Novel drug delivery system

1. Mr’s Vidhya V. Mali
Asst. Prof. R P College of Pharmacy
Osmanabad

2. Contents
 Introduction
 Definition
 Advantages
 Disadvantages
 Reasons for Microencapsulation
 Formulation Consideration
 Release Mechanisms
 Microencapsulation Techniques
 Applications of Microencapsulation

3. Introduction
 Microencapsulation is a process in which small particles or droplets
(core material) is surrounded by a shell or coat (coating material) to
give small capsules.
Their diameters generally range from a few microns to a few
millimetres . (1µm-1000µm)
Solids, liquids or gasses may be enclosed by thin coating of wall or
polymeric material.
Increase safety and efficacy of drug.
Maintain the desired concentration at the site of action.
Process of surrounding or enveloping one substance within another
substance on a very small scale.

4. Definition
 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.
 The product obtained by this process
is called as micro particles, microcapsules,
microspheres, coated granules and pellets .
 Particles having diameter between 3 - 800µm are known as micro
particles or microcapsules or microspheres.
 Particles larger than 1000µm are known as Macro particles .

5. Microcapsules and Microspheres
 Microcapsules are small particles that contain an active agent (core
material) surrounded by a shell or coating.
Their diameters generally range from a few microns to a few
milimetres.

6. Microcapsules and Microspheres
Microcapsules can have many different types and structures:
 a) Simple droplets of liquid core material surrounded by a spherical
shell (Microcapsules)
 b) Irregularly-shaped particles containing small particles of solid
core material dispersed in a continuous polymer shell matrix
)Microspheres).

7. Advantages
 To Improve bioavailability and reduce untoward effects.
 To extend or alter the drug release.
 To improve the safety and patient’s compliance.
 To produce a targeted drug delivery.
 To reduce the reactivity of the core in relation to the outside
environment.
 To decrease evaporation rate of the core material.
 To convert liquid to solid form & To mask the core taste.
 Microspheres are used for targeting of anticancer drugs to the
Tumors

8. Disadvantages
 It is an expensive process.
 Difficult to achieve continuous and uniform film.
 Shelf life of hygroscopic drugs is reduced.
 Polymer may produce toxic effect.
 Require skills.

9. Reasons for
Microencapsulation

10. Formulation Consideration
Generally Micro particles consist of two components
a) Core material
b) Coat or wall or shell material.
Core Material Coating Material Vehicle
Aqueous
Non-
aqueous
Polymers
Waxes
Resins
Proteins
Polysaccharide
s
Solid
Liquid
Microencapsulation

11. Formulation Consideration
a) Core material:
The material to be coated. It may be liquid or solid or gas.
Composition : 1. Drug or active constituents.
2. Additive like diluents.
3. Stabilizers.
b) Coat or wall or shell material:
Inert substance which coated on core with desired thickness.
Composition : 1. Inert Polymer.
2. Plasticizers.
3. Coloring agents.
4. Resins, waxes and lipids.
5. Release rate enhancers or retardants.

12. Formulation Consideration
 Role of Polymers:
Polymers are used widely in pharmaceutical system as: adjuvant,
coating material and a component of controlled and site specific drug
delivery system.
 Coating Material Properties:
◦ Stabilization of core material.
◦ Inert toward active ingredient.
◦ Controlled release under specific condition.
◦ Film-forming, pliable, tasteless and stable.
◦ Non-hygroscopic, no high viscosity, economic.
◦ Soluble in aqueous media or solvent or melting.
◦ The coating can be flexible, brittle, hard, thin etc
Core
Coating

13. Release Mechanisms

14. Microencapsulation Techniques

15. Air suspension Techniques
Air suspension technique is also called Wruster Process and Fluidized
bed coating.
Principle :
1. The Wrurster process consists of the dispersing of solid particulate
core materials in a supporting air stream and the spray-coating of
the air suspended particles.
2. Within the coating chamber, particles are suspended on an upward
moving air stream as indicated in the drawing.
3. The design of the chamber and its operating parameters provide 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.

16. Air suspension Techniques
4. During each pass through the coating zone, the core material receives
an increment of coating material.
5. The cyclic process is repeated several times during processing,
depending on the purpose of microencapsulation, the coating thickness
desired.
6. The air stream also serves to dry the product while it is being
encapsulated.

17. Air suspension TechniquesWorking :
Fine solid core materials are suspended
by a vertical current of air
Evaporation of the solvent
The encapsulating material is
deposited onto the core material
Achieved the desired film thickness
The encapsulated product is dried by
passing the stream air

18. Air suspension TechniquesWorking :

19. Air suspension TechniquesWorking :
Disadvantage:
Agglomeration of the particles to some larger size is normally
achieved.

