micro drug delivery system for important for pharmacy students

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3.  Microspheres are small particles with diameters in the micrometer
range (typically 1µm to 1000µm). Microspheres are sometimes
referred to as microparticles.
 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 200µm.
 Microspheres are defined as Monolithic sphere or therapeutic agent
distributed throughout the matrix either as a molecular dispersion of
particles or can be defined as structure made up of continuous phase
of one or more miscible polymers in which drug particles are
dispersed at the molecular or macroscopic level.
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4. I. It should incorporate reasonably high concentrations of the drug.
II. Stability of the preparation after synthesis with acceptable shelf
life.
III. Controlled particle size and solubility in aqueous vehicles for
injection.
IV. Release of active pharmaceutical reagent with a good control over a
wide time scale.
V. Compatibility with a controllable biodegradability.
VI. Susceptible to chemical modification.
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5. I. Microspheres provide constant and prolonged therapeutic effect.
II. Reduces the dosing frequency and thereby improve the patient
compliance.
III.They could be injected into the body due to the spherical shape and
smaller size.
IV.Better drug utilization will improve the bioavailability and reduce the
incidence or intensity of adverse effects.
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6. I. The release rate of the controlled release dosage form may vary
from a variety of factors like food and the rate of transit though gut.
II. Differences in the release rate from one dose to another.
III.Controlled release formulations generally contain a higher drug
load and thus any loss of integrity of the release characteristics of
the dosage form may lead to potential toxicity.
IV.Dosage forms of this kind should not be crushed or chewed.
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7. I. For Taste and odour masking.
II. To delay the volatilization.
III. For Separation of incompatible substances.
IV. For Improvement of flow properties of powders.
V. To Increase the stability of the drug against the external
conditions.
VI.To Increase half life of drug.
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8. VII.For Safe handling of toxic substances.
VIII.To improve the solubility of water insoluble substances by
incorporating dispersion of such material in aqueous media.
IX. To reduce the dose dumping potential compared to large
implantable devices.
X. For conversion of oils and other liquids to solids for ease of
handling.
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9. 1. Bio adhesive microsphere
2. Magnetic microspheres
3. Floating microspheres
4. Radioactive microsphere
5. Polymeric microsphere
6. Mucoadhesive microspheres
Adhesion or sticking of drug to the membrane by using the
sticking property of the water soluble polymers. Adhesion of
microsphere to the mucosal membrane such as buccal, ocular, rectal,
nasal etc. can be termed as bio adhesion. Increase in contact time
produces better therapeutic action.
e.g. higher concentration of clonazepam can be achieved in brain by
using gelatin+ chitosan as bio adhesive polymer. 9

10. This localises the drug to the disease site. Larger amount of
freely circulating drug can be replaced by smaller amount of
magnetically targeted drug. Magnetic carriers receive magnetic
responses to a magnetic field from incorporated materials that are used
for magnetic microspheres are chitosan, dextran etc.
The different type are;
Are used to deliver chemotherapeutic agent to liver tumour.
used to distinguish bowel loops from other abdominal
structures by forming nano size particles supramagnetic iron oxides.
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11. residence and increases fluctuation in plasma concentration.
e.g. ketoprofen
Radio emobilisation therapy microspheres sized 10-30 nm
are of larger than capillaries and gets tapped in first capillary bed
when they come across. They are injected to the arteries that lead to
tumour of interest. The radioactive microspheres deliver high
radiation dose to the targeted areas and the different kinds of
radioactive microspheres are α emitters, β emitters, γ emitters.
The bulk density is less than the gastric fluid and so remains
buoyant in stomach. The drug is released slowly at the desired rate, if
the system is floating on gastric content and increases gastric
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12. Natural polymers like starch which are biodegradable, bio
compatible, and bio adhesive in nature are used in this. Biodegradable
polymers prolongs the residence time when contact with mucous
membrane due to its high degree of swelling property with aqueous
medium, results gel formation. The rate and extent of drug release is
controlled by concentration of polymer and the release pattern in a
sustained manner.
The synthetic polymeric microspheres are widely used in
clinical application, moreover that also used as bulking agent, fillers,
embolic particles, drug delivery vehicles etc. and proved to be safe and
biocompatible.
