1. Prepared by: Sabrina Rahman Archie

2.  Microencapsulation is a process by which solids, liquids or even gases may be encapsulated into microscopic size ranging from several tenths of 1  to 5000  in size through the formation of thin coatings of wall material around the substance being encapsulated.

3.  Microencapsulation provides the means: Of converting liquids to solids Of altering colloidal and surface properties Of providing environmental protection Of controlling the release characteristics or availability of coated materials.

4.  For masking the taste of bitter drugs. (Acetaminophen Tab.)  To facilitate selective sorption. (adsorbent activated charcoal)  To prepare sustained action dosage forms. (Progesterone)  To reduce gastric irritation. (KCl)  For separating the incompatible ingredients. (Aspirin Tab.)  To prevent volatilization of volatile substances. (Menthol)

5.  In permselectivity of enzyme, substrate and reaction products. (Urease)  To protect drugs from moisture and oxidation. (Vit. A palmetate)  In stabilization by conversion of dosage form i.e. liquid to solid. (Liquid crystals)  In new formulation concepts for creams, ointments, aerosols, dressings, plasters, suppositories and injectables.  In various pharmaceutical related areas such as hygiene, diagnostic aids and medical equipment design.

6.  Incomplete or discontinuous coating.  Inadequate stability or shelf life of sensitive pharmaceuticals.  Non-reproducible and unstable release characteristics of coated products.  Economic limitations.

7.  Microencapsulation involves a basic understanding of the general properties of microcapsules, such as: The nature of the core and coating materials Stability and release of coating materials Methodology of microencapsulation

8.  Core Materials:  Core material is nothing but specific material to be coated, can be liquid or solid in nature.  Liquid core can be dispensed or dissolved material.  The solid core can be a mixture of active constituents, stabilizers, diluents, excipient and release rate retardants or accelerators.

9. Core material CharacteristicsPurpose of encapsulation Dosage form Acetaminoph en Slightly water soluble solid Taste maskingTablet AspirinSlightly H 2 O soluble solid Separation of incompatibles Tablet,Capsule MentholVolatile solution Reduction of volatility Lotion ProgesteroneSlightly H 2 O soluble solid Sustained release Varied KClSlightly H 2 O soluble solid Reduced gastric irritation Capsule Activated charcoal AdsorbentSelective sorption Dry powder Vitamin A palmitate Non volatile liquid Stabilization to oxidation Dry powder

10. Typical coating properties such as  cohesiveness  permeability  moisture sorption  solubility  stability and  clarity -must be considered in the selection of the proper microcapsule coating material.

11.  Criteria: The coating materials should: Be capable of forming a film that is cohesive with the core material Be chemically compatible Non reactive with the core material Provide the desired coating properties such as strength, flexibility, impermeability, optical properties and stability.

12.  Water soluble resins: Gelatin, Starch, Polyvinylpyrrolidone, Carboxymethylcellulose, Methylcellulose, Polyvinyl alcohol and Polyacrylic acid.  Water insoluble resins: Ethylcellulose, Polyethylene, Polymethacrylate, Polyamide, Ethylene-Venyl acetate, silicones and cellulose nitrate.  Waxes and lipids: Paraffin, Beeswax, Stearic acid, Stearyl alcohol and Glyceryl stearates.  Enteric resins: Shellac, Cellulose acetate phthalate and Zein.

13.  Three important fields of current microencapsulation application are:  The stabilization of core materials: Microencapsulated Vit. A palmitate remains stable for a long period of time when preserved in 45 0 C at 75% R.H. On the other hand, un-capsulated Vit. A palmitate loses stability within 7 – 15 days when preserved in 45 0 C at 75% R.H. 

14.  The release of core materials:  Release of core materials depends on the following factors:  The permeability of the coating to the extraction fluid.  The dissolution rate of the core material  The coating thickness  The concentration gradient existing across the coating membrane.

15.  The release of core material or disruption of the coating can occur by pressure, shear or abrasion forces, any of which affords a release mechanism.  Two release characteristics are illustrated as: Release of aspirin is accomplished by a leaching or diffusion mechanism from the inert, p H insensitive ethyl cellulose coating.

16. Release of amphetamine is accomplished initially be a leaching action from the gastric fluid resistant coating then by the action of intestinal fluid in which the coating dissolves or disintegration.  Separation of chemically reactive ingredients within a tablet or powder mixture.

17.  Microencapsulation Processes and their Applicabilities: Microencapsulation process Applicable core material Approximate particle size. (  m) Air suspensionSolids 35 – 5000 Coacervation-phase separation Solids & liquids 2 – 5000 Multiorifice centrifugal Solids & liquids 1 – 5000 Pan coatingSolids 600 – 5000 Solvent evaporationSolids & liquids 5 - 5000 Spray drying & congealing Solids & liquids 600

18.  Basically the Process consists of:  The dispersing of solid, particulate core materials in a supporting air stream  The spray coating of the air suspended particles.  The design of the chamber and its operating parameters effect a re-circulating 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.

