A Presentation on microsphrere and microencapsulation

1. SUBMITTED BY
Debasish Deka
M. Pharm
Faculty of Pharmaceutical Science
Assam down town University
UNDER THE GUIDANCE OF
Ananta Choudhury
Associate Professor
Faculty of Pharmaceutical Science
Assam down town University

2. CONTENTS
MICROSPHERE
-INTRODUCTION
-ADVANTAGES AND LIMITATION
-TYPES OF MICROSPHERES
-METHOD OF PREPARATION
-EVALUATION OF MICROSPHERES
-APPLICATION OF MICROSPHERES IN PHARMACEUTICAL INDUSTRY
MICROCAPSULATION
-INTRODUCTION
-CHARATERIZATION OF MICROCAPSULATION
-APPLICATION OF MICROCAPSULATION
2

3. 3
Microsphere

4. INTRODUCTION
A well designed controlled drug delivery system can overcome
some of the problems of conventional therapy and enhance the
therapeutic efficacy of a given drug. To obtain maximum
therapeutic efficacy, it becomes necessary to deliver the agent to
the target tissue in the optimal amount in the right period of time
there by causing little toxicity and minimal side effects.
4

5. 5
There are various approaches in delivering a therapeutic
substance to the target site in a sustained controlled release. One
such approach hoi nkiis using microspheres as carriers for drugs.
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 200 µm.
Microspheres used usually are polymers. They are classified
into two types:
1)Natural Polymer
2)Synthetic Polymer

6. Natural
polymers
Synthetic
Polymers
carbohydrates
proteins
chemically modified
Carbohydrates
Biodegradable
polymer
Non Biodegradable
polymerAgarose
Gelatin
Poly starch
Glycolides
Epoxypolymer
Polymer
6

7. ADVANTAGES
1.Microspheres provide constant and prolonged therapeutic
effect.
2.Reduces the dosing frequency and thereby improve the patient
compliance.
3.They could be injected into the body due to the spherical
shape and smaller size.
4.Provide constant and prolonged therapeutic effect.
5.Provide constant drug concentration in blood there by
increasing patent compliance.
6.Convert liquid to solid form & to mask the bitter taste.
7.Protects the GIT from irritant effects of the drug.
.
5

8. 8
LIMITATION
Some of the disadvantages were found to be as follows
1.The modified release from the formulations.
2.Differences in the release rate from one dose to another.
3.Dosage forms of this kind should not be crushed.
4.The costs of the materials and processing of the controlled
release preparation, are substantially higher than those of
standard formulations.
5.Process conditions like change in temperature, pH, solvent
addition, and evaporation/agitation may influence the stability
of core particles to be encapsulated.

9. MICROSPHERES
Bioadhesive
Magnetic
Floating
Radioactive
Polymeric
TYPES OF MICROSPHERES:
9

10. 1.Bioadhesive microspheres:
Adhesion can be defined as sticking of drug to the membrane
by using the sticking property of the water soluble polymers.
Adhesion of drug delivery device to the mucosal membrane
such as buccal, ocular, rectal, nasal etc. can be termed as bio
adhesion. These kinds of microspheres exhibit a prolonged
residence time at the site of application and causes intimate
contact with the absorption site and produces better
therapeutic action.
10

11. 11
2. Magnetic microspheres:
This kind of delivery system is very much important which
localises the drug to the disease site. In this 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 types are
a. Therapeutic magnetic microspheres used to deliver
chemotherapeutic agent to liver tumour. Drugs like proteins and
peptides can also be targeted through this system.
b. Diagnostic microspheres, used for imaging liver metastases.

12. 12
4. Radioactive microspheres:
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
tissues.
3. Floating microspheres:
It reduces chances of dose dumping.
It produces prolonged therapeutic effect and therefore reduces
dosing frequencies. Drug (ketoprofen) is given in the form of
floating microspheres.