The different types of polymeric microspheres can be
classified as follows;
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13. Mucoadhesive microsphere prepared by different method was
evaluated for their mucoadhesive properties. Microspheres have the
potential to be used for targeted and controlled release drug delivery
but coupling of mucoadhesive properties to microspheres has
additional advantages such as efficient absorption, enhanced
bioavailability of the drugs due to a high surface to volume ratio, a
much more intimate contact with the mucus layer, specific targeting
of drugs to the absorption site. Mucoadhesive microspheres can be
tailored to adhere to any mucosal tissue including those found in
eye, nasal cavity, urinary and gastrointestinal tract, thus offering the
possibilities of localized as well as systemic controlled release of
drugs.
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14. A complete understanding of how and why certain macromolecules attach
to a mucus surface is not yet available, but a few steps involved in the process
are generally accepted, at least for solid systems. Several theories have been
proposed to explain the fundamental mechanism of adhesion (N.K. Jain, et.al.,
1997). A General Mechanism of Mucoadhesion Drug Delivery system is show
in Figure;
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15. POLYMER
Natural Synthetic
Carbohydrates Proteins Chemically Biodegradable Non-biodegradable
Modified polymer polymer
Agarose, albumin, poly dextran, lactides, PMMA,
Carrageenam collagen poly starch glycosides glycidyl methacrylate
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16. POLYMER MECHANISM
Modified starch, HPMC, Carbopol Slower release of drug
Ethyl cellulose Controlled release for longer period of
time
PLGA, Chitosan Vaccine delivery
Magnetic polystyrene microspheres Specific cell labeling
Chitosan coated PIGA microspheres Targeted drug delivery
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18. The micro particulate carriers of natural polymers i.e. those of
proteins and carbohydrates are prepared by single emulsion technique.
The natural polymers are dissolved/dispersed in aqueous medium
followed by dispersion in the non-aqueous medium e.g. oil. In the
second step of preparation cross-linking of dispersed globule is carried
out. The cross linking is achieved by two methods i.e. either by heat or
by means of chemical cross linking agents including glutaraldehyde,
formaldehyde, diacid chloride etc. 18

19.  This method involves the formation of the multiple emulsion or
double emulsion of type w/o/w. It is best suited to water soluble
drugs, peptides, proteins and vaccines.
 This method can be used with both the natural as well as the
synthetic polymers.
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20.  Emulsion is then subjected to solvent removal either by solvent
evaporation or by solvent extraction process. The solvent
evaporation is carried out by maintaining emulsion at reduced
pressure or by stirring the emulsion so that the organic phase
evaporates out.
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21.  The emulsion is then added to large quantity of water into
which organic phase diffuses out. The solid microspheres are
subsequently obtained by filtration and washing with n-
hexane, acetone or any organic solvent to remove traces of oil
from the surface.
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22. a) Normal polymerization
b) Interfacial polymerization
Normal polymerization
 In bulk polymerization a monomer or a mixture of monomers
along with the initiator or catalyst is usually heated to initiate
polymerization. Polymer so obtained may be moulded as
microspheres.
 Suspension polymerization also referred as bead or pearl
polymerization. Here it is carried out by heating the monomer
or mixture of monomers as droplets dispersion in a continuous
aqueous phase. The droplets may also contain an initiator and
other additives.
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23.  Emulsion polymerization differs from suspension
polymerization as due to the presence initiator in the aqueous
phase which later on diffuses to the surface of micelles. Bulk
polymerization has an advantage of formation of pure
polymers.
Interfacial polymerization
 It involves the reaction of various monomers at the interface
between the two immiscible liquid phases to form a film of
polymer that essentially envelops the dispersed phase. In this
technique two reacting monomers are employed one of which
is dissolved in the continuous phase while the other being
dispersed in the continuous phase.
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24.  This process is based on the
principle of decreasing the
solubility of the polymer in
organic phase to affect the
formation of polymer rich
phase called the coacervates.
In this method, the drug particles are dispersed in a solution of the
polymer and an incompatible polymer is added to the system
which makes first polymer to phase separate and engulf the drug
particles. Addition of non-solvent results in the solidification of
polymer.
e.g. Poly lactic acid (PLA) microspheres have been prepared by
this method by using butadiene as incompatible polymer.
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25.  The polymer is first dissolved in a suitable volatile organic solvent
such as dichloromethane, acetone etc.
