This document provides information about microspheres including their definition, advantages, types, polymers used, preparation methods, and applications. Microspheres are solid, approximately spherical particles ranging from 1 to 1000 μm that are made of polymeric, waxy, or other protective materials and used as drug carrier matrices. They can be prepared using various methods including air suspension, coacervation, spray drying, solvent evaporation, and polymerization. Microspheres find applications in targeted drug delivery, sustained release formulations, and mucoadhesive drug delivery systems. Their properties and drug release kinetics are evaluated through studies such as drug entrapment efficiency, particle size analysis, in vitro drug release, and mathematical modeling of release profiles.

1. Formulation And Invitro Evaluation Of
Microspheres
Presented By
K. Tejaswi
Vignan Institute of Pharmaceutical Sciences
Deshmukhi, Nalgonda.
(note:ppt compatible with office2013 and 2007)
1

2. CONTENTS :
• Introduction
• Methodology
• Evaluation studies
• Bibliography
2

3. DEFINITION :
• Microspheres can be defined as solid, approximately spherical particles
raging in size from 1 to 1000 µm.
• Made up of polymeric, waxy, or other protective materials such as starches,
gums, proteins, fats and used as drug carrier matrices for drug delivery.
• Microspheres : micrometric matrix systems.
• Natural polymer can also be used :
Albumin
gelatin 3

4. 4
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’.

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

6. POLYMER USED FOR MICROSPHERES
PREPARATIONS :
BIODEGRADABLE
• Lactides & Glycolides and their
copolymers
• Polyanhydrides
• Polycynoacrylates
NON-BIODEGRADABLE
• Poly methyl methacrylate
• Acrolein
• Epoxy Polymer
• Glycidyl methacrylate
6

7. 7

8. APPLICATIONS :
• Taste and odor masking
• Conversion of oils and other liquids to solids for ease of handling
• Protection of drugs against the environment and vice versa
• Delay of volatilization
• Separation of incompatible materials
• Improvement of flow of powders
• Safe handling of toxic substances
• Aid in dispersion of water-insoluble substances in aqueous media, and
• Production of sustained-release, controlled-release, and targeted
medications
• Reduced dose dumping potential compared to large implantable devices
8

9. MUCOADHESION / BIOADHESION :
• Mucoadhesive drug delivery system are the systems which utilizes the
property of bio adhesion of certain polymers which become adhesive on
hydration and can be used for targeting a drug to a particular region of the
body for extended periods of time.
• The term “mucoadhesion” was coined for the adhesion of the polymers with
the surface of the mucosal layer. Bio adhesions are a phenomenon in which
two materials at least one of which is biological and are held together by
means of interfacial forces.
9

10. BIOADHESION – CLASSIFICATION :
TYPE – 1 :
• Adhesion between two biological phases, for example, platelet aggregation and
wound healing.
TYPE – 2 :
• Adhesion of a biological phase to an artificial substrate, for example, cell adhesion
to culture dishes and bio film formation on prosthetic devices and inserts.
TYPE – 3 :
• Adhesion of an artificial material to a biological substrate, for example, adhesion of
synthetic hydrogels to soft tissues and adhesion of sealants to dental enamel.
10

11. ADVANTAGES OF MUCOADHESIVES
OVER CONVENTIONAL DOSAGE FORMS :
• Readily localized in the region applied to improve and enhance the
bioavailability of drugs. E.g. testosterone & its esters, vasopressin, dopamine,
insulin and gentamycin etc.
• Facilitate intimate contact of the formulation with underlying absorption
surface. This allows modification of tissue permeability for absorption of
macromolecules. e.g. peptides and proteins.
• Prolong residence time of the dosage form at the site of application and
absorption to permit once or twice a day dosing. 11

12. MECHANISM OF MUCOADHESION :
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. A general mechanism of
mucoadhesion drug Delivery system is
show in figure.
12

13. THEORIES OF MUCOADHESION :
• Electronic theory
• Wetting Theory
• Adsorption Theory
• Diffusion theory
• Mechanical Theory
• Cohesive Theory
13

14. Electronic theory:
Involves the formation of an electric double layer at the mucoadhesive interface by the transfer of
electrons between the mucoadhesive polymer and the mucin glycoprotein network. For example:
interaction between positively charged polymers chitosan and negatively charged mucosal surface
which becomes adhesive on hydration and provides an intimate contact between a dosage form and
absorbing tissue.
Wetting theory:
States that if the contact angle of liquids on the substrate surface is lower, then there is a greater
affinity for the liquid to the substrate surface. If two such substrate surfaces are brought in contact
with each other in the presence of the liquid, the liquid may act as an adhesive amongst the substrate
surfaces.
Adsorption theory:
According to this theory, after an initial contact between two surfaces, the material adheres because of
surface force acting between the atoms in two surfaces. Two types of chemical bonds resulting from
these forces can be distinguished as primary chemical bonds of covalent nature and secondary
chemical bonds having many different forces of attraction likes electrostatic forces, vander walls
forces, hydrogen and hydrophobic bonds.
14

