This presentation contains all about microencapsulation

1. A Presentation on Microencapsulation
Presented by
Md. Shimul Bhuia
St.ID: 16PHR003
Department of Pharmacy
Bangabandhu Sheikh Mujibur Rahman Science and
Technology University
Gopalganj-8100
Course Title: Pharmaceutical Technology-II
Course Code: PHR361

2. Defination
Microencapsulation is a process by which very tiny droplets or particles
of liquid or solid material are surrounded or coated with a continuous film
of polymeric material.
Microencapsulation may be defined as the process of surrounding or
enveloping one substance within another substance on a very small scale,
yielding capsules ranging from less than one micron to several hundred
microns in size.”
It is mean of applying thin coating to small particle of solid or droplet of
liquid & dispersion.
Microencapsulation is a process by which solids,
Liquids or even gases may be enclosed in microscopic
particles by formation of thin coatings of wall material
around the substances
INTRODUCTION

3. • Particle size: 50-5000 micron.
• 2 phases: a) Core material
b) Coating material
The product obtained by this process is called as micro particles,
microcapsules, microsphere, coated granules, pellets..
Particles having diameter between 3 - 800µm are known as micro
particles or microcapsules or microspheres.
 Particles larger than 1000µm are known as Macroparticles .

4. A well designed controlled drug deliverysystem
- can overcome some of the problems of conventional therapy.
- enhance the therapeutic efficacy of a given drug.

5. To obtain maximum therapeutic efficacy, drug is to be
delivered :
-to the target tissue
-in the optimal amount
-in the right period of time
there by causing little toxicity and minimal side effects.
One such approach is using microspheres as carriers for drugs.
Microspheres are characteristically free flowing powders
consisting of proteins or synthetic polymers
 biodegradable in nature
particle size less than 200 μm.

6. Generally Micro particles consist of two components
a) Core material.
The solid core can be mixture of active constituents, stabilizers,
diluents, excipients and release-rate retardants or accelerators.
b) Coat or wall or shell material
•Compatible, non reactive with core material
•Provide desired coating properties like strength, flexibility,
impermeability, optical properties, non hygroscopicity, tasteless and stable
Fundamental Consideration /Formulation considerations

7. Core Material
The material to be coated. It may be liquid or solid or gas. Liquid core
may be dissolved or dispersed material.
Composition of core material:
Drug or active constituent
Additive like diluents
Stabilizers

8. Coating Material
Inert substance which coats on core with desired thickness.
Composition of coating:
 Inert polymer
 Plasticizer
 Coloring agent
 Resins, waxes and lipids
 Release rate enhancers or retardants
ROLE OF POLYMERS :
 Polymers are substances of high molecular weight made up by repeating
monomer units.
 Polymer molecules may be linear or branched, and separate linear or
branched chains may be joined by crosslinks.
Polymers are used widely in pharmaceutical systems as adjuvants,
coating materials and, a components of controlled and site- specific drug
delivery systems

9. List of coating material
Watersoluble
resin
Water insoluble
resin
Wax & lipid Enteric resin
Gelatin, Ethyl cellulose, Paraffin, Shellac,
Gum arabic, Polyethylene, Carnauba wax, Zein,
PVP,
CMC,
Polymethacrylate,
Cellulose nitrate,
Bees wax,
Stearic acid,
Cellulose acetate
phthalate.
Methyl cellulose, Silicones. Stearyl alcohol.
Arabinogalactan,
Polyvinyl
acrylate,
Polyacrylic acid.

10. REASONS FOR MICROENCAPSULATION
• To protect reactive substances from the environment,
• To convert liquid active components into a dry solid system,
• To separate incompatible components for functional reasons,
• To protect the immediate environment of the microcapsules from the active
components.
• Isolation of core 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.

11. REASONS FOR MICROENCAPSULATION CONT….
• For safe handling of the toxic materials.
• To get targeted release of the drug
• To control release of the active components for delayed (timed) release or
long-acting (sustained) release,
• The problem may be as simple as masking the taste or odor of the core,
• To Increase of bioavailability,
• To produce a targeted drug delivery,
• Protects the GIT from irritant effects of the drug,
• Extension of duration of activity for an equal level of active agent.

