Encapsulation and capsules Flashcards
benefits of using pellet coating systems with envelope air
Minimise local overwetting
Pattern spray dispersion
Protect the spray (prevent particles from getting stuck on the nozzle)
Microencapsulationn
Process which tiny particles/droplets surrounded by coating
2 types:
- Reservoir: core covered by shell – drug release controlled by barrier property of shell
- Matrix: consist of drug dispersed in matrix – drug release controlled by surface area available for release – release of drug is 1st order, thus formulation must be able to erode to form a pseudo zero order system
Types of encapsulation technologies:
nano: imaging phase contrast, injectables, vaccine
micro: reasonable payload, holding nutrients, enzymes, cells – offers protection, diffusion barrier
Macro: high payload possible, consistent production quality, multi-particulate drug delivery system
Methods for nanoencapsulation
Top down:
- milling/shreading/grinding
- homogenisation/extrusion
Bottom up methods:
- Antisolvent precipitation
- Coacervation (temp/salt/pH): liquid liquid phase separation
- Drying
- formation of inclusion complex
- fluid gel particle formation (shear and gelation)
traits of nanocapsules:
low payload, limited protection and stability, highly permeable
Encapsulation materials:
Particles
Modified biopolymers
Synthetic (co) polymers
low MW molecules
Functional ingredients frequently encapsulated:
Probiotics sensitive fatty acids antioxidants vitamins flavours, aromas, colorants drug like components
Release trigger of capsules:
pH Mechanical stress Enzymes Ultrasound Temperature Ionic strength Light
Encapsulation techniques:
Emulsion based: pickering, self-assembling, layer by layer Spray drying dipping (slide 10) fluid bed coating extrusion coacervation solvent change/removal
Need for encapsulation
- protection against moisture, oxygen and light
- prolonged shelf life (confer stability)
- prevent premature release and pre reaction
- mask undesirable taste, odour and/or colour
- provide controlled release
- convert liquid into solid – for handling
- Reduce flammability
- Increase safety and handling
Dipping/extrusion:
Dripping of droplets of pellet material into a medium where the material will not be soluble in using a nozzle – air used to break up the string of liquid
can have formation of different sizes
coacervation:
Separation of liquid phase of coating material from polymeric solution and ecapsulating core particles by uniform polymeric layer
Traits of coacervation:
Well established method, batch process
Require skillful operator
often contains gelatin
use in: carbonless paper, pesticide fragrances, liquid crystals, detergents, paint stabilisers, adhesives
Emulsification method:
Formationn by water-organic solvent mixtures with surfactants
Uses of emulsification method:
protect drug from environment Mask unpleasant taste and odour decreased drug volatility decreased gastric irritation by drug separates incompatible components control drug release production of chemoembolisation agents production of microbioreactors
Macroencapsulation:
Coating of cores containing active ingredient
- modification of drug release (delayed/sustained)
- Protection of drug (taste masking, moisture/gas barrier, UV protection, add colour)
Coated dosage form systems:
Coated particle: taste maskig, stability enhancement
coated pellet: multiparticulate drug delivery system, multi unit pellet system tablet
coated tablet: decorative and identification, eteric coated, sustained release coated, osmotic pump
coated capsule : non common, enteric/prolonged release
Traits of controlled release systems:
- Extended daytime and nighttime activity of drug
- Potential for reduced incidence of side effects
- Reduced dosage frequency
- Increased patient compliance
- Potential lower daily cost to patient (fewer dosage units)
Coating process for pharmaceuticals:
- Coating: specialised tablet press with capability of multilayer compression
- Pan-coating: popular and well established method to coat tablets
- Air suspension: wurster coating used for coating pellets
- spray coating: spray dryers used to convert liquid feeds to dry powders
- melt coating: hot melt extrusion/spray congealing
Design strategies:
- non pareils used as cores to be layered with drug and then coated with diffusion barrier polymer coat
