microsphere as drug delivery system

20SSRMPH06 SSR COLLEGE OF PHARMACY,SILVASSA JIDNESH DHARMAMEHER
SEMINAR ON :
“SALIENT PRESPECTIVES OF MICROSPHERE AS
A NOVEL DRUG DELIVERY SYSTEM”

PRESENTATION OUTLINE
 INTRODUCTION
 NEEDS OF MICROSPHERES
 IDEAL CHARACTERISTICS
 ADVANTAGES AND DISADVANTAGES
 TYPES OF MICROSPHERES
 MATERIAL USED IN PREPARATION
 METHODS OF PREPARATION
 EVALUATION
 APPLICATION AND MARKETED FORMULATION

INTRODUCTION
 Microspheres are multiparticulate drug delivery systems which
are prepared to obtain prolonged or controlled drug delivery to
improve bioavailability, stability and to target the drug to specific
site at a predetermined rate.
 Microspheres are small spherical particles, with diameters 1 μm
to 1000 μm. They are spherical free flowing particles consisting
of proteins or synthetic polymers which are biodegradable in
nature.
 Microspheres can be manufactured from various natural and
synthetic materials. Microsphere play an important role to
improve bioavailability of conventional drugs and minimizing
side effects.

Contd…
• There are three types of micropaerticulates:
MICROPARTICULATES
MICROCAPSULES
MICROMATRICES
polynuclear

NEEDS OF MICROSPHERES
 Targeting of active drug moieties to specific body sites with
controlled and predetermined drug release from the drug delivery
systems have great impact on human health care.
 Novel drug delivery technology provides an effective approach for
entrapment of therapeutically active drugs in multiple unit dosage
forms such as microparticles and nanoparticles etc, which transforms
the absorption and kinetic properties of the drug molecules.
 Among multiple unit dosage forms microspheres plays an important
role in arena of particulate type of drug delivery systems due to
better entrapment, small size with good release characteristics.
 These systems are coupled with various advantages such as
improved therapeutic efficacy with better compliance, encapsulation
of variety of drug molecules (macro and micromolecules) low toxicity
in comparison to conventional dosage forms.
Microspheres an innovative approach in drug delivery system,solanki

IDEAL CHARACTERISTICS
 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.

ADVANTAGES
 These systems provide prolonged and constant therapeutic effect.
 Reduces the dosing frequency and therefore improvement in patient compliance.
 Microspheres produce more reproducible drug absorption.
 Drug discharge in stomach is hindered and that’s why local unwanted effects are reduced.
 In case of microspheres, better therapeutic effect for short half-life of drugs can be achieved.
 Dose dumping effect can be reduced by microspheres.
 Microspheres also reduce the chances of G.I. irritation.
 Microspheres provide freedom from drug and recipients incompatibilities especially with
buffer.
 Better protection of drugs against environment conditions.
 Taste and odour of unpleasant drugs can be effectively masked.
 Microspheres reduce the first pass metabolism.
 Microspheres can be easily injected in body because of their small and spherical size.
 Microspheres enhance the biological half-life and also improve the bioavailability.

DISADVANTAGES
 The costs of the materials and processing of the controlled release
preparation, are substantially higher than those of standard
formulations.
 The fate of polymer matrix and its effect on the environment.
 The fate of polymer additives such as plasticizers, stabilizers,
antioxidants and fillers.
 Reproducibility is less.
 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.

METHODS OF PREPARATION
• Solvent evaporation
• Hot melt microencapsulation
• Solvent extraction
• Hydrogel microspheres
• Spray drying
• Phase inversion
• Alkaline co-precipitation
• Inverse phase sepration polymerization
• Sono chemical
• Spray cooling/chilling
• Pan coating
J.K. Vasir et al.

