Solid Oral Dosage Forms - Capsules

Question 1

Advantages of hard gelatin capsules

Answer 1

• convenient to carry
• reasonably stable
• tasteless and easy to swallow
• soluble in body fluids at body temp.
• readily identifiable - colors
• can be used for modified drug release
• can be used for solids, semisolids and for materials which cannot be compressed
• Capsule in capsule delivery to separate incompatible materials (for 2 APIs)

Question 2

Disadvantages of hard gelatin capsules

Answer 2

• costly
• not suitable for hydrophilic materials
• not suitable for materials that are incompatible with gelatin
• may stick to the mucosa of the esophagus (gelatin absorbs moisture)

Question 3

Describe gelatin formation

Answer 3

1. Hydrolysis: Type A gelatin: obtained from animal skin by acid hydrolysis. Type B gelatin: obtained from bones by base hydrolysis
2. Gelatin is extracted with hot water and concentrated
3. Concentrated gelatin is chilled to produce gel
4. Gel is extruded to form strands
5. Strands are dried using fluidized bed then blended

Question 4

Shell materials for hard gelatin capsules

Answer 4

• Gelatin: non-toxic, soluble in biological fluids, good film-forming ability, mobile solutions at high concentration
• Water: used for extraction, final contents is 13-16% (<13% brittle shell -> difficult to cap, >16% softness and low rigidity -> will be deformed when capped)
• Color: water soluble dyes (erythrosine, indigo carmine and quinidine yellow) and water insoluble pigments (iron oxides and titanium oxides)
• Wetting agent - sodium lauryl sulfate
• Preservatives to prevent microbial growth

Question 5

Describe the manufacturing of shell

Answer 5

• Pairs of pins corresponding to bodies and caps of the capsules are dipped in heated (45-55C), air-free gelatin solutions containing the necessary additives
• Pins are rotated a few times to distribute the solutions evenly as they are withdrawn from the gelatin solution
• Cold air is blown on the rotating pins to firm up the gelatin shells
• Pins are passed through series of kilns for drying
• Bodies and caps are then removed from pins are rimmed to given lengths by rotating blades
• Caps placed on the bodies and packed

Operation is 24/7, producing 1m capsules/day

Question 6

Describe the capsule filling steps

Answer 6

1. Filling - caps are removed and bodies are filled -> caps replaced and filled capsules ejected
2. Sealing - prevent separation of the caps from the bodies; self locking, banding and heat welding
3. Cleaning - salt polishing, cloth dusting and brushing
4. Coating - film and enteric coating

Question 7

Advantages of soft gelatin capsules

Answer 7

• convenient to carry
• easier to swallow due to smaller size
• greater stability compared to hard gelatin capsules
• very accurate and uniform dosing for liquid formulations
• greater absorption and bioavailability
• flavored, elegant
• safety

Question 8

Disadvantages of soft gelatin capsules

Answer 8

• costly and sophisticated machines required
• not suitable for dry materials -> used only for solutions, semisolid and suspensions
• not suitable for solutions having high water contents
• not suitable for formulations with high pH (>7.5) (-> crosslinking) or low pH (<2.5) (-> hydrolysis of gelatin)
• drug can migrate from an oily vehicle into the shell

Question 9

Shell materials for soft gelatin capsules?

Answer 9

• Gelatin - mainly type B, 40% of the wet molten gel
• Water - 20-30% of wet gel (during gel preparation), after drying it should be 5-8%
• Plasticizers - add elasticity to the softgel shell for a good continuous film that does not break, 20-30% of the wet gel
• Preservatives
• Additives
• Colorants
• Opacifiers - produce an opaque shell -> prevent photodegradation of light sensitive material

Question 10

Describe the manufacturing of soft gelatin capsules

Answer 10

2 continuous gelatin sheets are produced on 2 rotating drums and are conveyed to 2 cylinders with matching dies rotating in the same direction. As the gelatin sheets come between the dies, the material to be filled is injected through a metering device and the sheet swell up to form capsules. Simultaneously, the pressure exerted by converging dies seal and cuts out the capsules. The finished capsules which fall on a conveyor belt are carried through rapid dryers where moisture is removed. Remaining moisture is removed by passing capsules through drying channels into which air is passed.

Question 11

What are the parameters to control during the manufacturing of soft gelatin capsules

Answer 11

1. Temperature: the heat available for capsule seal formation
2. Pressure: exerted between the 2 rotary dies -> soft shape and final cut-out from the gel ribbon
3. Timing: of dosing quantities of fill matrix into softgel during its formation

Question 12

What are the in-process testing for soft gelatin capsules

Answer 12

• Gel ribbon thickness
• softgel seal thickness at the time of encapsulation
• fill matrix weight and capsule shell weight
• softgel shell moisture level and softgel hardness after drying

Question 13

Types of fill materials for soft gelatin capsules

Answer 13

• Lipophilic liquids/oils: limited capacity to dissolve drugs; e.g. triglyceride oil
• hydrophilic liquids: e.g. high molecular weight polar liquids (PEG), water and ethanol can be incorporated at low levels <10%
• self emulsifying oils: a combination of a pharmaceutical oil and a non-ionic surfactant e.g. polyethylene sorbitan mono-oleate
• microemulsion and nanoemulsion systems: high capacity to solubilize drug compounds and retain the drug in solution even after dilution in the GI fluids

Question 14

Definition of hard gelatin capsules

Answer 14

An edible package made from gelatin/other suitable materials which is filled with medicines to produce a unit dosage mainly for oral use

Question 15

Formulation considerations for hard gelatin capsules

Answer 15

• Matrix components must be compatible with gelatin but must not react with it
• Matrix must not have high content of free moisture
• Unit dose must not exceed the capsule size
• Consistent release of active content
• Uniform content
• Additives may be added (diluents, disintegrants, glidants, lubricants, surfactants, absorbents)

Question 16

Materials for hard capsule filling

Answer 16

• Dry solids: powders, pellets, granules, tablets
• Semisolids: thermosoftening mixtures, pastes
• Liquids: Non-aqueous liquids (NO WATER)

Question 17

What is a soft gelatin capsules

Answer 17

It consists of a liquid/semisolid matrix inside a one-piece outer gelatin shell. Biphasic dosage form.

Question 18

Soft gelatin capsules can be formulated as

Answer 18

• Oral softgels containing solutions/suspensions released in the stomach
• Chewable softgels - flavored shell can be medicated
• Suckable softgels - contain flavored medicement
• Twist-off softgels - not for eating, for applying; have a tag to be snapped off to release contents

Question 19

Formulation considerations for soft gelatin capsules

Answer 19

• Matrix components must be compatible with gelatin
• Matrix components must have the capacity to dissolve and retain drug in solution in GI fluid
• Matrix components must have the ability to optimize the rate, extent and consistency of drug absorbed (consistent release of API)