Encapsulation Flashcards
What is encapsulation?
Process in which tiny particles or droplets are surrounded by a coating
What are the 2 types of encapsulation?
microencapsulation:
- reservoir type
- matrix type (disperse drug all over)
When is nanoencapsulation used?
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
When is microencapsulation used?
- reasonable payload
- hold nutrients, enzymes, cells, etc.
- offers protection, diffusion barrier
What is macroencapsulation?
- high payload possible
- consistent production quality
- multi-particulate drug delivery system
What are the properties of nanoencapsulation?
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
How are polymeric nanoparticles produced for viable commercial production?
Nanoporous membrane extrusion (NME)
Why encapsulate?
- protection against moisture, oxygen, light
- prolong shelf life (confer stability)
- Prevent premature release and pre-reaction
- Mask undesirable taste, odour, and/or colour
- Provide controlled release - rate, target, timed, delayed (zero order)
- Convert liquid into solid (ease of handling)
- Reduce flammability
- Improve safety and handling
provides isolation, entrapment structuration, protection or controlled release of a sensitive or reactive material (flavour, fragrance, bioactive) from surrounding/environment.
How does dripping/extrusion works?
- congeal: droplets from nozzle/orifice into inhospitable medium to cause coagulation/ cross-linking
- or vibrate; break liquid stream into droplets
How does coacervation works (liquid-based formation)? And what are the uses?
- 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.
How does emulsification works (liquid-based formation)? What are the uses/applications?
- 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
Why coating of cores containing active ingredients API is important in macroencapsulation?
- Modification of drug release: delayed/sustained release (0 order)
- Protection of drug: taste masking, moisture/gas barrier, UV protection, add colour
What are the different coated dosage form systems and its uses?
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
What are the advantages of controlled release systems?
- 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)
What are 5 coating processes for pharmaceuticals?
- Compression: specialised tablet press, with capability of multi-layer compression (tab-in-tab)
- Pan coating: popular and well-established method to coat tablets
- Air suspension: Wurster coating to coat small particles (e.g. pellets)
- Spray coating: spray dryers convert liquid feeds to dry powders (for coating)
- Melt coating: hot melt extrusion or spray congealing (prilling) (niche tech)
How to design sustained drug release pellet?
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
What are the steps for core production by extrusion-spheronisation? (for the drug-loaded pellets, not for the non-pareils)
- dry blending
- wet massing
- extrusion
- spheronisation
- drying
- coating
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)
- Bottom-spray - Wurster coating: for coating pellets (widely used); dry at top
- OR Side/centrifugal spray systems; very efficient coaters for particles
- OR top spray; often used for granulation rather than coating; coating efficiency is inferior to bottom or side spray systems
How does pellet coating systems with ‘envelope’ air works?
- 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
What are the properties of GIT? How does pellets interact with the GIT?
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
What are the uses of spray drying?
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
What are the advantages of spray drying?
- 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
How to prepare spray dried microparticles for suspensions and solutions?
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
What are the functional principles of spray drying?
Atomised droplets –> contacts hot drying gas –> dry surface forms (heat + evaporation of water) –> dry particle
solid shrivelled hollow cenosphere particle distribution
What are some nozzle designs for spray drying?
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)
What are the spray drying fundamentals in terms of particle size distribution?
Pressure nozzle atomization: narrow distribution)
Rotary atomizer: Intermediate distribution
2-fluid nozzle atomization (fountain): broader distribution
What is the concept of spray prilling (congealing)?
And what are the uses?
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
What are the two types of capsules?
Hard gelatin capsule
Soft gelatin capsule
What are the issues with capsules (soft and hard)?
- 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
What are the fill capacity of capsules (hard gelatin)?
- 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
What are some alternatives for non-protein based capsules (vegetarian capsules)?
- Hydroxyproplymethyl HPMC
- pullulan (Water soluble polysacc)
- HPMC and carrageenan
- alginate
How do we assess capsule quality?
- assay
- uniformity of dosage units
- disintegration
- dissolution
What kind of shapes and sizes soft gelatin capsules come in?
- round
- oval
- oblong
- tube
What are the advantages of softgel capsules?
- 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
What are some critical formulation tips when making soft capsules?
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?)
What should we take note for the bioavailability from capsules?
- 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
For a repeat action preparation (sustained dose), what kind of coating does pellets have?
Pellets with pulsatile release coatings
e.g. prompt dose –> first sustaining dose –> second sustaining dose
What are some methods for multiparticulate drug delivery system?
- 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)
What is the difference between spray drying and spray priling (congealing)?
spray drying involves hot drying gas
spray congealing involves cold air
What are the machines for the production of capsules?
hard gelatin capsules: FEC40 aka Fette Compacting
soft gelatin capsules: soft gel technology
What are some techniques for encapsulation?
- dripping/extrusion
~ congealing
~ vibration
liquid-based formation:
- coacervation
- emulsification