15. Diffusion theory:
According to this theory, the polymer chains and the mucus mix to a sufficient depth to create a
semi permanent adhesive bond. The exact depth to which the polymer chain penetrates the
mucus depends on the diffusion coefficient and the time of contact. The diffusion coefficient in
terms depends on the value of molecular weight between cross linking and decreases
significantly as the cross linking density increases.
Mechanical theory:
Explains the diffusion of the liquid adhesives into the micro-cracks and irregularities present on
the substrate surface thereby forming an interlocked structure which gives rise to adhesion.
Cohesive theory:
Proposes that the phenomena of bio adhesion are mainly due to the intermolecular interactions
amongst like-molecules. Based on the above theories, the process of bio adhesion can be
broadly classified into two categories,
1. chemical: electronic and adsorption theories
2. physical: wetting, diffusion and cohesive theory.
The process of adhesion may be divided into two stages. During the first stage (also known as
contact stage), wetting of mucoadhesive polymer and mucous membrane occurs followed by
the consolidation stage, where the physicochemical interactions take place.
15

16. METHODS OF PREPARATION OF
MUCOADHESIVE MICROSPHERES:
• Air suspension
• Coacervation
• Spray drying
• Solvent evaporation
• Polymerization
• Wet inversion technique
• Hot melt microencapsulation
16
• Solvent removal
• Preparation of microspheres by
thermal cross-linking
• Preparation of microspheres by
glutaraldehyde cross linking
• Preparation of microspheres by Tri
polyphosphate
• Iontropic gelation technique

17. AIR SUSPENSION :
This process consists of the
dispersing of solid particles of core
materials in a supporting air stream
and the spray coating of the air
suspended particles.
17

18. COACERVATION :
18
Aq./organic solution of polymer
Drug dispersed or dissolved in the polymer solution
Polymer rich globules
Microspheres in aqu./organic phase
MICROSPHERES
Phase sepration by salt addition, non solvent addition
add.
Incompatible polymer,etc
Hardening
separation/drying

19. 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
19

20. SOLVENT EVAPORATION :
20

21. POLYMERIZATION :
A)Normal Polymerization
Normal Polymerization is done by bulk, suspension, precipitation, emulsion
and polymerization process.
1. Bulk polymerization:
21
Monomer
+ Bioactive
material
+
Initiator
Heated to initiate polymerization
Initiator accelerate rate of reaction
Polymer
(block)
Moulded/fragmented Microspheres

22. B)Suspension polymerization
Monomer Bioactive material Initiator
Dispersion in water and stebilizer
Droplet
Vigorous Aggitation Polymerization by Heat
Hardened microspheres
Separation & Drying
MICROSP HERES
22

23. 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 23

24. HOT MELT MICROENCAPSULATION :
• The polymer is first melted and then mixed with solid particles of the drug that have been
sieved to less than 50 μm.
• 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 stabilized, it is cooled until the polymer particles solidify. The resulting
microspheres are washed by decantation with petroleum ether.
• The primary objective for developing this method is to develop a microencapsulation process
suitable for the water labile polymers, e.g. poly anhydrides.
• 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
moderate temperature to which the drug is exposed.
24

25. 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
25

26. WET INVERSION TECHNIQUE :
• Chitosan solution in acetic acid was dropped in to an aqueous solution of
counter ion sodium tripolyposphate through a nozzle.
• Microspheres formed were allowed to stand for 1 hr and cross linked with
5% ethylene glycol diglysidyl ether.
• Microspheres were then washed and freeze dried. Changing the pH of the
coagulation medium could modify the pore structure of CS microspheres.
26

27. IONTROPIC GELATION TECHNIQUE :
• In the ionotropic gelation method polysaccharides (alginate, gellan and p
ectin) are dissolved in water or in weak acidic medium (chitosan).
• These solutions are then added dropwise under constant stirring to the
solutions containing other counter ions.
• Due to the complexation between oppositely charged species,
polysaccharides
undergo ionic gelation and precipitate to form spherical particles.The
beads are removed by filtration, washed with distilled water and dried. 27