13. 13
5. Polymeric microspheres:
The different types of polymeric microspheres can be
classified as follows and they are
A) Biodegradable polymeric microspheres
B) Synthetic polymeric microspheres.

14. METHOD OF PREPARATION:
1. Spray Drying
2. Solvent Evaporation
3. Single emulsion technique
4. Double emulsion technique
5. Spray drying and spray congealing
6. Solvent extraction
Spray Drying
14

15. 15
Dissolved in a suitable volatile organic solvent such as
dichloromethane, Acetone, etc.
Then dispersed in the polymer solution under high-speed
homogenization
Then atomized in a stream of hot air.
Formation of the small droplets
solvent evaporate
Formation of the microspheres in a size range 1-100μm
Micro particles are separated from the hot air by means of
the cyclone separator while the trace of solvent is removed
by vacuum drying

16. 16
This process is carried out in a liquid manufacturing vehicle
phase. 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.
Solvent Evaporation

17. 17
If the core material is dissolved in the coating polymer
solution, matrix – type microcapsules are formed .The core
materials may be either water soluble or water in soluble
materials. Solvent evaporation involves the formation of an
emulsion between polymer solution and an immiscible
continuous phase whether aqueous (o/w) or non-aqueous.

18. 18
Single emulsion technique

19. 19
Double emulsion technique
Double emulsion method of microspheres preparation involves
the formation of the multiple emulsions or the double emulsion
of type w/o/w and is best suited to water soluble drugs,
peptides, proteins and the vaccines. This method can be used
with both the natural as well as synthetic polymers.
Spray drying and spray congealing
These methods are based on drying of the mist of the polymer
and drug in the air. Depending on the removal of the solvent or
cooling of the solution, the two processes are named spray
drying and spray congealing.

20. 20

21. One of the major merits of the process is feasibility of process
under aseptic conditions. Spray drying process is used to
encapsulate various penicillins. Thiamine Mononitrate and sulpha
ethylthiadizole are encapsulated in a composition of mono- and
diglycerides of palmitic acid and stearic acid using spray
congealing. Very rapid solvent evaporation, however leads to the
formation of porous microparticles.
21

22. 22
Solvent extraction
Solvent evaporation method is used for manufacturing of
microparticles, involves removal of the organic phase by
extraction of the or non aqueous solvent. This method
involves water miscible organic solvents as isopropanol.
Organic phase can be removed by extraction with water. This
process decreases the hardening time for the microspheres.

23. EVALUATION OF MICROSPHERES:
1. Particle size and shape
The most widely used procedures to visualize microparticles are
conventional light microscopy (LM) and scanning electron
microscopy (SEM).
2. Electron spectroscopy for chemical analysis:
The surface chemistry of the microspheres can be determined by
using the electron spectroscopy for chemical analysis (ESCA).
3. Density determination:
The density of the microspheres can be measured by using a multi
volume pycnometer.
4. Angle of contact:
The angle of contact is measured to determine the wetting property of
a micro particulate carrier.
23

24. 6. Drug entrapment efficiency:
Drug entrapment efficiency can be calculated using following
equation,
% Entrapment = Actual content/Theoretical content x 100.
5. In vitro methods:
Release studies for different type of microspheres are carried out
by using different suitable dissolution media, mostly by rotating
paddle apparatus (USP / BP).
APPLICATION OF MICROSPHERES IN
PHARMACEUTICAL INDUSTRY:
24
1.Buccal Drug Delivery: Polymer is an excellent polymer to be
used for buccal delivery because it has muco / bioadhesive
properties and can act as an absorption enhancer. Chitosan,
Sodium alginate.

25. 25
2.Intratumoral and Local Drug Delivery: In order to
deliver paclitaxel at the tumor site in therapeutically relevant
concentration, polymer films are fabricated. Mixture of drug
has promising potential for use in controlled delivery in the
oral cavity e.g. Gelatin, PLGA, Chitosan.
3.Gastrointestinal Drug Delivery: Polymer granules having
internal cavities prepared by de acidification when added to
acidic and neutral media are found buoyant and provided a
controlled release of the drug e.g. Eudragit, Ethyl cellulose +
Carbopol BSA, Gelatin.
4.Transdermal Drug Delivery: Polymer has good film-
forming properties. The drug release from the devices is
affected by the membrane thickness and cross-linking of the
film. e.g. Chitosan, Alginate, PLGA.

