MICROSPHERES &
MAGNETIC MICROSPHERES
PRESENTED BY GUIDED BY
K. Swapna Dr.Yasmin begam
256213886015 M.Pharm, Ph.D
CONTENTS
INTRODUCTION
CONCEPT
ADV AND DISADV
MATERIALS REQUIRED
IDEAL MICROSPHERE PREREQUISITES
METHOD OF PREPARATION
CHARACTERIZATION or EVALUATION
APPLICATIONS
2
CONCEPT
The Main Concept involved is :
Accurate Delivery of Small quantities of Potent Drug and
provide Controlled Release. .
Eg : Narcotics , Antagonist and Steroid hormones.
Selective and Effective Localization of pharmacologically active moiety at preselected target(s) in therapeutic concentration,,
Disable it’s Exposure to non-target normal tissues and cells.
3
ADVANTAGES :
SC, IM or Intraperitoneal administration
Biodegradable microspheres containing antigens will protect the antigens from the proteolysis
It is inexpensive (Encapsulation method)
Various degrees of controlled release can be achieved
More uniform effect of the drug
Reduction of drug Side Effects
Reduced fluctuation in circulating drug levels
Avoids hepatic first pass metabolism
4
DISADVANTAGES :
High molecular weight compounds have limited & restricted loading & their release may be difficult
Formation of complexes with the blood components
High cost
Productivity more difficult
Reduced ability to adjust the dose
Highly sophisticated technology
Requires skills to manufacture
Difficult to maintain stability of dosage form.
5
PREREQUISITES FOR IDEAL MICROSPHERES
Longer duration of Action
Control of Content Release
Increased Therapeutic Efficiency
Drug Protection
Reduction of Toxicity
Biocompatibility
Sterilizability
Relative Stability
Dispersability
Targetability
6
MATERIALS USED FOR THE PREPARATION
Natural materials Synthetic polymers
Proteins
Eg : Albumins , Gelatin
Non-biodegradable
Eg : Acrolein , Epoxy polymers
Carbohydrates
Eg : Starch , Agarose
Chemically Modified
Carbohydrates
Eg : Poly (Acryl)dextran ,
Poly(Acryl)starch
Biodegradable
Eg : Lactides and glycolides and their
copolymers
7
METHOD OF PREPARATION
Single Emulsion Technique
Double Emulsion Technique
Polymerization techniquesNormal polymerization
Interfacial polymerization
Coacervation technique
Spray Drying & Spray Congealing
Solvent Extraction
8
SINGLE EMULSION TECHNIQUE
Microparticulate carrier of natural polymers
are dissolved or dispersed in aqueous
medium followed by dispersion
The cross linking can be achieved either by
means of heat or by using the chemical cross
linkers like glutaraldehyde, formaldehyde,
butanol .
9
Aq solution/suspension of polymer
Dispersion in org phase oil/chloroform
Microspheres in org phase Microspheres in org phase
Cross linkingHeat/Denaturation Chemical
Micro spheres
Centrifugation, washing, separation
10
DOUBLE EMULSION TECHNIQUE
It involves the formation of the multiple emulsion of type w/o/w & is best suited for the water soluble drugs
A number of hydrophilic drugs like LH-RH agonists, vaccines, proteins or peptides & conventional molecules are successfully incorporated in to the microspheres using the method of double emulsion solvent evaporation or extraction
11
Aq sol of protein/polymer drug (if present)
Dispersed in Oil
First emulsion
Multiple emulsion
Micro spheres in solution
Micro spheres
Homogenization
Addition of aq sol of PVA
Addition to large aq phase(Denaturation)
Separation, washing, drying
12
POLYMERIZATION TECHNIQUES
Normal polymerization
Bulk polymerization,
Suspension precipitation and
Emulsion polymerization
Interfacial polymerization
13
BULK POLYMERIZATION
Monomer, Bioactive material, Initiator
Polymer Block
Microspheres
Polymerization
Mould/ mechanical fragmentation
14
SUSPENSION POLYMERIZATION
Monomer, Bioactive material, Initiator
Droplets
MICROSPHERES >100µM
Separation & drying
Vigorous agitation, heat
Dispersed in water & stabilizer
15
EMULSION POLYMERIZATION
Monomer/ bioactive material Aq sol of NaOH, initiator, surfactant
Micellar sol of polymer in aq medium
Microspheres formation
MICROSPHERES
Separation, washing, drying
polymerisation
Vigorous stirring
16
INTERFACIAL POLYMERIZATION
It involves reaction of various monomers at
the interface between the two immiscible
liquid phases to form a film of polymer
The continuous phase is generally aqueous
in nature throughout which the second
monomer is emulsified
The monomers present in either phase
diffuse rapidly & polymerize rapidly at the
interface.