20. Air suspension Techniques
 Variables for Efficient, Effective Encapsulation by Air
Suspension Techniques:
1. Density, surface area , melting point, solubility, friability, volatility,
crystallinity and flow ability of core material.
2. Concentration of coating material.
3. Rate of coating material application.
4. Volume of air for fluidization of core material.
5. Amount of coating material.
6. Inlet and outlet operating temperature.

21. Pan Coating
Principle:
 Pan coating process is and widely used in
pharmaceutical industry.
 Oldest method for coating.
 Particles are tumbled in a pan or a device while the
coating material is applied slowly.
 Solid particles greater than 600µ are effectively coated.
 It is used for preparation of controlled release beads.
 Coating can be applied as solution by atomized spray.

22. Pan Coating
Working:
 Core material is tumbled in a pan and Coating material is
applied slowly .
 Coating is applied as a solution or as an atomized spray.
 Warm air is passed over a coated material for removing the
coating solvent.
 In some cases solvent removal can be accomplished by
drying oven.

23. Pan Coating Working :
Solid particles are mixed with a dry
coating material
Temperature is raised
The coating material melts and
encloses the core particles
Achieved the desired film thickness
Then is solidified by cooling

24. Spray drying
 Coating is followed by rapid evaporation of solvent in which coating
material is dissolved.
 Removal of solvent is done by Absorption, Evaporation and Extraction
technique.
Principle: Dispersing the core material into coating substance and
spraying for solidification.
 Formation of microcapsules is followed by following two different
methods
 Spray drying
 Spray congealing(cooling/chilling)

25. Spray drying
 Rapid evaporation of solvent in which the
coating material is dissolved.
Steps:
1. Core particles are dispersed in a polymer
solution and sprayed into a hot chamber.
2. The shell material solidifies onto the core
particles as the solvent evaporates.
3. The microcapsules obtained are of
polynuclear or matrix type.

26. Spray drying
Equipment components of a standard spray dryer include:
1. An air heater
2. Atomizer
3. Main spray chamber
4. Blower or fan
5. Cyclone
6. Product collector
Advantages:
 Low cost commercial process
 Mostly used for encapsulation of fragrances , oils and flavors

27. Spray congealing(cooling/chilling)
 Core material is dispersed in a coating material melt rather than
coating solution.
 Coating solidification (and microencapsulation ) is accomplished by
spraying the hot mixture into a cool air stream.
Steps:
1. Preparation of dispersion or emulsion.
2. Homogenization of the dispersion.
3. Atomization of mass into a dry cylinder.

28. Spray congealing(cooling/chilling)
Spray drying: Spray = Aqueous solution/ Hot air
Spray Congealing: Spray= Hot melt/ Cold air

29. Spray congealing(cooling/chilling)
Advantages:
1. Least expensive encapsulation technology.
2. Used for encapsulation of organic and inorganic salts, textural
ingredients, enzymes, flavors and other functional ingredients.
3. It improves heat stability, delay release in wet environment and
convert liquid into free flowing powders.
Coating material used in spray drying:
 Gum acacia, maltodextrins, hydrophobically modified starch and
mixtures.
 Other polysaccharides like alginate, carboxy methyl cellulose and
guar gum.
 Proteins : Whey proteins, soy proteins, sodium caseinate etc.

30. Coacervation
 Coacervation microencapsulation is the phase separation of one or
more hydrocolloids from the initial solution and subsequent
deposition of the newly formed coacervate around the active
ingredient.
 Typically used for encapsulate flavor oil, fish oils, nutrients,
vitamins, preservatives and enzymes.
There are two methods of coacervation microencapsulation.
1. Simple coacervation
2. Complex coacervation
The mechanism for both processes is identical except for the way in
which the phase separation is carried out.

31. Simple Coacervation

32. Complex Coacervation

33. Ionotropic Gelation Technique
 In this method, Polysaccharides(Sod. Alginate, gellan gum, pectin)
are dissolved in water or in weak acidic medium (chitosan).
 This solution is added drop wise under a constant stirring to the
solution containing other counter/multivalent ions.
 Due to complexation between
oppositely charged ions polysaccharide
undergoes ionic gelation and precipitate
to form spherical particles.
 Beads are removed by filtration,
 washed with distilled water and dried.

34. Ionotropic Gelation Technique
 The counterions used in ionotropic gelation method :
 Low molecular weight counter ions-
(e.g. CaCl2, BaCl2, MgCl2, CuCl2, ZnCl2)
 High molecular weight counter ions-
(Octyl sulphate, Lauryl sulphate, hexadecyl sulphate)

35. Solvent Evaporation (Chemical
process)
 In this case the core material is
dissolved in a coating polymer
solution.
 Polymer shrinks around core material.
 Evaporation of solvent.
 A matrix type microcapsules are
formed.
 Core material may be water-soluble or
water-insoluble.

