Microparticle Drug delivery system

1. BY: Deepak Chandra Sharma
GUIDED BY: Mr. Pranshu Tangri
(PROFESSOR OF PHARMACEUTICS)

2.  Microspheres can be defined as solid, approximately spherical particles ranging in
size from 1 to 1000 μm.
 Made up of polymeric, waxy, or other protective materials such as starches, gums, proteins,
fats, and waxes and used as drug carrier matrices for drug delivery.
 Microcapsules: micrometric reservoir systems
 Microspheres: micrometric matrix systems.
 Natural polymer can also be used:
 Albumin
 Gelatin
2

3. 3
Drug Core
Polymer Coat
= Polymer Matrix
} = Entrapped Drug
MICROCAPSULES MICROSPHERES
•Microspheres are essentially spherical
in shape, whereas, microcapsules may be spherical or non-spherical
in shape.
•Microparticles, either microcapsules
or microspheres, as the same: ‘microcapsules’.

4.  Alternative Terms used in place of microspheres:
 Microbeads
 Beads
4

5.  They facilitate accurate delivery of small quantities of potent drug and reduced
concentration of drug at site other than the target organ or tissue.
 They provide protection for unstable drug before and after administration, prior to
their availability at the site of action.
 They provide the ability to manipulate the in vivo action of the drug, pharmacokinetic
profile, tissue distribution and cellular interaction of the drug.
 They enable controlled release of drug.
• Ex: narcotic, antagonist, steroid hormones 5

6.  Microcapsule: consisting of an encapsulated core particle. Entrapped substance
completely surrounded by a distinct capsule wall.
 Micro-matrix: Consisting of homogenous dispersion of active ingredient in particle.
6
Microcapsule Micromatrix
Types of Microspheres

7. Biodegradable
• Lactides &
Glycolides and
their copolymers
• Polyanhydrides
• Polycynoacrylates
Non-biodegradable
• Poly methyl
methacrylate
• Acrolein
• Epoxy Polymer
• Glycidyl
methacrylate
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9. Longer duration of action
Control of content release
Increase of therapeutic efficacy
Protection of drug
Reduction of toxicity
Biocompatibility
Sterilizability
Relative stability
Water solubility or dispersibility
Bioresorbability
Targetability
Polyvalent
9

10. • Taste and odour masking
• Conversion of oil and other liquids, facilitating ease
of handling
• Protection of the drug from the environment
• Delay of volatilisation
10

11. • Freedom from incompatibilities between drug and
excipients, especially the buffers
• Improvement of flow properties
• Dispersion of water insoluble substance in aqueous media
• Production of sustained release, controlled release and
targeted medication
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 Solvent evaporation method
 Single emulsion technique
 Double emulsion technique
 Coacervation phase separation method
 Spray drying and spray congealing method
 Polymerization method

13. A. Single Emulsion Technique
Aq solution
/suspension of
polymer(natural
polymer)
stirring /
sonication
Dispersion in Organic
phase oil/CHCl3
cross
linking
Heat denaturation (by
adding dispersion
To heated oil)
Chemical crosslinking
(butanol,HCHO,Glutara
ldehyde) 14

14. Microspheres in
org.phase
Microspheres in
org.phase
Centrifugation, washing, &
separation
Microspheres
14

15. B. Double Emulsion Technique
Aqueous solution of polymer
dispersion in oil/orgenic phase, vigorous homogenisation(sonication)
Primary emulsion(w/o)
addition of aqueous solution of PVA
W/O/W multiple emulsion
Addition of large aqu. phase
Microspheres in solution
16

16. Separation, washing, drying
MICROSPHERES
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17. 17
C)Polymerization
A)Normal Polymerization
 Normal Polymerization is done by bulk, suspension, precipitation, emulsion and polymerization process.
1. Bulk polymerization:
Microsphere
s
Moulded/fra
gmented
Polymer
(block)
Heated to
initiate
polymerizatio
n
Initiator
accelerate
rate of
reaction
Monomer
+
Bioactive
material
+
Initiator

18. 18
B)Suspension polymerization
Monomer Bioactive material Initiator
Dispersion in water and stebilizer
Droplet
Vigorous Aggitation Polymerization by Heat
Hardened microspheres
Separation & Drying
MICROSP HERES

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c)Emulsion Polymerization
Monomer/ Aq.Solution of NaOH,
Bioactive material Initiator, Surfactant , Stabilizer
Dispersion with vigorous stirring
Micellar sol. Of Polymer in aqueous medium
Polymarization
Microspheres formation
MICROSPHERES

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D)Phase Separation Coacervation
Aq./organic solution of polymer
Drug dispersed or dissolved in the polymer solution
Phase sepration by salt addition, non solvent
addition
add. Incompatible polymer,etc
Polymer rich globules
Hardening
Microspheres in aqu./organic phase
separation/drying
MICROSPHERES

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E)Spray Drying
Polymer dissolve in volatile organic solvent(acetone,dichloromethane)
Drug dispersed in polymer solution under
high speed homogenization
Atomized in a stream of hot air
Due to solvent evaporation small droplet or fine mist form
Leads to formation of Microspheres
Microspheres separated from hot air by cyclone separator, Trace of
solvent are removed by vacuum drying

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F)Solvent Extraction
Drug is dispersed in organic solvent
(water miscible organic solvent such as Isopropanol)
Polymer in organic solvent
Organic phase is removed by extraction with water
(This process decreasing hardening time for microspheres)
Hardened microspheres

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G)Precipitation Method
 An emulsion is formed, which consists of polar droplets dispersed in a non-polar
medium. Solvent may be removed from the droplets by the used of a co-solvent.
 The resulting increase in the polymer-drug concentration causes a precipitation
forming a suspension of microspheres.

