The merits of filling hard gelatin capsules with liquids is usually compared to soft gelatin capsules (softgels)  There are significant differences between the dosage forms but they should be viewed as complementary rather than competing technologies. It is perfectly possible to switch between the two formats as well.  The formulation usually dictates the most appropriate capsule type, but in cases where the formulation allows a choice, hard capsules have several advantages over softgels:

• Water Content - The softgel shell has a far higher water content  than the hard capsule shell which may not be acceptable for moisture sensitive products.

• Placticisers - Softgels contain placticisers (usually glycerol or sorbitol) which can migrate into the capsule content or can aid migration of the fill into the shell. The gelatin used in hard capsule shells contains no plasticiser.

• Fill Vehicles - Thermo softening vehicles (melting at above 35 degrees C) are not acceptable for softgel filling. Hard capsules can be filled at up to 75 degrees C offering a wider range of suitable excipients, particularly for controlled release formulations.

• Microbial Growth - Softgels are more susceptible to microbial growth due to higher moisture content.

• Shell permeability - Softgels are more susceptible to moisture and gas transmission and can be an issue to oxidation sensitive products. This is caused mainly by the presence of plasticisers in softgels which create channels in the shell that are larger than those found in hard capsules.

• Cost - Softgel filling speeds are slow (30k/hour) and tray drying can take from days to weeks.  For hard capsules the separate cost of purchasing the capsule shell must be factored in, but is off-set by processing efficiencies and higher filling speeds (40-50k/hour).  In general, the costs of softgels and hard capsules are comparable.

• Coating - Hard capsules are generally regarded as being easier to coat (eg. enteric coating) than softgels.

• Manufacturing Capacity - Softgel manufacturing capacity is limited to a relatively small number of manufacturers, mainly due to the expensive cost of the equipment.  Hard Shell technology is widely available with contract manufacturers and it is a relatively straight forward process to transfer the technology inhouse.

• Intellectual property of shell - Liquid formulations may require a formulation of the softgel shell itself.  If this is contracted out to a softgel manufacturer, intellectual property rights to the shell typically remain with the contract manufacturer, therefore limiting the possibility of changing manufacturers.  This is not applicable for hard capsules which do not require reformulation of the shell.

• Materials and development timelines - Less materials are required to develop a hard capsule product (under 1kg of drug substance)  This is particularly important for early clinical development, where the availability of the drug is usually restricted.  Development timelines are generally much shorter as well.