12. Microencapsulation
Physical or Physico-
mechanical
Physico-chemical Chemical
1. Air suspension
2. Centrifugal extrusion
3. Pan coating
4. Spray-drying
1. Co-current
2. Counter-current
3. Mixed-flow
5. Vibrational nozzle
1. Ionotropic gelation
2. Coacervation
1. Solvent evaporation
2. Polymerization
1. Interfacial polymer
2. In-situ polymerization
3. Matrix polymer
Classification of microencapsulation techniques

13. Air suspension
• Solid, particulate core materials are
dispersed in a supporting air stream
• The coating material is sprayed on the
air suspended particles
• Within the coating chamber, particles
are suspended on an upward moving air
stream
• The design of the chamber and its
operating parameters effect a
recirculating flow of the particles
through the coating zone portion of the
chamber, where a coating material,
usually a polymer solution, is spray
applied to the moving particles.

14. Air suspension
• During each pass through the coating
zone, the core material receives an
increment of coating material.
• The cyclic process is repeated,
perhaps several hundred times during
processing, depending on:
- the purpose of microencapsulation
- the coating thickness desired
- Until the core material particles are
thoroughly encapsulated.

15. Air suspension
• The supporting air stream also serves
to dry the product while it is being
encapsulated
• Schematics of a fluid-bed coater.
(a) Top spray;
(b) bottom spray;
(c) tangential spray
• Drying rates are directly related to the
volume temperature of the supporting
air stream.

16. Pan coating
Pan coating is a physical method of preparing
microencapsulation and It can only be used for
particles greater than 600 microns in diameter.
Process of microencapsulation by 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 the core particles, and
then is solidified by cooling.
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.

17. 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.

18. Pan coating
The variables that should be controlled in pan coating :
Pan speed : Pan speeds of 10 to 15 rpm are commonly used in nonaqueous film
coating. Speeds that are too slow may cause over wetting resulting in stickiness
and in high speed may cause rough appearance because less time of drying .
Degree of atomization: The higher pressure of nozzles the higher degree of
atomization thus spray droplets will be much smaller. The small droplets will dry
before reaching the capsule beds as a result roughness occurs on capsule.

19. Pan coating
Temperature: High coating chamber temperatures are conducive to
rapid solvent evaporation and consequently to faster coating rate.
Spray pattern: A spray pattern that is too narrow ,localized
over wetting may result .

20. Spray drying & Spray-congealing
Spray drying:
The coating solidification is effected by rapid evaporating of solvent in which coating material is
dissolved.
Microencapsulation by spray-drying is a low-cost commercial process which is mostly used for
the encapsulation of fragrances, oils and flavours.
Steps:
 Core particles are dispersed in a polymer solution and sprayed into a hot chamber.
 The shell material solidifies onto the core particles as the solvent evaporates.
 The microcapsules obtained are of polynuclear or matrix type.

22. Spray-congealing
The coating solidification is effected by thermally congealing a molten coating
material. The removal of solvent is done by evaporation technique.
This technique can be accomplished with spray drying equipment when the
protective coating is applied as a melt.
Steps:
The core material is dispersed in a coating material melt.
Coating solidification(and microencapsulation) is accomplished by spraying the
hot mixture into a cool air stream.
-e.g. microencapsulation of vitamins with digestable waxes for taste masking

24. Spray drying & Spray-congealing
Both process involve
-Dispersing the core material in a liquefied coating substance/spraying
or introducing the coating mixture on to core material.
-Solidification of coating material.
The principal difference between the two method is the means by which coating
solidification is accomplished.
Both process have advantages such as low bulk density product, porous nature
capsules and free flowing particles.

25. Solvent Evaporation
• In the case in which the core material is dispersed in the polymer solution, polymer
shrinks around the core.
• In the case in which core material is dissolved in the coating polymer solution, a matrix -
type microcapsule is formed.
• The core materials may be either
water - soluble or
water - insoluble materials.
• A variety of film - forming polymers can be used as coatings.
• eg. Evaluation of Sucrose Esters as Alternative Surfactants in Microencapsulation of
Proteins by the Solvent Evaporation Method.