19.  Mechanism of action: 1. Within the coating chamber, particles are suspended on an upward moving air stream. During each pass through the coating zone, the core material receives in increment of coating material. 2. The cyclic process is repeated, depending on the purpose of microencapsulation, the coating thickness desired or whether the core material particles are thoroughly encapsulated.

20. 3. The supporting air stream also serves to dry the product while it is being encapsulated. Drying rates are directly related to the volume temperature of the supporting air stream.

21.  Factors: The following variables must be considered for efficient, effective encapsulation by air suspension techniques:  Density, Surface area, Melting point, Solubility, Friability, Volatility, Crystallinity and Flowability of the core material.  Coating material concentration  Coating material application rate.  Volume of air required to support and fluidizes the core material.  Amount of coating material required  Inlet and outlet operating temperatures

22.  Advantages:  The process has the capability of applying coatings in the form of solvent solutions, aqueous solutions, emulsions, dispersions or hot melts in equipment ranging in capacities from 1 to 990 pounds.  This technique is applicable to both microencapsulation and macroencapsulation coating processes.  Under idealized conditions, particles as small as 37  can be effectively encapsulated as single entities by this process.  Core materials comprised of micron or submicron particles can be effectively encapsulated by air suspension techniques.

23.  Disadvantages: o Generally the process is to be applicable only to the encapsulation of solid core materials. o Agglomeration of the particles to some larger size is normally achieved.

25.  Coacervation may be defined as a process that when solutions of two hydrophilic colloids are mixed under suitable conditions separation of liquid phase takes phase. This process consists of three steps:  Formation of three immiscible phases.  Deposition of the coating material on the core.  Rigidization of the coating.

26. 1. Three immiscible chemical phases which are formed mention below: ◦ A liquid manufacturing vehicle phase. ◦ A core material phase ◦ A coating material phase.  To form the three phases, the core material is dispersed in a solution of the coating polymer, the solvent for the polymer being the liquid manufacturing vehicle phase. The coating material phase, an immiscible polymer in a liquid state, is formed by utilizing one of the methods of phase separation coacervation

27. By changing the temperature of the polymer solution By adding a salt By adding a non-solvent By adding incompatible polymer to the polymer solution By inducing a polymer-polymer interaction

28.  2. Depositing the liquid polymer coating upon the core material is accomplished by controlled, physical mixing of the coating material and the core material in the manufacturing vehicle. Deposition of the liquid polymer coating around the core material occurs if the polymer is adsorbed at the interface formed between the core material and the liquid vehicle phase.

29.  The continued deposition of the coating material is promoted:  ◦ By a reduction in the total free interfacial energy of the system ◦ By the decrease of the coating material surface area during coalescence of the liquid polymer droplets

30.  Rigidizing the coating, usually by thermal, cross linking or desolvation techniques, to form a self sustaining microcapsule.  After complete process i.e. separation from the liquid manufacturing, vehicle and drying, the material appears as free flowing powder, which can be compressed as tablets, filled in hard gelatin capsules, suspended in a suitable liquid to from a suspension or may be converted into any other dosage form.

31.  The microencapsulation of relatively large particles by pan methods has become widespread in the pharmaceutical industry.  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 pan.  In some cases, final solvent removal is accomplished in a drying oven.

32.  Utilizes centrifugal forces to hurl a core material particle through an enveloping microencapsulation membrane.  This process is capable of encapsulating liquids and solids ( if the solids are dispersed in a liquid) of varied size ranges, with diverse coating materials.  Production rates of 50 to 75 pounds per hour have been achieved with the process.

33.  Spray Drying or spray congealing process are similar in that both involve dispersing the core material in a liquefied coating substances and spraying the core-coating mixture.  The principal difference between the 2 methods, is the means by which coating solidification is accomplished.  Coating solidification in the case of spray drying is effected by rapid evaporation of a solvent in which the coating material is dissolved.

34.  Coating solidification in spray congealing methods, is accomplished by thermally congealing a molten coating material or by solidifying a dissolved coating by introducing the coating-core material mixture into a non- solvent.  Removal of the non-solvent or solvent from the coated product is then accomplished by sorption, extraction or evaporation techniques.

35.  The microcapsule coating is dissolved 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 coating material mixture is dispersed in the liquid manufacturing vehicle phase to obtain the appropriate size microcapsule.  The mixture is then heated to evaporate the solvent for the polymer.

36.  This technique is applicable to a wide variety of liquid and solid core materials.  The core materials may be either water- soluble or water-insoluble material.

37.  The theory and practice of Industrial Pharmacy by Leon Lachman