Encapsulation

Question 1

What is encapsulation?

Answer 1

Process in which tiny particles or droplets are surrounded by a coating

Question 2

What are the 2 types of encapsulation?

Answer 2

microencapsulation:

1. reservoir type
2. matrix type (disperse drug all over)

Question 3

When is nanoencapsulation used?

Answer 3

1nm-1um
~ imaging - phase contrast
~ injectable drug delivery systems
~ vaccine
~ bactericides/ microbiological uses

e.g. Silver: Preservatives, for disinfectants
Gold - inert, once in particle; change surface pprty stick onto surfaces; inc phase contrast when doing imaging

Question 4

When is microencapsulation used?

Answer 4

• reasonable payload
• hold nutrients, enzymes, cells, etc.
• offers protection, diffusion barrier

Question 5

What is macroencapsulation?

Answer 5

• high payload possible
• consistent production quality
• multi-particulate drug delivery system

Question 6

What are the properties of nanoencapsulation?

Answer 6

Properties: low payload, limited protection/stability, highly permeable

Deliver small amt of active; tend to be very sensitive/ difficult to manage
Produce small scale and need to be protected/stored at low temp to prevent degradation

If highly potent molecule/bioactive e.g. Antigen or some mRNA - stability is a problem
It is also permeable

Question 7

How are polymeric nanoparticles produced for viable commercial production?

Answer 7

Nanoporous membrane extrusion (NME)

Question 8

Why encapsulate?

Answer 8

1. protection against moisture, oxygen, light
2. prolong shelf life (confer stability)
3. Prevent premature release and pre-reaction
4. Mask undesirable taste, odour, and/or colour
5. Provide controlled release - rate, target, timed, delayed (zero order)
6. Convert liquid into solid (ease of handling)
7. Reduce flammability
8. Improve safety and handling

provides isolation, entrapment structuration, protection or controlled release of a sensitive or reactive material (flavour, fragrance, bioactive) from surrounding/environment.

Question 9

How does dripping/extrusion works?

Answer 9

• congeal: droplets from nozzle/orifice into inhospitable medium to cause coagulation/ cross-linking
• or vibrate; break liquid stream into droplets

Question 10

How does coacervation works (liquid-based formation)? And what are the uses?

Answer 10

• manipulation of pH, temp, solubility, ionic interactions
• separation of liquid phase of coating material from a polymeric solution and encapsulating the core particles by a uniform polymeric layer
  e. g. gelatin-gum; gelatin-acacia; gelatin-sodium alginate
• well-established batch process
• require skillful operatory/operation
• often contains gelatin (others: caesin, soy proteins, chitosan, starches, gums, etc.)

Use: carbonless paper, pesticide, fragrances, liquid, crystals, detergents, paint stabilisers, adhesives, etc.

Question 11

How does emulsification works (liquid-based formation)? What are the uses/applications?

Answer 11

• utilisation of surfactants and surface activity (emulsion-based)
• formation by water-organic solvent mixtures with surfactant
  e. g. sodium alginate soln in iso-octane + surfactants, hardened using calcium chloride (to form a cross-linked matrix system)

Applications:

• protects drug from environment
• masks unpleasant taste and odour
• reduces drug volatility
• reduces gastric irritation by drug
• separates incompatible components
• controls drug release
• produces chemoembolization agents
• produces microbioreactors

Encapsulate cells; removal of toxic pollutants e.g. Mercury, if use calcium alginate microsphere, calcium ion exchange with mercury

Question 12

Why coating of cores containing active ingredients API is important in macroencapsulation?

Answer 12

• Modification of drug release: delayed/sustained release (0 order)
• Protection of drug: taste masking, moisture/gas barrier, UV protection, add colour

Question 13

What are the different coated dosage form systems and its uses?

Answer 13

100microns and above

Coated particle: taste masking, stability enhancement

Coated pellet: multi-drug delivery system; multi-unit pellet system (MUPS) tablet

Coated tablet: decorative & identification; enteric-coated; sustained release coated; osmotic pump

Coated capsule: not common, enteric release, prolonged-release

• release of drug in planned, predictable, slower-than-normal manner
• drug delivers at planned and controlled rate

Question 14

What are the advantages of controlled release systems?