26. Solvent Evaporation process…
Core material
Dissolved Or Dispersed
Coating polymer solution
With Agitation
Liquid Manufacturing Vehicle Phase
Heating (If necessary)
Evaporation of Polymer solvent
Microencapsulation

27. SOLVENT EVAPORATIONS

28. SOLVENT EVAPORATIONS

29. SOLVENT EVAPORATIONS

30. Pharmaceutical Application
• To improve the flow properties. e.g. Thiamine, Riboflavin
• To enhance the stability. e.g. Vitamins
• To reduce the volatility of materials. e.g. Peppermint oil, Methyl
• salicylate
• To avoid incompatibilities. e.g. Aspirin and Chloramphenicol
• To mask the unpleasant taste and odour. e.g. Aminophylline, castor oil
• To convert liquids into solids. e.g. Castor oil, Eprazinone,
• To reduce gastric irritation. e.g. Nitrofurantoin, Indomethacin
• Microencapsulation has been employed to provide protection to the core materials
against atmospheric effects, e.g., Vitamin A Palmitate.

31. 42
Polymerization
Arelatively new microencapsulation method utilizes polymerization techniques to
from protective microcapsule coatings in situ.
 The method involve the reaction of monomeric unit located at the interface
existing between a core material substance and continuous phase in which the core
material is disperse.
 The core material supporting phase is usually a liquid or gas, and therefore
polymerization reaction occur at liquid-liquid, liquid-gas, solid-liquid, or solid-gas
interface.
 E.g. In the formation of polyamide (Nylon) polymeric reaction occurring at liquid-
liquid interface existing between aliphatic diamine & dicarboxylic acid halide.

32. Drug
Addition of the alcoholic solution
of the initiator (e.g., AIBN)
8 hrs Reactiontime
Monomer(s) (e.g. acrylamide, methacrylic acid)
+ Cross-linker (e.g. methylenebisacrylamide)
Alcohol
T (reaction) = 60 °C
Nitrogen Atmosphere
Preparation of the
Polymerization Mixture
Initiation of Polymerization
Monodisoerse Latex Formation
by Polymer Precipitation
RECOVERY OF POLYMERIC
MICROPARTICLES
Monodisperse microgels in the
micron or submicron size range.
Precipitation polymerization starts
from a homogeneous monomer
solution in which the synthesized
polymer is insoluble.
The particle size of theresulting
depends on themicrospheres
polymerization
including the
conditions,
monomer/co
monomer composition, the amount
of initiator and the total monomer
concentration.
POLYMERIZATION:

33. Polymerization
1) Interfacial polymer
In Interfacial polymerization, the two reactants in a
polycondensation meet at an interface and react rapidly.
2) In-situ polymerization
In a few microencapsulation processes, the direct
polymerization of a single monomer is carried out on the
particle surface.
e.g. Cellulose fibers are encapsulated in polyethylene while
immersed in dry toluene. Usual deposition rates are about
0.5μm/min. Coating thickness ranges 0.2-75μm.
3) Matrix polymer
In a number of processes, a core material is imbedded in a
polymeric matrix during formation of the particles.
 Prepares microcapsules containing protein solutions by
incorporating the protein in the aqueous diamine phase.
 National Lead Corporation- utilizing polymerization techniques

34. Polymerization Single emulsion method
46

35. Double emulsion method
47

36. Coacervation

39. COACERVATION / PHASE SEPARATION
Polymeric
Membrane
Droplets
Homogeneous
Polymer Solution
Coacervate
Droplets
PHASE
SEPARATION
MEMBRANE
FORMATION
1.Formation of three immiscible phase
2.Deposition of coating
3.Rigidization of coating.

42. PercentageYield
The total amount of microcapsules obtained was weighed and the
percentage yield calculated taking into consideration the weight of the
drug and polymer.
Percentage yield = Amount of microcapsule obtained / Theoretical
Amount×100
Scanning electron microscopy
•Scanning electron photomicrographs of drug loaded ethyl cellulose
microcapsules were taken. A small amount of microcapsules was spread
on gold stub and was placed in the scanning electron microscopy
(SEM) chamber.
•The SEM photomicrographs was taken at the acceleration voltage of
20 KV.
EVALUATION OF MICROCAPSULES

43. Particle size analysis
For size distribution analysis, different sizes in a batch were separated by
sieving by using a set of standard sieves. The amounts retained on
different sieves were weighed .
Encapsulation efficiency
Encapsulation efficiency was calculated using the formula:
Encapsulation efficiency =
Actual Drug Content / Theoretical Drug Content ×100