17
COACERVATION TECHNIQUE
Aq/ org sol of polymer
Drug dispersed in polymer sol
Polymer rich globules
Microspheres in aq/ org phase
Microspheres
Phase separation
Hardening
Separation, drying
18
SPRAY DRYING AND SPRAY CONGEALING
Based on drying of the mist of the polymer and drug in the air
The polymer is first dissolved in a suitable volatile organic solvent
The drug in solid form is then dispersed in polymer solution under high speed homogenization;
It is then atomized in a stream of hot air.
19
CONT’D
Formation of the small droplets or fine mist
from which the solvent evaporates
instantaneously leading to formation of the
microspheres
Micro particles are separated from the hot air
by means of the cyclone separator and
traces of solvent are removed by vacuum
drying
20
SOLVENT EXTRACTION
Here microspheres are prepared by removal of the organic solvent with extraction with water
This process decreases the hardening time of microspheres
It depends on the temperature of water, ratio of emulsion volume to the water and the solubility profile of the polymer.
21
CHARACTERIZATION OF MICROSPHERES
Particle size and shape
Electron spectroscopy for chemical analysis
Attenuated total reflectance Fourier transform-infrared spectroscopy
Density determination
Isoelectric point
Surface carboxylic acid residue
Surface amino acid residue
Capture efficiency
Release studies
Angle of contact
22
Capture efficiency
% Entrapment = Actual content X100
Theoretical content
Density Measurement : By Using Multivolume Pychometer
Release Studies : By Two Methods:
a) Rotating Paddle Dissolution Apparatus
b) Dialysis Method
Media : Phosphate Saline Buffer at pH 7.4
Isoelectric Point : By Using Micro electrophoresis
Apparatus
23
In vitro drug release studies:
Microspheres of all batches had faster initial drug release approximately 25 percentages within 15 minutes. Then the release was slow and sustained over 8 hours, depending upon the polymer: drug ratio. By the end of 8th hour the percentage of drug release was found to 79.22, 84.72 and 94.12 for F1, F2 and F3 formulation respectively (figure 2). The formulation F3 showed better sustained release (94%) at the end of the 8th hour as compared to other batches. This may be due to better loading, encapsulation efficiency and increased particle size as compared to other batches.
24
APPLICATIONS
1] In Vaccine Delivery
2] In Case of Antigen Release
3] Targeting of Drug
4] ImmunoMicrospheres
5] MicroSponges : Topical porous Microspheres
6] Surface Modified Microspheres
7] Imaging
25
26
CONTENTS
1] INTRODUCTION
2] CONCEPT
3] IDEAL CHARACTERISTICS
4] MATERIALS CREATING MF
5] ADVANTAGES AND DISADVANTAGES
6] APPLICATIONS
27
INTRODUCTION
DEFINITION :
Magnetic Microspheres (MM):
These are microspheres, containing magneticsubstance inside which, can be easily targeted byapplying external magnetic field.
They were mainly developed to minimize renalclearance and to increase target site specificity. Thissystem has a great potential in the treatment oflocalized tumors in the regions of well-defined bloodsupply.