Answer 14

• Extended daytime and night-time activity of the drug
• Potential for reduced incidence of side effects
• Reduced dosage frequency
• Increased patient compliance
• Potential lower daily cost to patient (fewer dosage units used)

Question 15

What are 5 coating processes for pharmaceuticals?

Answer 15

1. Compression: specialised tablet press, with capability of multi-layer compression (tab-in-tab)
2. Pan coating: popular and well-established method to coat tablets
3. Air suspension: Wurster coating to coat small particles (e.g. pellets)
4. Spray coating: spray dryers convert liquid feeds to dry powders (for coating)
5. Melt coating: hot melt extrusion or spray congealing (prilling) (niche tech)

Question 16

How to design sustained drug release pellet?

Answer 16

Diffusion barrier coating (outermost) and Drug layer: polymer and drug (middle) - application by fluid bed coating

Drug layer: polymer and drug and Nonpareil bead (sugar/ microcrystalline cellulose) (innermost) - Drug-loaded pellet may be prepared by extrusion-spheronisation

~ Nonpareils used as cores to be layered with drug, then overcoated with diffusion barrier polymer coat
~ Drug-loaded pellets are prepared by extrusion-spheronisation, then overcoated with a diffusion barrier polymer coat

Question 17

What are the steps for core production by extrusion-spheronisation? (for the drug-loaded pellets, not for the non-pareils)

Answer 17

1. dry blending
2. wet massing
3. extrusion
4. spheronisation
5. drying
6. coating

Question 18

How is fluid bed drying and coating carried out?

(2 layers for the nonpareils: first layer: drug and polymer; second layer: diffusion barrier coating)
( 1 layer for the drug-loaded pellets: outer layer: diffusion barrier coating)

Answer 18

1. Bottom-spray - Wurster coating: for coating pellets (widely used); dry at top
2. OR Side/centrifugal spray systems; very efficient coaters for particles
3. OR top spray; often used for granulation rather than coating; coating efficiency is inferior to bottom or side spray systems

Question 19

How does pellet coating systems with ‘envelope’ air works?

Answer 19

• three-component nozzle
• bottom spray or side spray
• spray onto pellet
• envelope air concept around spray nozzle extends spray into coating substrate bed and minimises local over-wetting; can be used to pattern spray dispersion; FlexStream side nozzle can be removed for cleaning during process run
• envelope air: prevents air from hitting the floor of the container, ensure spraying into pellets

Question 20

What are the properties of GIT? How does pellets interact with the GIT?

Answer 20

Pellets can pass closed pylorus port; not dependent of GER

~ Stomach: 1/3-3h transit time; 8L gastric juice, pH 1-3

~ SI: 2-7h transit time; 9L intestinal juice, pH 5-7.5

~ Colon: 20-36h transit time; 1L liquid juice; 0.15L liquid, pH 7.2

Tablet are larger needs to be break down before it escapes
Reduced GER requirements for pellets
But pellets must have a coat - coat will disintegrate in the stomach first

Question 21

What are the uses of spray drying?

Answer 21

Convert solutions; suspensions and emulsions to dry powders

Inhalation products

Highly efficient and versatile
Fast and continuous drying process
Stabilised on a large industrial scale

Question 22

What are the advantages of spray drying?

Answer 22

• reduce volume, liquid to dry form
• ease dosing, handling and transport
• improved chemical and biological stability
• defined shape and size
• porous and high specific surface, easy dissolution

Question 23

How to prepare spray dried microparticles for suspensions and solutions?

Answer 23

Spraying of suspensions: insoluble active a solution of shell material

Spraying of a solution: active and shell material as a liquid

coating of small particles: 10-200um

Question 24

What are the functional principles of spray drying?

Answer 24

Atomised droplets –> contacts hot drying gas –> dry surface forms (heat + evaporation of water) –> dry particle

solid
shrivelled
hollow
cenosphere
particle distribution

Question 25

What are some nozzle designs for spray drying?

Answer 25

2-fluid 3-fluid Ultrasonic (no air) Pressure (no air, liquid is pressurised) Rotary atomiser (no pressured air here, rotate at high speed) (10-12 thousand revolutions High speed Centrifugal force Liquid pass through slot and broken down)

Question 26

What are the spray drying fundamentals in terms of particle size distribution?