- Drug loaded pellets prepared by extrusion spheronisation then overcoated with diffusion barrier polymer coat
Production steps by extrusion-spheronisation:
- dry blending
- wet massing
- extrusion
- spheronisation
- drying
- coating
Fluid bed drying and coating types:
Top spray
bottom spray
side spray
drying
Top spray coating:
use countercurrent system
- air moves upwards – smaller particles preferentially coated
- used more for granulation than coating – coating efficiency inferior to bottom/side spray systems
Bottom spray system:
draw in pellets from the side and all will be effectively coated efficiently as particles are effectively in a queue
Side spray coating:
Efficient coaters for paticles and air flow will swirl pellets around
Pellet coating systems with ‘envelope’ air
3 component nozzle
Air around spray nozzle extend spray into coating substrate bed
movement of particles is spiral
Repeat action preparations:
pellets with pulsatile release coatings for sustained overall response
Limitations of GIT on sustained release
absorptive phase max 8-10h – at best BD dosing
pellets can pass closed pylorus port and thus drug release will not be dependent on gastric emptying time
Spray drying:
convert solutions, suspension/emulsions to dry powders in a 1 step process
Advantages of spray drying:
highly efficient and versatile
fast and continuous drying process
can be established on large industrial scale
liquid can be converted to dry form – reduced volume
allow for ease of dosing, handling and transport
improved chemical and biological stability
defined shape and size
porus and high specific surface for easy dissolution
Preparation of spray dried microparticles:
- spraying of suspensions: insoluble active in solution of shell material
- Active and shell material added as liquid
functional principle of spray drying:
- atomised droplets added and comes into contact with hot drying gas
- dry surface formed
- Particle type formed:
- Solid particle
- shrivelled particle
- hollow particle
- cenosphere
- particle distribution
nozzle designs for spray drying
Two-fluid (air+feed) – largest particle size distribution
Three-fluid (2 samples+air)
Ultrasonic (vibration of nozzle)
Pressure – smallest particle size distribution
Rotatory atomiser (cooling air, feed, rotating spindle, purge gas)
Examples of spray dryers:
laboratory
small scale, pilot
pilot scale small
production scale
Spray prilling (congealing)
Cold air used to dry – confined to smaller sizes
uses of spray prilling:
prepare meltable powders (lubricants) , taste masking, controlled release products
0.2-1.5 mm range
Issues with capsules:
Gelatin used as raw material
- animal protein – religious concerns, association with animal diseases
- moisture sensitive
- properties may change with adsorbed constituents
Fill capacity of capsules (hard)
fill weight depends on tapped density (size 000(1.36 mL)-5 (0.15 mL))(largest to smallest)
Size 2 most commonly used: 0.37 mL
capsule fill weight = tapped density * capsule volume
can have self-locking mechanism
Good fill depends on good flow properties of feed
Non-protein based capsules (alternatives to gelatin)
hydroxyproplymethyl cellulose (HPMC)
Pullulan
HPMC and carrageenan
Alginate
Tests for capsule quality:
Hard gelatin capsules:
- Assay (quality of the capsule itself) – moisture permeability
- uniformity of dosage units
- disintegration
- dissolution
Traits of soft gelatin capsules:
- no compression stage, can contain poorly compressible drug
- liquid fill avoid problems with powder flow and mixing
- avoid oxygen/moisture degradation of drug during long term storage
- For poorly water soluble drugs in liquid vehicle emulsified in GIT as fine droplets
Fills avoided in soft gelatin capsules:
- Emulsions (may crack in capsule)
- Surfactants (affect gelatin integrity)
- pH<2.5 (gelatin hydrolyses)
- pH > 7.5 (tanning effect on gelatin)
- Aldehydes (forms cross linking with gelatin and may have tanning effect)
Bioavailability from capsules:
Dissolution of gelatin shell disperses content into intestinal liquid – bioavailability should be good (similar to liquid, powder, granule preparations)
Discharge of capsule content depends on flow of materials within – problematic for hydrophobic materials – need to add surface active agent to aid wetting/discharge
