Capsules Flashcards
Why are capsules used?
*easier to formulate and manufacture than tablets
*some find easier to swallow
*suitable for drugs needing gastric protection
*suitable for taste masking
What two types of capsules are there?
*Hard Gelatin Capsules (HGC’s)- two piece system cap and body with locking device (indents outside/inside cap)
*Soft Gelatin Capsules (SGC’s)- one piece system
What are examples of advanced capsules?
Pulsatile capsules-
*Pulsincap system- insoluble capsule body with degradable plug (made of hydrophilic polymer). Lag time controlled by plug- pushed away by erosion- pulse of drug released from insoluble capsule
Can be dual drug
*Osmotic system- capsule with semi permeable membrane. Has osmotically active layer at bottom. When ingested, water drawn into layer-swells, pushes drug out of cap
What is the most common capsule material?
Gelatin (hydrolysed collagen)
-stable in air when dry, decomposes when moist
What is a vegetarian alternative to Gelatin?
Starch hydrolysate
Why is Gelatin used?
*non toxic
*readily soluble in biological fluids at body temp
*good film former-strong and flexible
*when cooled, solution>gel
What is the grade of gelatin characterised by?
It’s BLOOM STRENGTH-measure of gel rigidity (cohesive strength of cross-linkage between molecules)
(Definition- the weight in grams required to push a plunger with a set bottom diameter, a set distance into a 6.67% w/w Gelatin gel prepared in water and allowed to cook at 10°C for 16-18h.)
HIGH bloom strength=harder material+more viscous in solution
What can HGC’s be filled with?
*powders
*pellets
*granules
*tablets
*semi-solids/liquids
How are solid HGC’s closed?
-indentations that fit into each other
*Coni- Snap- tapered rim, air vents for air to escape, 6 dimples for pre lock
*Dbcaps- cap covers most of body
How are liquid filled HGC’s closed?
*Gelatin band sealing- dilute solution of Gelatin and colour pigment. Prevents leakage, reduces oxygen permeation
*Hydroalcoholic solvent seal- water/ethanol mixture sprayed on joint between cap and body, plus gentle heating to fuse and seal
What property ensures homogeneity when filled powder capsules?
Each ingredient including API should have a closely matching particle size distribution
Also helps avoid segregation
(Narrow size distribution means powder flow easy to predict)
What size should powder particles be to have excellent flow properties?
> 150 um
What methods are used to fill powders into HGC’s?
-punch filling by hand
- hand operated device
-auger filling
-vibration and/or compression assisted
-dosator
-dosing disk and tamping finger
How is filling of powders into HGC’s carried out by using hand- operated devices?
*empty capsules placed on loading tray
*loading tray placed into filler unit
*capsules rotated so capsule body is in filler unit
*loading tray removed
*top plate lifted to remove caps
*bodies filled
*too plate returned to cap them
How are HGC’s filled with powder using the Auger filling method?
*powder placed in hopper with rotating auger
*auger continuously feeds powder to capsule bodies
*amount of powder fed to bodies depends on: time capsule spends below hopper, rotation spread of auger and screw (auger) design
NOTE- powder bulk density can change over time (affecting fill volume)- adjust auger speed and rotation
How are HGC’s filled with powder using a vibration and/or compression assisted method?
*capsules placed on roasting turntable below powder bowl
*powder bowl has mesh floor
*vibrating device helps powder go through mesh to fill capsule body
NOTE: fill mass depends on rotation speed of turntable and strength of vibration
IF COMPRESSION USED
*capsule body overfilled and compressed by plunger
*scraper removed excess prior to capping
Why use semi solids or liquids to fill HGC’s?
*avoids powder flow issues
*improved fill weight accuracy
*improves solubility and absorption
*for low dose/high potency drugs
What type of semi solids are there?
*thermo-softening mixtures- filled in molten state (pumped and filled) and left to solidify- PEG 4000
*thixotropic mixtures- thin low viscosity by mixing, which form hard masses (high viscosity) upon standing when mixing (shearing) ceases. Filled as fluids, semi solid during storage
*pastes
What type of liquids are filled into HGC’s?
Non aqueous liquids
What method is used to fill semi solids/liquids into HGC’s?
*Piston Filling
-volumetric dosing device
-prevent leakage
-semi solids filled as liquids by either heating or stirring
-after filling, revert to solid state
What property of fluids affects variability of fill volume?
Viscosity
-too low; loss of liquid from splashing during filling
-too high; difficult to pump and problems in transfer from nozzle to cap body
What range of viscosities are acceptable for liquid filling of HGC’s?
0.1-20 Pa.s
What do you have to be careful that an excipient added to liquid filled HGC’s doesn’t effect?
Equilibrium moisture content (EMC)
HGC’s shells contain 13-16%
Too much makes shell brittle
Name 3 differences between HGC’s and SGC’s.
*SGC’s have a plasticised shell, HGC’s do not
*SGC’s are usually filled with non aqueous liquids or suspensions, HGC’s semi solids, solids and non aqueous liquids
*HGC’s are split manufacture- shells made in one operation and filled in other, SGC’s in one operation
What are advantages of using SGC’s?
*improved drug absorption for poorly soluble drugs
*patient compliance- easy to swallow, taste free
*higher product stability- protected from water and oxygen
What are SGC’s shells composed of?
*low bloom strength Gelatin
*plasticiser
*water
What plasticisers are used in SGC shells?
*glycerol
*sorbitol
NOTE- plasticiser allows polymer chains to slide, making polymer more flexible
What methods are used to make soft gels?
*Rotary die method- fusion of ribbons
*Globex method-capillaries
How is the rotary die method for SGC manufacture carried out?
*shell formulation melted
*ribbons of shell produced with defined width and thickness
*ribbons brought together between two rotating dies
*metered filling injected between ribbons at moment die forms ribbon pocket
*capsules sealed by pressure and heat
*collected, washed, dried
What type of dyes are used in HGC’s and SGC’s?
*Azo dyes- (-N=N-) azo kinkage, sunset yellow (orange), allura red
*Indigo dyes- two I satin molecules joined by double bond. Indigo carmine (blue)
What are examples of commonly used pigments?
Iron oxides- black, yellow, red (depends on oxidation state)
What is an opacifier and what is an example?
Protects from light and conceals cap contents
Titanium dioxide
Why are preservative needed in capsules?
Gelatin is a good medium for bacterium and fungal growth
Added during manufacture
-methylparaben
-sulphur dioxide