• Solvent evaporation:
 It is the most extensively used method of microencapsulation, first
described by Ogawa et al. (1988).
 A buffered or plain aqueous solution of the drug (may contain a
viscosity building or stabilising agent) is added to an organic phase
consisting of the polymer solution in solvents like dichloromethane
(or ethyl acetate or chloroform) with vigorous stirring to form the
primary water in oil emulsion.
 This emulsion is then added to a large volume of water containing an
emulsifier like PVA or PVP to form the multiple emulsion (w/o/w).
 The double emulsion, so formed, is then subjected to stirring until
most of the organic solvent evaporates, leaving solid microspheres.
The microspheres can then be washed, centrifuged and lyophilised to
obtain the free flowing and dried microspheres.

• Solvent evaporation:

Hot melt microencapsulation:
 This method was first used by Mathiowitz and Langer (1987) to
prepare microspheres of polyanhydride copolymer of poly[bis(p-
carboxy phenoxy) propane anhydride] with sebacic acid.
 In this method, the polymer is first melted and then mixed with solid
particles of the drug that have been sieved to less than 50µm.
 The mixture is suspended in a non-miscible solvent (like silicone oil),
continuously stirred, and heated to 5◦C above the melting point of
the polymer. Once the emulsion is stabilised, it is cooled until the
polymer particles solidify.
 The resulting microspheres are washed by decantation with
petroleum ether.

Hot melt microencapsulation:
 The primary objective for developing this method is to develop a
microencapsulation process suitable for the water labile
polymers, e.g. polyanhydrides.
 Microspheres with diameter of 1–1000 µm can be obtained and
the size distribution can be easily controlled by altering the
stirring rate.
 The only disadvantage of this method is the moderate
temperature towhich drug is exposed.

Solvent extraction:
 It is a non-aqueous method of microencapsulation, particularly
suitable for water labile polymers such as the polyanhydrides.
 In this method, drug is dispersed or dissolved in a solution of the
selected polymer in a volatile organic solvent like methylene chloride.
 This mixture is then suspended in silicone oil containing Span 85 and
methylene chloride.
 After pouring the polymer solution into silicone oil, petroleum ether
is added and stirred until solvent is extracted into the oil solution. The
resulting microspheres can then be dried in vacuum.

Solvent extraction:

HYDROGEL MICROSPHERE:
 Microspheres made of gel-type polymers, such as alginate, are
produced by dissolving the polymer in an aqueous solution,
suspending the active ingredient in the mixture and extruding
through a precision device, producing microdroplets which fall into a
hardening bath, that is slowly stirred.
 The hardening bath usually contains calcium chloride solution,
whereby the divalent calcium ions crosslink the polymer forming
gelled microspheres. The method involves an all-aqueous” system
and avoids residual solvents in microspheres.
 The surface of these microspheres can be further modified by coating
them with polycationic polymers, like polylysine after fabrication. The
particle size of microspheres can be controlled by using various size
extruders or by varying the polymer solution flow rates.

HYDROGEL MICROSPHERE:

SPRAY DRYING:
 This was used to prepare polymeric blended microsphere loaded with
drug.
 It involves dispersing the core material into liquefied coating material
and then spraying the mixture in the environment for solidification of
coating followed by rapid evaporation of solvent.
 Organic solution of poly (epsilon-caprolactone) (PCL) and cellulose
acetate butyrate (CAB), in different weight ratios and drug were
prepared and sprayed in different experimental condition achieving
drug loaded microspheres.
• The quality of spray-dried microspheres can be improved by the
addition of plasticizers, e.g. citric acid, which promote polymer
coalescence on the drug particles and hence promote the formation
of spherical and smooth surfaced microspheres.

SPRAY DRYING:
 The size of microspheres can be controlled by the rate of spraying,
the feed rate of polymer drug solution, nozzle size, and the drying
temperature.
 This method of microencapsulation is particularly less dependent on
the solubility characteristics of the drug and polymer and is simple,
reproducible, and easy to scale up
 It is widely used method for preparation of the microspheres.