28
CONCEPT
1] Ideally, magnetic microspheres are injected and selectively a
and magnetically localized at the capillary level, they would
have free flow access through the large arteries.
2] The selective capillary localization of the microspheres can be
achieved by taking advantage of the physiological difference in the
linear flow velocity of blood at the capillary level (0.05 cm/sec).
Obviously, a much lower magnetic field strength is necessary to restrict
the microspheres at the slower moving flow velocities of blood in
capillaries.
After removal of the magnetic field, the microspheres stillcontinued to lodge at the target site, presumable because they had lodgedin the vascular endothelium, penetrated in to the interstitial space,resulting in their retention.
29
IMPORTANT CHARACTERISTICS
Particle size of a drug carrier can affect the degree of drug entrapment.
Increase in size of albumin microspheres due to hydration can alter its
distribution.
Use of sub micro size microspheres minimizes the incidence of pulmonary
embolism often encounter with particles greater than 7 microns or particles,
which aggregate upon their in vivo administration.
The retention of magnetic microspheres at the target site is dependent on the
magnetic content of the carrier and the magnitude of applied magnetic field.
In targeting, using MM, the magnetic content of the carrier and the magnitude
of applied magnetic field are important.
30
Note: Incorporation of drug and magnetic needs to
be delicately balanced. Depending on the
type of drug and the desired target site, the
optimum magnetic content would vary
between 20% and 50% magnetic by dry
weight of the drug carrier complex
retention..
31
MAGNETIC FIELD CREATORS MAGNETITE:
It is also called as ferric ferrous oxide, tri iron tetra oxide,and black iron oxide.
Magnetic iron oxide with chemical formula FeOfe203having a molecular weight of 231.55 with a chemicalcomposition of Fe=72.36%, O=27.64%.
The Ferro magnetic material when incorporated intomicrospheres makes them magnetically responsive, so thatthey can be concentrated to the desired site by applying someexternal magnetic field.
OTHER MF CREATORS ARE : ADRIAMYCIN,VINDESIN SULPHATE
32
ADVANTAGES :
Incorporation of magnetically responsive materials into microspheresmakes them susceptible to applied magnetic field, so that they areconcentrated to the target site by application of magnetic field externallyto that site. Due to this, rapid clearance of these microspheres by RES isprevented.
Microspheres can transit into extra vascular space creating an extravascular depot of drug for sustained release of drug within the targetedareas.
Increase of tumor targeting microspheres can be internalized by tumorcell due to its much-increased phagocytic activity as compared tonormal cell. So the problem of drug resistance due to inability of drugto be transported across the cell membrane can be prevented.
Controlled and predictable rate of drug release with smaller doses ofdrug can be achieved.
33
DISADVANTAGES
One of the major limitations of this system is, the drug cannotbe targeted to deep-seated organism in the body. This approachis confined to the targeting of drugs to the superficial tissueslike skin, superficial tumors or the joints.
Thrombosis at the site of administration.
The unknown toxicity of magnetic beads.
The possible unwanted localization of the product in the liverand the regions of RES and the dangerous effect of self-flocculation of the magnetic particles causing vascularobstruction to vital organs in the body.
34
APPLICATIONS
1] In Vaccine Delivery
2] In Case of Antigen Release
3] Targeting of Drug
4] ImmunoMicrospheres
5] MicroSponges : Topical porous Microspheres
6] Surface Modified Microspheres
7] Imaging
8] To Immobilize Enzymes
35
REFERENCE
• N.K JAIN Advances in controlled & Novel drug delivery, Pg No.12,177
• S.P. VYAS and Roop. K. KHAR, controlled drug delivery, concepts & Advances. Pg No.174, 176.
• www.ijprd.comInternational Journal of Pharma. Research and development. [ISSN 0974-9446].
• http://www.stumbleupon.com/su/AmpEKq/www.authorstream.com/Presentation/ksk121087-545436-microspheres
36
37
Top Related