Capsules

Question 1

Why are capsules used?

Answer 1

*easier to formulate and manufacture than tablets
*some find easier to swallow
*suitable for drugs needing gastric protection
*suitable for taste masking

Question 2

What two types of capsules are there?

Answer 2

*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

Question 3

What are examples of advanced capsules?

Answer 3

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

Question 4

What is the most common capsule material?

Answer 4

Gelatin (hydrolysed collagen)
-stable in air when dry, decomposes when moist

Question 5

What is a vegetarian alternative to Gelatin?

Answer 5

Starch hydrolysate

Question 6

Why is Gelatin used?

Answer 6

*non toxic
*readily soluble in biological fluids at body temp
*good film former-strong and flexible
*when cooled, solution>gel

Question 7

What is the grade of gelatin characterised by?

Answer 7

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

Question 8

What can HGC’s be filled with?

Answer 8

*powders
*pellets
*granules
*tablets
*semi-solids/liquids

Question 9

How are solid HGC’s closed?

Answer 9

-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

Question 10

How are liquid filled HGC’s closed?

Answer 10

*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

Question 11

What property ensures homogeneity when filled powder capsules?

Answer 11

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)

Question 12

What size should powder particles be to have excellent flow properties?

Answer 12

> 150 um

Question 13

What methods are used to fill powders into HGC’s?

Answer 13

-punch filling by hand
- hand operated device
-auger filling
-vibration and/or compression assisted
-dosator
-dosing disk and tamping finger

Question 14

How is filling of powders into HGC’s carried out by using hand- operated devices?

Answer 14

*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

Question 15

How are HGC’s filled with powder using the Auger filling method?

Answer 15

*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

Question 16

How are HGC’s filled with powder using a vibration and/or compression assisted method?

Answer 16

*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

Question 17

Why use semi solids or liquids to fill HGC’s?

Answer 17

*avoids powder flow issues
*improved fill weight accuracy
*improves solubility and absorption
*for low dose/high potency drugs

Question 18

What type of semi solids are there?

Answer 18

*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

Question 19

What type of liquids are filled into HGC’s?

Answer 19

Non aqueous liquids

Question 20

What method is used to fill semi solids/liquids into HGC’s?

Answer 20

*Piston Filling
-volumetric dosing device
-prevent leakage
-semi solids filled as liquids by either heating or stirring
-after filling, revert to solid state

Question 21

What property of fluids affects variability of fill volume?

Answer 21

Viscosity
-too low; loss of liquid from splashing during filling
-too high; difficult to pump and problems in transfer from nozzle to cap body

Question 22

What range of viscosities are acceptable for liquid filling of HGC’s?

Answer 22

0.1-20 Pa.s

Question 23

What do you have to be careful that an excipient added to liquid filled HGC’s doesn’t effect?

Answer 23

Equilibrium moisture content (EMC)
HGC’s shells contain 13-16%
Too much makes shell brittle

Question 24

Name 3 differences between HGC’s and SGC’s.

Answer 24

*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

Question 25

What are advantages of using SGC’s?

Answer 25

*improved drug absorption for poorly soluble drugs
*patient compliance- easy to swallow, taste free
*higher product stability- protected from water and oxygen

Question 26

What are SGC’s shells composed of?

Answer 26

*low bloom strength Gelatin
*plasticiser
*water

Question 27

What plasticisers are used in SGC shells?

Answer 27

*glycerol
*sorbitol
NOTE- plasticiser allows polymer chains to slide, making polymer more flexible

Question 28

What methods are used to make soft gels?

Answer 28

*Rotary die method- fusion of ribbons
*Globex method-capillaries

Question 29

How is the rotary die method for SGC manufacture carried out?

Answer 29

*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

Question 30

What type of dyes are used in HGC’s and SGC’s?

Answer 30

*Azo dyes- (-N=N-) azo kinkage, sunset yellow (orange), allura red
*Indigo dyes- two I satin molecules joined by double bond. Indigo carmine (blue)

Question 31

What are examples of commonly used pigments?

Answer 31

Iron oxides- black, yellow, red (depends on oxidation state)

Question 32

What is an opacifier and what is an example?

Answer 32

Protects from light and conceals cap contents
Titanium dioxide

Question 33

Why are preservative needed in capsules?

Answer 33

Gelatin is a good medium for bacterium and fungal growth
Added during manufacture
-methylparaben
-sulphur dioxide