SPRAY DRYING:

PHASE INVERSION MICROENCAPSULATION:
 The process involves addition of drug to a dilute solution of the
polymer (usually 1–5%, w/v in methylene chloride).
 The mixture is poured into an unstirred bath of a strong non-solvent
(petroleum ether) in a solvent to non-solvent ratio of 1:100, resulting
in the spontaneous production of microspheres through phase
inversion.
 The microsphere in the size range of 0.5–5.0 m can then be filtered,
washed with petroleum ether and dried with air.
 This simple and fast process of microencapsulation involves relatively
little loss of polymer and drug.

PHASE INVERSION MICROENCAPSULATION:

ALKALINE CO-PRECIPITATION:
 Treat poly (acrylic acid–divinylbenzene) microspheres with dilute
aqueous NaOH solution (0.5 M) for hours at suitable temperature to
transform the carboxylic acid groups to sodium carboxylates and then
washed thoroughly with water to remove the excess NaOH till neutral
pH.
• Purged the microsphere suspension with nitrogen for 30 min. To this
suspension add an aqueous solution of FeCl3 and FeCl2 that had been
purged with nitrogen.
• Stirred the mixture overnight under nitrogen atmosphere for ion
exchange.

 The resulting microspheres were washed repeatedly with water
under nitrogen atmosphere to remove excess iron salts.
 Added drop wise an aqueous NaOH solution (3 M) to a suspension of
the microspheres taken up with iron ions under nitrogen atmosphere
to adjust the pH value to be >12. The mixture was then heated to 60
°C and kept for another 2 h.
 The resulting magnetic microspheres were suspended in an aqueous
HCl solution (0.1 M) to transform the –COONa to –COOH, and then
washed thoroughly with water to neutral pH, dried under vacuum at
50 °C overnight, giving magnetic microspheres.

INVERSE PHASE SUSPENSION POLYMERIZATION:
 A 250 mL three-neck flask fitted with a mechanical stirrer used for
performing the reaction.
 Continuous phase includes: 100 mL of castor oil and 10 mL of span
80. Determined amount of itaconic acid (IA), Styrene (St),
divinylbenzene (DVB) and N, N_ Methylene-bisacrylamide (BIS)
dissolved completely in DMSO, and the organic phase was added
drop wisely into the flask, with 70 °C heating using an oil bath.
 Ammonium persulfate (INITIATOR) added The reaction proceeded for
8 h with continuous stirring. The resulting microspheres were
separated by centrifugation. Further washed with diethyl ether and
then by deionized water.

SONOCHEMICAL METHOD:
 Decane and iron pentacarbonyl Fe(CO)5 were layered over a 5% w/v
protein solution(BSA).
 The bottom of the high-intensity ultrasonic horn was positioned at
the aqueous organic interface.
 The mixture was irradiated for 3 min, employing a power of W150 W/
32cm with the initial temperature of 23 °C in the reaction cell. The pH
was adjusted to 7.0 by adding HCl.
 This procedure was performed again with an aqueous solution of iron
acetate, Fe(CH3CO2)2.

SONOCHEMICAL METHOD:
 After the synthesis, the products were separated from the unreacted
protein and from the residues of iron acetate or iron pentacarbonyl
by centrifugation (1 000 r/min for 5 min).
 The magnetic microspheres were washed a few times with sufficient
volumes of water to remove the residues
.

• Spray Cooling/ Chilling:
 Spray cooling/chilling is the least expensive encapsulation
technology.
 It is used for the encapsulation of organic and inorganic salts,
textural ingredients, enzymes, flavors and other functional
ingredients.
 It improves heat stability, delay release in wet environments,
and/or convert liquid hydrophilic ingredient into free flowing
powders.
 Spray cooling/chilling is typically referred to as ‘matrix’
encapsulation because the particles are more adequately
described as aggregates of active ingredient particles buried in
the fat matrix.

SPRAY COOLING

PAN COATING
1. Solid particles are mixed with a dry coating
material.
2. The temperature is raised so that the coating
material melts and encloses
3. the core particles, and then is solidified by
cooling.