 The drug in the solid form is then dispersed in the polymer
solution under high speed homogenisation. This dispersion is then
atomised in a stream of hot air.
 The atomisation leads to the formation of small droplets or the fine
mist from which the solvent evaporates instantaneously leading
the formation of microspheres.
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26.  Solvent extraction method is
used for the preparation of
the micro particles involves
removal of the organic
phase by extraction of the
organic solvent.
 This process decreases the hardening time for the microspheres.
The process involves direct addition of the drug or protein to
polymer organic solution.
 The rate of solvent removal by extraction method depends on the
temperature of water, ratio of emulsion volume to the water and
the solubility profile of the polymer.
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27.  The processes are carried out in a liquid manufacturing vehicle. The
microcapsule coating is dispersed in a volatile solvent which is immiscible with
the liquid manufacturing vehicle phase. A core material to be microencapsulated
is dissolved or dispersed in the coating polymer solution.
 With agitation the core material mixture is dispersed in the liquid manufacturing
vehicle phase to obtain the appropriate size microcapsule. The mixture is then
heated if necessary to evaporate the solvent for the polymer of the core material
is disperse in the polymer solution, polymer shrinks around the core. If the core
material is dissolved in the coating polymer solution, matrix – type microcapsules
are formed. 27

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29. Microsphere (50 mg) was suspended in distilled water (5mL)
containing 2%w/v of tween 80. To prevent microsphere
aggregation the above suspension is sonicated in water bath and
the particle size was expressed as volume mean diameter in
micrometer.
This method was used to determine particle size by using
optical microscope (Meizer OPTIK). The measurement was done
under 450x (10x eye piece and 45x objective) and100 particles
were calculated.
The polyelectrolyte shell was prepared by incorporating
chitosan of different molecular weight into the W2 phase and the
resulting particles were determined by zeta potential measurement.
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30. Surface morphology was determined by the method SEM.
In this microcapsule were mounted directly on the SEM sample
slub with the help of double sided sticking tape and coated with
gold film under reduced pressure. The SEM imaging can be used
to check whether the product is successfully prepared as desired.
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31. Different solution (100mL) were taken such as (distilled
water, buffer solution of pH(1.2, 4.5, 7.4) were taken and
microspheres (100mg) were placed in a wire basket and kept on
the above solution and swelling was allowed at 37oC and changes
in weight variation between initial weight of microspheres and
Microspheres containing of drug (5mg) were crushed and
then dissolved in distilled water with the help of ultrasonic stirrer
for 3 hour and was filtered then assayed by UV-visible
spectroscopy. Entrapment efficiency is equal to ratio of actual drug
content to theoretical drug content.
weight due to swelling was measured by taking weight
periodically and soaking with filter paper.
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32. Scan speed - 40/min
Scintillation detector
Primary silt=1mm
Secondary silt=0.6 mm.
Thermal analysis of microcapsule and its component can be
done by using-
• Differential scanning calorimetry (DSC)
• Thermo gravimetric analysis (TGA)
• Differential thermometric analysis (DTA)
Change in crystalinity of drug can be determined by this
technique. Micro particles and its individual components were
analysed with the help of D & discover (Bruker, Germany). Scanning
range angle between 80C - 700C.
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33. By placing the microspheres in screw capped glass container
and stored them at following conditions:
1. Ambient humid condition
2. Room temperature (27+/-2 0C)
3. Oven temperature (40+/-2 0C)
4. Refrigerator (5 0C-80C).
It was carried out of a 60 days and the drug content of the
microsphere was analysed.
The drug polymer interaction and also degradation of drug
while processing for microencapsulation can be determined by
FTIR.
Accurately the sample was weighed and heated on alumina
pan at constant rate of 10oC/min under nitrogen flow of 40 ml/min.
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34. It has been observed that microspheres are better choice of drug
delivery system than many other types of drug delivery system
because it is having the advantage of target specificity and better
patient compliance. Its applications are enormous as they are not only
used for delivering drugs but also for imaging tumours, detecting bio
molecular interaction etc. So in future microspheres will have an
important role to play in the advancement of medicinal field. In
future by combining various other strategies, microspheres will find
the central place in novel drug delivery, particularly in diseased cell
sorting, diagnostics, gene & genetic materials, safe, targeted and
effective in vivo delivery.
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