36. Solvent Evaporation (Chemical
process)
 Step 1: Formation of
emulsion/dispersion
(Drug and organic polymer
phase).
 Step 2: Emulsification of
polymer phase into aqueous
phase (Containing suitable
stabilizer thus forming o/w emulsion).
 Step 3: Removal of the organic
solvent from the dispersed
phase by extraction or
evaporation
(polymer precipitation to form

37. Single Emulsion Method
 The natural polymers (proteins and carbohydrates) are
dissolved/dispersed In aqueous medium followed by non-aqueous
medium (oil).
 In second step crosslinking of dispersed globules is carried out either by
means of heat or by using chemical cross linkers.
 Chemical crosslinking agents: gluteraldehyde, formaldehyde, terepthalate
chloride, diacidchloride etc.

38. Double Emulsion
Method This type involves formation of the multiple emulsions or the double emulsion
of type o/w/o.
 Suitable for water-soluble drugs, peptides, proteins and the vaccines.
 The aqueous protein solution is dispersed in organic coating polymer solution
which encapsulate protein (primary emulsion).
 The primary emulsion is then subjected to homogenization before addition to
aqueous solution of PVA.
 This will result in formation of double emulsion.
 Removal or evaporation of solvent by maintaining at reduced pressure or by
stirring continuously.

39. Polymerization
 It is relatively new microencapsulation process utilizes polymerization
techniques to form protective microcapsule coating in-situ.
 This method involves reaction of monomeric unit located at the interface
between core material and continuous phase in which core material is
dispersed.
 The core material supporting phase is liquid or gas and therefore
polymerization reaction occurs 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 and dicarboxylic acid halide.

40. Polymerization
 There are three different
methods of polymerization:
1. Interfacial polymer
2. In-situ polymerization
3. Matrix polymer

41. Polymerization

42. Polymerization

43. Multiorific-centrifugal Process
 Developed by- Southwest Research
Institute (SWRI)
 Encapsulate solid particle and liquid
droplets
 Mechanical process that utilizes
centrifugal forces to hurl a core
particle through an enveloping
microencapsulation membrane there
by effecting mechanical
microencapsulation.

44. Multiorific-centrifugal Process
 Production rate is about 50 to 75 pounds per hour
Processing variables include;
 The rationale speed of the cylinder
 The flow rate of the core
 The flow rate of coating material
 Concentration, viscosity and surface tension of core material.
Advantages:
 Capable for microencapsulating solid and liquid of varied size
ranges with diverse coating material.
 Production rate is higher.

45. Vibrational Nozzle
 The fluid stream of liquid core and
coating material is pumped through
concentric tubes by a laminar flow
through a nozzle and forms droplets
under the influence of vibration.
 The vibration has to be done in
resonance of Rayleigh stability and
leads to form very uniform droplets.
 Solidification done by gelation process
 Particle between 100-5000 µm
encapsulated.

47. Applications of Microencapsulation
 Agricultural application
 Catalysis
 Food industry
 Pharmaceutical application
 Other applications

48. Applications of
Microencapsulation
 Prolonged release dosage forms.
 Prepare enteric coated dosage forms.
 Mask the taste of bitter drugs.
 To reduce gastric irritation.
 Aid in the addition of oily medicine into the tablet dosage forms.
 To overcome problems inherent in producing tablets from
otherwise tacky granulations.
 To protect drugs from environmental hazards such as humidity,
light, oxygen or heat.
e.g. - Vitamin A and K have been shown to be protected from
moisture and oxygen through microencapsulation.
 The separation of incompatible substances e.g. pharmaceutical
eutectics.

49. Applications of
Microencapsulation
 To improve 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 liquid into solid. e.g. Castor oil, Eprazinone.
 To reduce gastric irritation. e.g. Nitrofuranation,
Indomethacin.
 To Protect core material from atmosphere. e.g. Vitamin A
palmitate.

50. Question’s
1. Define microencapsulation. List out the advantages and
disadvantages of microencapsulation.
2. What are the different reasons for microencapsulation?
3. Explain the formulation consideration of microencapsulation.
4. Explain the release mechanism of microcapsules.
5. Explain the different techniques of microencapsulation.
6. Explain the coacervation phase separation technique of
microencapsulation.
7. Explain the solvent evaporation technique of
microencapsulation.
8. Explain the polymerization technique of microencapsulation.
9. Explain the Wruster process of microencapsulation.
10. Write down the applications of microencapsulation.

51. Thank you…!!!