PAN COATING
Or,
the coating material can be gradually applied to
core particles tumbling in a vessel rather than
being wholly mixed with the core particles from
the start of encapsulation.
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PAN COATING
The particles are tumbled in a pan or
other device while the coating
material is applied slowly
 The coating is applied as a solution
or as an atomized spray to the
desired solid core material in the
coating pan
 Usually, to remove the coating
solvent, warm air is passed over the
coated materials as the coatings are
being applied in the coating pans.
 In some cases, final solvent removal
is accomplished in drying oven.

Different methods and polymers
.
Process used Polymers
Comments
Particle size
(µm)
Polymers used
Solvent evaporation 1-100 Relatively stable polymers,
e.g.
polyesters, polystyrene
Hot melt
microencapsulation
1-1000 Water labile polymers, e.g.
polyanhydrides,
polyesters;
with a molecular weight of
1000-50000
Solvent removal 1-300 High melting point
polymers
especially polyanhydrides
Spray drying 1-10 Polylactide (PLA) and
polylactide-co-glycolide
(PLGA) were mostly used
Phase inversion 0.5-5 Chitosan, CMC,
alginate,polyanhydride
J.K.
Vasir
et al

• CORE MATERIAL:
It is a specific material to be coated which can be solid/liquid.
Liquid core: oil,dispersion,solution.
Solid core: API, stabilizer,diluent or any excipient.
• Coating material:
It is material which can form film or envolope around core
material.
MATERIALS USED IN PRPARATION OF MICROSPHERES

 It should be capable of forming film which is
cohesive with core material.
Material should be satisfy product objective and
reuirement.
Best suited for the method of encapsulation.
SELECTION CRITERIA FOR COATING MATERIAL

1. Stabilization of core material.
2. Inert toward active ingredients.
3. Controlled release under specific conditions.
4. Film-forming, pliable, tasteless, stable.
5. Non-hygroscopic, no high viscosity, economical.
6. Soluble in an aqueous media or solvent, or
melting.
7. The coating can be flexible, brittle, hard, thin etc.
IDEAL PROPRTIES FOR COATING MATERIAL
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Classification of polymers
POLYMERS
SYNTHETIC NATURAL
Non
biodegra
dable
biodegradable
CARBOHYDRATES
PROTEIN
Chemically
modified
carbohydrates

Material used Types Examples
Synthetic polymers a) Biodegradable
b) Non biodegradable
Glycosides,epoxy polymer
Poly
anhydride,lacticides,acrotein,glycidyl
methylacryl
Natural a) Carbohydrates
b) Protein
c) Chemically modified
carbohydrate
Agarose,starch,chitosan etc.
Gelatin,albumin,collagen etc.
Polydextran,polystarch etc.
Satinder Kakar et al.

TYPES OF MICROSPHERES
MICROSPHERES
BIOADHESIVE
MAGNETIC
DIAGNOSTIC
THERAPEUTIC
FLOATING
raadioactive

1.BIOADHESIVE MICROSPHERES:
 Bioadhesive microspheres include microparticles and microcapsules
(having a core of the drug) of 1–1000µm in diameter and consisting
either entirely of a bioadhesive polymer or having an outer coating of
it, respectively.
 Microspheres, in general, have the potential to be used for targeted
and controlled release drug delivery; but coupling of bioadhesive
properties to microspheres has additional advantages, e.g. efficient
absorption and 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
achieved by anchoring plant lectins, bacterial adhesins and
antibodies, etc. on the surface of the microspheres.
.

 Bioadhesive 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 localised as
well as systemic controlled release of drugs.
.

 The specific mucosal surfaces can be targeted using site-specific
chemical agents that are anchored onto the polymeric DDS. The first
generation mucoadhesive polymers lack specificity and can bind to
any mucosal surface.
.

No Glycosyl groups on
cell membranes
Specific ligands Specific site
1 Mannose Galanthus nivalis
agglutinin (GNA)
Epithelial cells in stomach,
caecum, and colon
2 N-Acetyl glucosamine Wheat germ
agglutinin (WGA)
Epithelial cells in stomach,
caecum, colon and
absorptive enterocytes in small
intestine
3 N-Acetyl
galactosamine
Lectin ML-1 from
Viscum album
Endocytosed by villus enterocytes
and goblet cells
Strong binding to epithelial cells in
small intestine
4 Fucose Aleuria aurentia
agglutinin (AAA)
Specific binding and transcytosis
by M cells
J.K. Vasir et al.