28. ORIFICEIONIC GELATION METHOD :
Sodium Alginate mucoadhesive polymer
Disperse in purified water
Homogenous polymer mixture
Addition of API
Mix thoroughly to form viscous dispersion
Add to CaCl2 solution with continuous stirring
Rigid spherical Microspheres
28

29. PREPARATION OF MICROSPHERES BY
THERMAL CROSS-LINKING :
• Citric acid, as a cross-linking agent was added to 30 mL of an aqueous acetic acid
solution of chitosan (2.5% w/v) maintaining a constant molar ratio between chitosan
and citric acid (6.90 × 10−3 mol chitosan : 1 mol citric acid).
• The chitosan cross-linker solution was cooled to 0°C and then added to 25 mL of
corn oil previously maintained at 0°C, with stirring for 2 minutes.
• This emulsion was then added to 175 mL of corn oil maintained at 120°C, and cross-
linking was performed in a glass beaker under vigorous stirring (1000 rpm) for 40
minutes.
• The microspheres obtained were filtered and then washed with diethyl ether, dried,
and sieved.
29

30. PREPARATION OF MICROSPHERES BY
GLUTARALDEHYDE CROSS LINKING :
• A 2.5% (w/v) chitosan solution in aqueous acetic acid was prepared. This dispersed phase
was added to continuous phase (125 mL) consisting of light liquid paraffin and heavy liquid
paraffin in the ratio of 1:1 containing 0.5% (w/v) Span 85 to form a water in oil (w / o)
emulsion.
• Stirring was continued at 2000 rpm using a 3- blade propeller stirrer. A drop-by-drop solution
of a measured quantity (2.5 mL each) of aqueous glutaraldehyde (25% v/v) was added at 15,
30, 45, and 60 minutes.
• Stirring was continued for 2.5 hours and separated by filtration under vacuum and washed,
first with petroleum ether (60 °C- 80 °C) and then with distilled water to remove the adhered
liquid paraffin and glutaraldehyde, respectively.
• The microspheres were then finally dried in vacuum desiccators.
30

31. PREPARATION OF MICROSPHERES BY
TRI POLYPHOSPHATE :
• Chitosan solution of 2.5% w/v concentration was prepared.
• Microspheres were formed by dropping the bubble-free dispersion of
chitosan through a disposable syringe (10 mL) onto a gently agitated
(magnetic stirrer) 5% or 10% w/v Tri polyphosphate solution.
• Chitosan microspheres were separated after 2 hours by filtration and rinsed
with distilled water, and then they were air dried.
31

32. APPLICATIONS :
• Vaccine delivery for treatment of diseases like hepatitis, influenza, pertusis, ricin
toxoid, diphtheria, birth control.
• Passive targeting of leaky tumour vessels, active targeting of tumour cells, antigens,
by intra arterial / intravenous application.
• Chemoembolisation
• Imaging
• Topical porus microspheres
• Surface modified microspheres
32

33. EVALUATION PARAMETERS :
• Preformulation studies
Spectroscopic studies
Linear regression analysis
Compatibility studies
• Characterization of
Microspheres
Percentage yield
Drug entrapment efficiency
Particle size analysis
Swelling study
Mucoadhesive property
Invitro drug release study
33
• Drug release kinetics
Zero order
First order
Matrix (Higuchi Matrix)
Peppas korsmeyer
equation

34. BIBLIOGRAPHY :
• Shiva Kumar Yellanki, Jeet Singh , Jawad Ali Syed , Rajkamal Bigala , Sharada Goranti , Naveen
Kumar nerella Design and Characterization of Amoxicillin trihydrate Mucoadhesive Microspheres for
Prolonged Gastric retention IJPSDR April-June, 2010, Vol 2, Issue 2 (112-114)
• Wattamwar Mayur M, Ratnaparkhi Mukesh P, Kutmalge M.D , Jadhav A. N Formulation and in vitro
evaluation of mucoadhesive microspheres of pioglitazone hydrochloride Asian Pac. J. Health Sci.,
2014; 1(3): 177-192
• Pavan Kumar Perumandla , Sree Priya Formulation And In Vitro Evaluation Of Floating Microspheres
Of Dextromethorphan Hydrobromide Int J Pharm Pharm Sci, Vol 6, Issue 4, 206-210
• Kutmalge M. D., Ratnaparkhi M. P., Jadhav A. N., Wattamwar M. M., Bangar J. V. and S. P. Chaudhari
Formulation and in-vitro evaluation of lornoxicam floating microsphere Der Pharmacia Lettre, 2014, 6
(4):169-183
• V. Ganesan , V.S.V.S.P. Krishna Kanth Preparation and In-vitro Evaluation of Microballoon Drug
34

35. 35
Any Query