44. Cefotaxime sodium drug content in the microcapsules was calculated by UV
spectrophotometric method.
The method was validated for linearity, accuracy and precision. A sample of
microcapsules equivalent to 100 mg was dissolved in 25 ml ethanol and the
volume was adjusted upto 100 ml using phosphate buffer of pH 7.4. The
solution was filtered through Whatman filter paper.
Then the filtrate was assayed for drug content by measuring the absorbance
at 254 nm after suitable dilution.
Estimation of Drug Content

45. Drug release was studied by using USP type II dissolution test apparatus (Electrolab TDT
08L) in Phosphate buffer of pH 7.4 (900 ml). The paddle speed at 100 rpm and bath
temperature at 37 ± 0.5°c were maintained through out the experiment.
A sample of microcapsules equivalent to 100 mg of cefotaxime sodiumwas
used in each test. Aliquot equal to 5ml of dissolution medium was withdrawn at specific
time interval and replaced with fresh medium to maintain sink condition. Sample was
filtered through Whatman No. 1 filter paper and after suitable dilution with medium; the
absorbance was determined by UV spectrophotometer (Elico SL159) at 254 nm.
All studies were conducted in triplicate (n=3). The release of drug from marketed sustained
release tablet was also studied to compare with release from microcapsules.
Invitro Drug release Studies

46. APPLICATION OF MICROENCAPSULATION TECHNIQUES

47. Applications of Microcapsules
1. AgriculturalApplications
 Reduce insect populations by disrupting their mating process.
 Protects the pheromone from oxidation and light during storage and release.
2. Catalysis
 Safe handling, easy recovery, reuse and disposal at an acceptable economic
cost.
 Metal species such as palladium (II) acetate and osmium tetroxide have been
encapsulated in polyurea microcapsules and used successfully as recoverable
and reusable catalysts without significant leaching and loss of activity.

48. 3. Food Industry
 Adding ingredients to food products to improve nutritional value
can compromise their taste, colour, texture and aroma.
 Sometimes they slowly degrade and lose their activity, or become
hazardous by oxidation reactions.
 Ingredients can also react with components present in the food
system, which may limit bioavailability.
4. PharmaceuticalApplications
 Potential applications of this drug delivery system are
replacement of therapeutic agents (not taken orally today like
insulin), gene therapy and in use of vaccines for treating AIDS,
tumors, cancer and diabetes.
 The delivery of corrective gene sequences in the form of plasmid
DNA could provide convenient therapy for a number of genetic
diseases such as cystic fibrosis and hemophilia.

49.  Lupin has already launched in the market worlds first Cephalexin
(Ceff-ER) and Cefadroxil (Odoxil OD) antibiotic tablets for
treatment of bacterial infections.
 Aspirin controlled release version ZORprin CR tablets are used
for relieving arthritis symptoms.
 Quinidine gluconate CR tablets are used for treating and
preventing abnormal heart rhythms.
 Niaspan CR tablet is used for improving cholesterol levels and
thus reducing the risk for a heart attack.
 Some of the applications of microencapsulation can be
described in detail as given below:
1. Prolonged release dosage forms.
selectively2.Prepare enteric-coated dosage forms
absorbed in the intestine rather than the stomach.
3. It can be used to mask the taste of bitter drugs.
4. To reduce gastric irritation.
PharmaceuticalApplications

50.  Used to aid in the addition of oily medicines to tableted dosage
 forms. To overcome problems inherent in producing tablets from otherwise tacky
granulations.
 This was accomplished through improved flow properties.
 eg. The non-flowable multicomponent solid mixture of niacin, riboflavin, and
thiamine hydrochloride and iron phosphate may be encapsulated and made directly
into tablets.
 To protect drugs from environmental hazards such as humidity, light, oxygen or
heat. eg. vitamin A and K have been shown to be protected from moisture and
oxygen through microencapsulation.
 The separations of incompatible substances, eg. pharmaceutical eutectics.
 The stability enhancement of incompatible aspirin- chlorpheniramine maleate
mixture was accomplishedby microencapsulating both of them before mixing.
PharmaceuticalApplications

51. Example of Some Microencapsulation

52. Thank you