Some mechanism involved in bioadhesion:
1.electrostatic force of attraction.
2. adsorption – Surface forces resulting in chemical bonding.
3. wetting: Ability of bioadhesive polymers to spread and develop
intimate contact with the mucus membranes.
4. Diffusion theory: Physical entanglement of mucin strands and the
flexible polymer chains.
J.K. Vasir et al.

• Methods of preparation:
 Solvent evaporation
 Hot melt microencapsulation
 Solvent extraction
 Hydrogel microspheres
 Spray drying
 Phase inversion

• APPLICATIONS:
DRUG ROUTE OF ADMINISTRATION POLYMER USED COMMENTS
ACYCLOVIR Ocular Chitosan Slow release rate and increase AUC
Methyl prednisolone Ocular Hyaluronic acid Slow release rates
Sustained drug concentration in tear fluids
Gentamicin Nasal DSM + LPC Increased nasal absorption
Insulin Nasal DSM + LPC Efficient delivery of insulin into the
systemic
circulation via nasal route
Amoxicillin GI AD-MMS (PGEFs) Greater anti H. pylori activity
Riboflavin GI AD-MMS (PGEFs) Higher AUC
Effective absorption from the absorption
window
Nerve growth factor
(nGF)
Vaginal HYAFF Increased absorption from HYAFF microspheres
Vancomycin Colonic PGEF coated with Eudragit
S 100
Well absorbed even without absorption
enhancers
Insulin Colonic PGEF coated with Eudragit
S 100
Absorbed only in the presence of absorption
enhancers, e.g. EDTA salts
J.K.
Vasir
et
al.

2.MAGNETIC MICROSPHERES:
• Magnetic drug delivery by particulate carriers is an efficient method
of drug delivery to a localized disease site.
• A drug or therapeutic radioisotope is encapsulated in a magnetic
compound; injected into patient’s blood stream & then stopped with
a powerful magnetic field in the target area.
• Drug targeting is a specific form of drug delivery where the drug is
directed to its site action or absorption.

Two different types of magnetic microspheres:
1. Therapeutic magnetic microspheres:
It is used to deliver chemotherapeutic agent to liver tumor. Drugs like
proteins and peptides can also be targeted through this system.
2. Diagnostic magnetic microspheres:
It can be used for imaging liver metastases and also can be used to
distinguish bowel loops from other abdominal structures by forming
nano size particles supramagnetic iron oxides.

MAGNETIC MICROSPHERE
Representation of systemic drug delivery and magnetic drug delivery

MAGNETIC MICROSPHERE
Magnetic drug targeting.

Material used in preparation of magnetic microspheres:

• Methods of preparation:
• Phase inversion
• Alkaline co-precipitation
• Inverse phase sepration polymerization
• Sono chemical
MAGNETIC MICROSPHERES

• APPLICATIONS:
MAGNETIC MICROSPHERES
No Application Carrier/drug
1 Tumor targeting Mitoxantrone, Paclitaxel
2 Radioembolisation of liver and spleen tumors 186re/188re-glass
Microspheres
3 Magnetic bioseparation Dynabeads, used in
isolation of mRNA, genomic
DNA and proteins
4 Bacteria detection Streptavidin coated
magnetic beads
5 Contraceptive drug delivery Drug delivery is designed to
change in steroid secretion
during menstrual cycle.