26. Microencapsulation
26

27. Microencapsulation is a process by which solids, liquids
or even gases may be enclosed in microscopic particles
formation of thin coatings of wall material around the
substances.
The process had its origin in the late 1930s as a cleaner
substitute for carbon paper and carbon ribbons as sought
by the business machines industry. The ultimate
development in the 1950s of reproduction paper and
ribbons that contained dyes in tiny gelatin capsules
released on impact by a typewriter key or the pressure of a
pen or pencil was the stimulus for the development of a
host of microencapsulated materials, including drugs
INTRODUCTION
27

28. 28
Microencapsulation provides the means of converting
liquids to solids, of altering colloidal and surface
properties, of providing environmental protection and
of controlling the release characteristics or availability
of coated materials.
Fig. 1: Microencapsulation process

29. -This technique can be used for converting liquid drugs in
a free flowing powder.
- The drugs, which are sensitive to oxygen, moisture or
light, can be stabilized by microencapsulation.
- Vaporization of many volatile drugs e.g. methyl
salicylate and peppermint oil can be prevented by
microencapsulation.
- Many drugs have been microencapsulated to reduce
toxicity and GI irritation including ferrous sulphate and
KCl..
- Toxic chemicals such as insecticides may be
microencapsulated to reduce the possibility of
sensitization of factorial person.
- Bakan and Anderson reported that microencapsulated
vitamin A palmitate had enhanced stability.
29

30. The reasons for microencapsulation
The reasons for microencapsulation are countless. In
some cases, the core must be isolated from its
surroundings, as in isolating vitamins from the
deteriorating effects of oxygen, retarding evaporation of
a volatile core, improving the handling properties of a
sticky material, or isolating a reactive core from
chemical attack. In other cases, the objective is not to
isolate the core completely but to control the rate at
which it leaves the microcapsule, as in the controlled
release of drugs or pesticides. The problem may be as
simple as masking the taste or odor of the core.
Microsphere & microcapsule
30

31. 31
COATING MATERIAL PROPERTIES
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.

32. 32
Examples of coating materials:
1.Water soluble resins – Gelatin, Gum Arabic, Starch,
Polyvinyl pyrrolidone,Carboxy methyl cellulose, Hydroxy ethyl
cellulose, Methyl cellulose, Polyvinyl alcohol , Arabinogalactan,
, Polyacrylic acid.
2.Water insoluble resins – Ethylcellulose, Polyethylene,
Polymethacrylate, Polyamide(Nylon), Poly(Ethylene- Vinyl
acetate), Cellulose nitrate, Silicones.
3.Waxes and lipids – Paraffin, Carnauba, Spermaceti, Beeswax,
Stearic acid, Stearyl alcohol, Glyceryl stearates .
4. Enteric resins – Shellac, Cellulose acetate phthalate.

33. 33
CHARACTERIZATION OF MICROCAPSULE
-Angle of contact
The angle of contact is measured to determine the wetting
property of a micro particulate carrier
-Particle size
The microparticle size can be determined by laser
diffractometry using a Malvern Mastersizer X
-Dissolution apparatus
Standard USP or BP dissolution apparatus have been used to
study in vitro release profiles using both rotating elements
(paddle and basket)
-Sieve analysis
Separation of the microspheres into various size fractions can
be determined by using a mechanical sieve shaker

34. APPLICATION
34
-Quality and safety in food, agricultural & environmental
sectors.
- Beverage production

35. 35
- Protection of liquid crystals.
- Soil inoculation.
- To mask the bitter taste of drugs like Paracetamol,
Nitrofurantoin etc.

36. THANK YOU
36