Answer 26

Pressure nozzle atomization: narrow distribution) Rotary atomizer: Intermediate distribution 2-fluid nozzle atomization (fountain): broader distribution

Question 27

What is the concept of spray prilling (congealing)? And what are the uses?

Answer 27

Uses COLD air instead of hot air Hot melt spray in cold air E.g. Palm oil stearic acid - for food and pharma products, also cooling, chilling, and congealing - confined to 'smaller' sizes (compared to fertilisers/chemical products) with d50 in 200-1500um (0.2-1.5mm) range Use: preparing meltable powders (lubricants); taste masking, controlled release products

Question 28

What are the two types of capsules?

Answer 28

Hard gelatin capsule | Soft gelatin capsule

Question 29

What are the issues with capsules (soft and hard)?

Answer 29

- Gelatin is an animal protein; religious sensitives, objections; may be associated with animal disease, animal rights, green-house gas - moisture-sensitive - properties may change with adsorbed constituents e.g. aldehydes

Question 30

What are the fill capacity of capsules (hard gelatin)?

Answer 30

- Sizes: 5(0.13); 4(0.20); 3(0.27); 2(0.37); 1(0.48); 0(0.67); 00(0.95); 000(1.36) ( ) vol in ml Popular sizes: 0-4 Can have self-locking mechanisms Capsule fill weight depends on tapped density **Capsule filled wt = Tapped Density x Capsule Volume** Good fill depends on good flow properties

Question 31

What are some alternatives for non-protein based capsules (vegetarian capsules)?

Answer 31

- Hydroxyproplymethyl HPMC - pullulan (Water soluble polysacc) - HPMC and carrageenan - alginate

Question 32

How do we assess capsule quality?

Answer 32

- assay - uniformity of dosage units - disintegration - dissolution

Question 33

What kind of shapes and sizes soft gelatin capsules come in?

Answer 33

- round - oval - oblong - tube

Question 34

What are the advantages of softgel capsules?

Answer 34

- no compression stage, can contain poorly compressible drug - liquid fill avoids powder flow and mixing problems - avoid O2 or moisture degradation of drugs during long term storage; protected by gelatin shell - for poorly water soluble drugs, in a liquid vehicle, emulsified in GIT as fine droplets

Question 35

What are some critical formulation tips when making soft capsules?

Answer 35

When filling matrix, should avoid: - emulsions, may crack (prefer medium W/O emulsions; as water will dissolve with gelatin O/W not preferrable) - Surfactants (high); affect gelatin integrity - pH <2.5, hydrolysis of gelatin - pH >7.5, tanning effect on gelatin, insolubility - aldehydes, cross-linking, tanning effect (darker; pigments released?)

Question 36

What should we take note for the bioavailability from capsules?

Answer 36

- Dissolution of gelatin shell (puncturing) quickly disperses content into the intestinal liquid and bioavailability should be good, similar to liquid or powder/granule preparations - discharge of capsule content depends on flow of materials within, can be problematical for hydrophobic materials --> thus, add surface active agent to aid wetting and discharge

Question 37

For a repeat action preparation (sustained dose), what kind of coating does pellets have?

Answer 37

Pellets with pulsatile release coatings | e.g. prompt dose --> first sustaining dose --> second sustaining dose

Question 38

What are some methods for multiparticulate drug delivery system?

Answer 38

- extrusion-spheronisation (drug-loaded pellets) - fluid bed drying and coating (for the layers: diffusion barrier coating and drug layer for nonpareils) - pellet coating systems with 'envelope air' (seen in bottom and side spraying)

Question 39

What is the difference between spray drying and spray priling (congealing)?

Answer 39

spray drying involves hot drying gas | spray congealing involves cold air

Question 40

What are the machines for the production of capsules?

Answer 40

hard gelatin capsules: FEC40 aka Fette Compacting | soft gelatin capsules: soft gel technology

Question 41

What are some techniques for encapsulation?

Answer 41

- dripping/extrusion ~ congealing ~ vibration liquid-based formation: - coacervation - emulsification