 Floating microspheres are gastro-retentive drug delivery
systems based on non-effervescent approach.
 Hollow microspheres are in strict sense, spherical empty
particles without core.
 These microspheres are characteristically free flowing
powders consisting of proteins or synthetic polymers,
ideally having a size less than 200 μm.
 Due to its small particle size, these are widely distributed
throughout the gastrointestinal tract which improves drug
absorption and reduces side effects due to localized buildup
of irritating drugs against the gastrointestinal mucosa.
FLOATING MICROSPHERES

METHODS OF PREPARATION:
• Solvent evaporation
• Co-acervation phase sepration
• Ionotropic gelation method

POLYMER USED AND ITS APPLICATION:
DRUG ROUTE OF
ADMINISTRATION
POLYMER USED USE
Amoxicillin GI Ethyl cellulose-Carbopol-
934P
Greater anti H. pylori
activity
Delapril HCl GI Polyglycerol esters of fatty
acids (PGEFs)
MRT of drug is increased
Glipizide GI Chitosan Prolonged blood glucose
reduction
Glipizide GI Chitosan-alginate Prolonged blood glucose
reduction
Furosemide GI Polyglycerol esters of fatty
acids (PGEFs)
Increased bioavailability
Higher AUC
effective absorption from
the absorption
window.
www.globalresearchonline.net

 Radio embolization therapy microspheres sized 10-30 nm are of
larger than the diameter of the capillaries and gets tapped in first
capillary bed when they come across.
 They are injected in the arteries that leads them to tumour of interest
so all these conditions radioactive microspheres deliver high radiation
dose to the targeted areas without damaging the normal surrounding
the targeted areas without damaging the normal surrounding tissue.
 It differs from drug delivery system, as radio activity is not released
from microspheres but acts from within a radioisotope typical
distance and the different kinds of radioactive microspheres are α
emitters, β emitters, γ emitters.
 The effective treatment range in tissue is up to about 90 μm (10 cell
layers) for α -emitters, never more than 12 mm for β-emitters
and up to several centimetres for γ -emitters.
RADIOACTIVE MICROSPHERES
M. De Cuyper and J.W.M. Bulte

METHOD OF PREPARATION:
RADIOLABELING DURING THE MICROSPHERE PREPARATION:
Method of Labelling Examples
Colloid precipitation 99mTc sulphur colloid, 113mIn ferric hydroxide colloids,
165Dy-FHMA (~5 μm),
Isotope exchange 14C-, 35S- and 3H-labeling
Lipophilic inclusion 186Re/1 88Re-triphenylphosphine-liposomes
In situ production 99mTc-Buckminster fullerenes (C60 or C80) or aggregates
thereof (Technegas)

METHOD OF PREPARATION:
RADIOLABELING AFTER THE MICROSPHERE PREPARATION:
Method of Labelling Examples
Radiolabelling by ion
exchange
Anion- and cation-exchange resins:
BioRex 70 loaded with 90Y
Dowex 1-X4 loaded with 99mTcO4-
Dowex I-X8 loadedwith 56CrO4
Affinity to microsphere
material
153Sm-citrate bound to hydroxyapatite
microspheres
Reduction to insoluble,
colloidal compounds
99mTc-Sn PLA microspheres

APPLICATIONS:
DIAGNOSTIC APPLICATIONS:
Application Type of radioactive
microspheres used
Particle size
Infection localisation 111In-labeled leukocytes
111In-labeled liposomes
99mTc-labeled liposomes
99mTc-albumin
nanocolloid
12-20 μm
20 nm-1 μm
20 nm-1 μm
<80 nm
Tumour imaging 99mTc-labeled liposomes
67Ga-NTA
20 nm- 1 μm
65 nm
Gastrointestinal transit
studies
99m Tc-sulfur colloid 0.05-0.6 μm

APPLICATIONS:
THERAPEUTICS APPLICATIONS:
Application Type of radioactive
microspheres used
Particle size
Local radiotherapy 90Y-labeled poly(lactic
acid)
165Dy-acetylacetone
poly(lactic acid)
1-5 or 10-50 µm
1-5 or 10-50 µm
Intracavitary treatment
(peritoneal ovarian
tumour, metastases, cystic
brain tumour)
chromic 32P-phosphate
90Y-silicate, 90Y-citrate
198Au suspensions
1-2 μm
0.01-1 μm
5-25 nm

• Particle size and shape:
Method used:
light microscopy:
 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.
EVALUATION
Alagusundaram.M. et al /Int.J. ChemTech
Res.2009,1(3)

