-ray)

 Characterization

 Stability studies

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19 1) PREFORMULATION- it includes identification and characterization of drugs calibration
curve, drug excipient interaction studies.
2) FORMULATION- metronidazole microspheres will be prepared by ionic gelation method.
And also by using 32 factorial design.
3) EVALUATION-
 Particle size determination- particle size of microspheres will be determined by using digital
screw gauge.
 Drug entrapment efficiency- the drug in microspheres will be determined by using indirect
method.
 Swelling index- the swelling behaviour of the microspheres will be evaluated in 0.1 N HCl and
in phosphate buffer 6.8
 In-vitro drug release- the dissolution studies will be performed using Electrolab dissolution rate
test apparatus.
 In-vivo studies- X-ray studies

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20
4) CHARACTERIZATION-

characterization of formulation will be performed by using FT-IR & DSC.

5) STABILITY STUDIES-

To evaluate the long-term stability (2 years), the selected formulations is stored at 40°C ± 2°C/

75% ± 5% relative humidity (RH) for 6 months in a humidity chamber and observed for

physical change and drug content. At the end of storage period, the formulations is also

subjected to drug release studies in intestinal fluids.

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 REFERENCES
21
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  Siraj Shaikh, G. J. Khan, Shaikh Salman, Fakir Heena and Shaikh Shaoor, Shaikh Mohsin F.
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  Sapana P Ahirrao, Parag S Gide, B Shrivastav, and Pankaj Sharma. “Ionotropic Gelation: A
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THANK YOU
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