Solid Oral Dosage Forms - Capsules Flashcards
Advantages of hard gelatin capsules
- 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)
Disadvantages of hard gelatin capsules
- 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)
Describe gelatin formation
- Hydrolysis: Type A gelatin: obtained from animal skin by acid hydrolysis. Type B gelatin: obtained from bones by base hydrolysis
- Gelatin is extracted with hot water and concentrated
- Concentrated gelatin is chilled to produce gel
- Gel is extruded to form strands
- Strands are dried using fluidized bed then blended
Shell materials for hard gelatin capsules
- 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
Describe the manufacturing of shell
- 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- Pins are rotated a few times to distribute the solutions evenly as they are withdrawn from the gelatin solution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
Describe the capsule filling steps
- Filling - caps are removed and bodies are filled -> caps replaced and filled capsules ejected
- Sealing - prevent separation of the caps from the bodies; self locking, banding and heat welding
- Cleaning - salt polishing, cloth dusting and brushing
- Coating - film and enteric coating
Advantages of soft gelatin capsules
- 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
Disadvantages of soft gelatin capsules
- 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
Shell materials for soft gelatin capsules?
- 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
Describe the manufacturing of soft gelatin capsules
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.
What are the parameters to control during the manufacturing of soft gelatin capsules
- Temperature: the heat available for capsule seal formation
- Pressure: exerted between the 2 rotary dies -> soft shape and final cut-out from the gel ribbon
- Timing: of dosing quantities of fill matrix into softgel during its formation
What are the in-process testing for soft gelatin capsules
- 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
Types of fill materials for soft gelatin capsules
- 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
Definition of hard gelatin capsules
An edible package made from gelatin/other suitable materials which is filled with medicines to produce a unit dosage mainly for oral use
Formulation considerations for hard gelatin capsules
- 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)