• Particle size and shape:
Method used:
Scanning electron microscopy:
SEM provides higher resolution in contrast to the
LM. 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.
EVALUTION

Electron spectroscopy for chemical analysis:
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.
EVALUTION

• Infrared Spectroscopy:
FT-IR is used to determine the degradation of the
polymeric matrix of the carrier system. The surface of the
microspheres is investigated measuring alternated total
reflectance (ATR). The IR beam passing through the
ATR cell reflected many times through the sample to
provide IR spectra mainly of surface material. The ATRFTIR
provides information about the surface composition
of the microspheres depending upon manufacturing
procedures and conditions.
EVALUTION

• DENSITY DETERMINATION:
 Using multivolume pycnometer.
 Helium is exposed and allowed for expansion.
 Two consecutive readings of reduction in pressure at different
initial pressure are noted.
 From two pressure readings the volume and hence the density of the
microsphere carrier is determined.
EVALUTION

Solid state by DSC/XRD:
 This test is done to find out the solid state property of the
drug and polymers used in the prparation of the
microspheres.
EVALUTION
DSC
XRD
Satinder Kakar et al.

• Isoelectric point:
 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.
 By using this data the electrical mobility of the particle can
be determined.
EVALUTION
Alagusundaram.M. et al /Int.J. ChemTech
Res.2009,1(3)

• Capture efficiency:
Encapsulation efficiency was calculated using the formula:
Encapsulation efficiency =
(Actual Drug Content / Theoretical Drug Content) ×100
• Estimation of Drug Content:
Weight equivalent to drug is measure and then analysis is
done by uv spectroscopic method.
EVALUTION

IN VITRO DISSOLUTION :
BEAKER METHOD:
 The dosage form in this method is made to adhere at the bottom of
the beaker containing the medium and stirred uniformly using over
head stirrer. Volume of the medium used in the literature for the
studies varies from 50-500 ml and the stirrer speed form 60-300 rpm.
Modified Keshary Chien Cell:
 It comprised of a Keshary Chien cell containing distilled water (50ml)
at 370 C as dissolution medium. TMDDS (Trans Membrane Drug
Delivery System) was placed in a glass tube fitted with a 10# sieve at
the bottom which reciprocated in the medium at 30 strokes per min.
EVALUTION

IN VITRO DISSOLUTION :
• Dissolution apparatus:
 Standard USP or BP dissolution apparatus have been used
to study in vitro release profiles using both rotating
elements, paddle and basket Dissolution medium used for
the study varied from 100- 500 ml and speed of rotation
from 50-100 rpm.
EVALUTION

 Ophthalmic Drug Delivery
 Oral drug delivery
 Gene delivery
 Nasal drug delivery
 Intratumoral and local drug delivery
 Buccal drug delivery
 Gastrointestinal drug delivery
 Transdermal drug delivery
 Colonic drug delivery
 Vaginal drug delivery
 Targeting by using microparticulate carriers
 Cosmetics
APPLICATIONS
Kadam N. R. and Suvarna V.:

FDA Approved products
Vivian Saez et al.

FDA Approved products
• Rykindo is approved by USFDA in march 2019
• Recently it is launched by Luye pharma in china
in the month of march 2021.
Alzhimer
disease
https://www.luye.cn/lvye_en/view.php?id=1890

MARKETED FORMULATIONS
Drug Commercial Name Company Technology
Risperidone RISPERDAL®
CONSTA®
Janssen®/Alkerme
s
Double emulsion
(oil in water)
Naltrexone Vivitrol Alkermes Double emulsion
(oil in water)
Leuprolide Trenantone® Takeda Double emulsion
(oil in water)
Octreotide Sandostatin® LAR Novartis Phase separation
Minocycline Arestin® Orapharma -
Triptorelin Trelstar™ depot Pfizer Phase separation
Lanreotide Somatuline® LA Ipsen-Beafour Phase separation
Bromocriptine Parlodel LAR ™ Novartis Spray drying
https://www.researchgate.net/publication/281405531_MICROSPHERES_A_RECENT_UP
DATE/download

