Soft-Shell Capsules Flashcards
Soft shell capsules are hermetically sealed. What does this mean?
Airtight
What are the main characteristics of soft shell capsules?
- made of gelatin, water and a plasticizer (like HS capsules)
- opaque or transparent
- colouring agents can be added
- flavouring agents can be added
- can be coated to delay release
- water content should be insufficient to allow microbial growth, preservatives not normally added
What are soft shell capsules used to encapsulate?
- liquids (non-aqueous)
- semi-solids
What is the fill temperature of hard shell and soft shell?
Hard: <70 degrees
Soft: <35 degrees
Describe the effectiveness of soft shell capsules in terms of barrier.
Less effective barrier to water, light and oxygen compared to hard shell
List the advantages of soft shell capsules
- increased bioavailability due to improved absorption
- easy to swallow
- acceptable to patients
- good organoleptic properties
- avoids issues linked to handling powders
- liquid flow easier to predict and control
- improved stability
List the disadvantages of soft shell capsules
- manufacturing can be expensive
- specialist manufacture equipment required
List the main ingredients used in soft-shell capsules
- Gelatin (mainly type B)
- plasticizer
- additives
What bloom strength is used for gelatin?
150g
stronger strength would increase production cost
What is the use of plasticizers and what are common ones?
15-30 wt% used, make the shell flexible and elastic
- glycerol (glycerin)
- sorbitol, mannitol, maltitol
- propylene glycol
- low MW propylene gylcol
may affect disintegration, dissolution and stability
What can opacifying agents be used for?
protects contects and light-induced degradation
How do the shells provide some protection against oxygen?
Thickness of shell
If contents of shell are susceptible to oxidation, what should be done?
- plasticizer conc should be kept low
- capsules should be stored in cool, dry place
What can happen to shells in a high humidity environment?
become soft and sticky
What can happen to shells in a low humidity environment?
become hard and brittle
What should moisture content be for contents susceptible to hydrolysis?
low moisture content, especially if drug dissolved or dispersed in an oily vehicle
Discuss capsules to be swallowed whole, chewable capsules, suckable capsules and meltable capsules
Swallowed whole
- with a glass of water
- disintegration expected in stomach
Chewable
- chewing triggers drug release
- drug may be added to shell
- organoleptic properties important
Suckable
- shell contains medicant
- inside is empty or contains suitable liquid
Meltable
- pessaries or suppositories
What can softgel capsules be filled with?
- solutions
- suspensions
- emulsions
List softgel capsule imcompatabilities
- high water content
- very high solid content
- large proportion of hygroscopic ingredients
- high conc of various salts
- very high or low pH
- high conc of solvents eg ethanol
- high viscosity eg molasses
What are the considerations when formulating a softgel capsule filling?
- solubility of drug in chosen vehicle
- how quickly contents will disperse in GIT
- possible compatability issues with shell
- possibility of optimising drug absorption and bioavailability
How can lipophilic fill formulations be prepared?
use:
- free fatty acids
- fatty acid esters derivatives of hydrophilic compounds
- triglycerides
Simple formulation: drug solubilised or suspended in triglycerides. This is a suitable for a number of agents inc. potent drugs and/or lipophilic drugs (logP > 4)
Not all drugs will be soluble in long-chain triglycerides. What can you use as an alternative?
- medium chain triglycerides
- free fatty acides
What must be ensured in a suspension?
that it is homogeneous, to ensure dose uniformity
What are pre-concentrates?
Self-emulsifying systems, capsule is filled with oil phase
final emulsion will be formed in situ in intestines, once capsule contents are released and mix with the aqueous fluids in the small intestine
What are the advantages of pre-concentrates?
- improved drug solubility
- high surface area of resting micro or nanoemulsion
- rapid diffusion out of oil phase into intestinal fluids
- improved pharmacokinetics
Describe the use of hydrophilic liquids and give an example
Suitable polar, non-aqueous vehicles should have a MW large enough to allow the preparation of a solution or suspension
Eg: Poly(ethylene glycol) 400 Da
Why is viscosity important of a hydrophilic liquid?
it will affect liquid flowand how easy it is to fill the capsules
Why should lower MW solvents (such as ethanol) be used at lower concs (<10%) only?
To avoid destabilising the gelatin shell
Can highly hygoscopic solvents be used in a hydrophilic liquid?
No
What can affect the dissolution rate of soft-shell capsules?
Changes in:
- polymorph
- particle size
- due to Otswald ripening in suspensions or emulsions
- crystalline state of a drug formulated as a suspension
- solubility of a drug solubilised with the help of hydrophilic solvent(s) or co-solvent(s)
- upon release they will mis easily with aqueous fluids potentially triggering the precipitation of the drug
- can be trigerred by migration of water from shell into capsule
What can be assessed during the manufacturing process?
- thickness of gelatin film
- sealing of capsules (absence of leaks)
- filling weight and shell weight
- moisture content and hardness after drying
What can be assessed after the manufacturing process?
- uniformity of content
- dissolution
- disintegration