24. Oral delivery
Parenteral delivery
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25. 1. Degradation controlled monolithic system.
2. Diffusion controlled monolithic system.
3. Diffusion controlled reservoir system.
4. Erodible poly agent system.
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26. Electron Microscopy, Scanning Electron Microscopy and Scanning
Tunneling Microscopy – Surface Characterization of Microspheres
Fourier Transform Raman Spectroscopy or X-ray Photoelectron
Spectroscopy –to Determine If Any Contaminants Are Present
Surface Charge Analysis Using Micro-electropshoresis –Interaction
of Microspheres Within the Body
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The most widely used procedures to visualize micro particles are conventional light
microscopy (LM) and scanning electron microscopy (SEM).

29. LM provides a control over coating parameters in case of double walled microspheres. The
microspheres structures can be visualized before and after coating and the change can be
measured microscopically.
SEM allows investigations of the microspheres surfaces and after particles are cross-sectioned,
it can also be used for the investigation of double walled systems.
Conflocal fluorescence microscopy is used for the structure characterization of multiple walled
microspheres.
Laser light scattering and multi size coulter counter other than instrumental methods, which can
be used for the characterization of size, shape and morphology of the microspheres.
29

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31.  It is done by using rotating paddle apparatus and
 Dialysis method
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 Determine wetting properties of Microparticulate carriers

32. The surface chemistry of the microspheres can be determined using the electron
spectroscopy for chemical analysis (ESCA). ESCA provides a means for the
determination of the atomic composition of the surface. The spectra obtained
using ECSA can be used to determine the surfacial degradation of the
biodegradable microspheres.
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33.  Used to determine the degradation of the polymeric matrix of the carrier
system.
 Surface of microspheres are investigated by ATR.
 ATR-FT-IR provides surface composition of microspheres.
33
IR spectra
of surface
material
Reflected
many times
through the
sample
IR beam is
passed
through the
ATR cell

34.  Can be determined by using MULTI VOLUME PYCHNOMETER
34
Weigh
sample in
a cup
Placed in
Multi
volume
pychnomet
er
Helium is
introduced
in the
chamber
and
allowed to
expand
Expansion
results in
decrease
in pressure
2 readings
are noted
of
reduction
in pressure
at different
initial
pressure
From 2
reading
volume as
well as
density is
determined

35.  The micro electrophoresis is an apparatus used to measure the electrophoretic
mobility of microspheres from which the isoelectric point can be determined.
 Mean velocity at different Ph values ranging from 3-10 is calculated by
measuring the time of particle movement over a distance of 1 mm.
 using this data the electrical mobility of the particle can be determined.
 The electrophoretic mobility can be related to surface contained charge,
ionisable behaviour or ion absorption nature of the microspheres.
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36.  Measured by using RADIOACTIVE GLYCINE
36
C14 glycine ethyl
ester hydrochloride
Microspheres
Radioactive
glycine
conjugate
EDAC

37.  RADIOACTIVITY is then measured by using LIQUID SCINTILLATION
COUNTER
 Carboxylic acid residue can be find out
37

38. Beaker Method
• Dosages form is adhere to the bottom of the beaker
containing medium.
• Overhead stirrer is used.
• Volume of medium-50-500ml
• Speed 60-300rpm
38

39. A. Oral
cavity
containing
drug in buffer
B. Buccal
membrane
containing 1-
octanol
C. Body
fluids
containing
0.2M HCl
D. Protein
binding
containing 1-
octanol
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Before use, the aqueous phase
and 1-octanol were saturated with
each other.
Samples were withdrawn and
returned to compartment A with a
syringe.

40.  Consist of KC-Cell containing distilled water (50ml) at 370C as dissolution
medium
 TMDDS was placed in a glass tube fitted with a 10# sieve at the bottom which
reciprocate in the medium at 30 strokes per min.
40

41.  Animal used: dog, rabbits, rat, cat, hamster, pigs, and sheep
 RAT: The oesophagus is ligated to prevent absorption pathways other than oral
mucosa
 At different time intervals, the blood is withdrawn and analysed
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42. In the analysis of in vitro and in
vivo drug correlation, rapid
drug absorption may be
distinguished from the slower
drug absorption by observation
of the absorption time for the
dosage form. The quicker the
absorption of the drug the less
is the absorption time required
for the absorption of the certain
amount of the drug. The time
required for the absorption of
the same amount of drug from
the dosage form is correlated
Dissolution Rate Vs Absorption
Rate
If the dissolution rate is the limiting
step in the absorption of the drug,
and is absorbed completely after
dissolution, a linear correlation may
be obtained by comparing the
percent of the drug absorbed to the
percent of the drug dissolved. If the
rate limiting step in the
bioavailability of the drug is the
rate of absorption of the drug, a
change in the dissolution rate may
not be reflected in a change in the
rate and the extent of drug
absorption from the dosage form
Percent of Drug Dissolved Vs
Percent of Drug
Absorbed
It is expected that a poorly
formulated dosage form
releases amount of drug than
from a well formulated dosage
form, and, hence the amount of
drug available for absorption is
less for poorly formulated
dosage form than from a well
formulated dosage form.
% of drug dissolved In-vitro Vs
Peak plasma concentration

43.  MICROSPHERES IN VACCINE DELIVERY.
Eg ; Diphtheria toxoid , Tetanus toxoid.
 TARGETED DRUG DELIVERY.
Eg ; ocular, eye (cornea).etc
 CONTROLLED RELEASE.
Eg ; GI tumors, Bone tumors.
 CHEMOEMBOLIZATION.
 IMMUNO MICROSPHERES 43

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