OXYBENZONONE
SUNSCREEN

PATENTS
No Patent No. Drug used
1 CN 201110142359 Ketoprofen
2 CN 201110313846 Paclitaxel
3 CN 201210025085 5-fluorouracil
4 US08455091 Ganciclovir
5 EP19980924438 Cimetidine
6 EP20070808011 Risperidone
7 CA 2217462 Cyclosporin
8 CA 2579533 Irinotecan
9 DE1999609777 Levonorgesterel
10 DE1994632867 Doxorubicin
https://w
ww.resea
rchgate.n
et/figure
/Patents-
of-
Microsph
eres_tbl2
_281405
531

PATENTS
J.K. Vasir et al.

RECENT ADVANCEMENT
Verma et al

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 and
supplements as miniature versions of diseased
organ and tissues in the body.
FUTURE APPROACH

 Microspheres have been appeared as effective controlled release
dosage forms and represents great pharmaceutical applications in
area of drug delivery technology with multidisciplinary
advancements for treatment of number of diseases.
 Microspheres because of their attractive properties in terms of
patient compliance, therapeutic efficacy, and reduction in side
effects these delivery systems provide various therapeutic
benefits over conventional dosage forms. There is further place
for improvement in future in microsphere drug delivery systems
for more therapeutic results.
 Combination of microparticles with different novel strategies
particularly in diagnostic area, diseased cell sorting, entrapment
of genetic materials and tissue engineered products within the
matrix.
CONCLUSION

1. Jaspreet Kaur Vasir, K. T. (2003). Bioadhesive microspheres as a controlled
drug delivery system. International Journal of Pharmaceutics , 255, 13-32.
2. Satinder Kakar, D. B. (2013). Magnetic microspheres as magical novel drug
delivery system: A review. Journal of Acute Disease , 1-12.
3. Solanki, N. (2018). Microspheres an innovative approach in drug delivery
system. MOJ Bioequivalence & Bioavailability , 5 (1), 56-58
4. HÄFELI, U. (2001). RADIOACTIVE MICROSPHERES FOR MEDICAL
APPLICATIONS. Physics and Chemistry Basis ofBiotechnology , 213-248.
5. Prasad, B. S. (2014). MICROSPHERES AS DRUG DELIVERY SYSTEM – A REVIEW.
Journal of Global Trends in Pharmaceutical Sciences , 5(3), 1961-1972.
6. Prashant Singh, T. g. (2011). Biodegradable Polymeric Microspheres as Drug
Carriers; A Review. Indian Journal of Novel Drug Delivery , 3(2), 70-82.
7. Nirav R. Patel, D. A. (2011). Microsphere as a novel drug delivery.
INTERNATIONAL JOURNAL OF PHARMACY & LIFE SCIENCES , 2 (8), 992-997.
REFERENCES

8.Harsh Bansal, S. P. (2011). MICROSPHERE: METHODS OF PREPRATION AND
APPLICATIONS; A COMPARATIVE STUDY. International Journal of Pharmaceutical
Sciences Review and Research , 10 (1), 69-78.
9.Kadam N R, Suvarna. (2015). MICROSPHERES: A BRIEF REVIEW. Asian Journal of
Biomedical and Pharmaceutical Sciences , 5 (47), 13-19.
10.Wasankar, S. (2012). Drug Delivery to Absorption Window through. Research
Journal of Pharmaceutical technology , 4 (3), 135-142.
11.Kanav Midha, M. N. (2015). MICROSPHERES: A RECENT UPDATE. International
Journal of Recent Scientific Research , 6 (8), 5859-5867.
12.José Ramón., V. S. (2007). Microencapsulation of peptides and proteins.
Biotecnologia Aplicada , 24, 108-116.
13.Ritu Verma, S. V. (2019). Microsphere- A Novel Drug Delivery System. Research
Chronicle in Health Sciences , 5 (1), 5-14.
REFERENCES

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microsphere as drug delivery system

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