Soft-Shell Capsules

Question 1

Soft shell capsules are hermetically sealed. What does this mean?

Answer 1

Airtight

Question 2

What are the main characteristics of soft shell capsules?

Answer 2

• 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

Question 3

What are soft shell capsules used to encapsulate?

Answer 3

• liquids (non-aqueous)
• semi-solids

Question 4

What is the fill temperature of hard shell and soft shell?

Answer 4

Hard: <70 degrees

Soft: <35 degrees

Question 5

Describe the effectiveness of soft shell capsules in terms of barrier.

Answer 5

Less effective barrier to water, light and oxygen compared to hard shell

Question 6

List the advantages of soft shell capsules

Answer 6

• 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

Question 7

List the disadvantages of soft shell capsules

Answer 7

• manufacturing can be expensive
• specialist manufacture equipment required

Question 8

List the main ingredients used in soft-shell capsules

Answer 8

• Gelatin (mainly type B)
• plasticizer
• additives

Question 9

What bloom strength is used for gelatin?

Answer 9

150g

stronger strength would increase production cost

Question 10

What is the use of plasticizers and what are common ones?

Answer 10

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

Question 11

What can opacifying agents be used for?

Answer 11

protects contects and light-induced degradation

Question 12

How do the shells provide some protection against oxygen?

Answer 12

Thickness of shell

Question 13

If contents of shell are susceptible to oxidation, what should be done?

Answer 13

• plasticizer conc should be kept low
• capsules should be stored in cool, dry place

Question 14

What can happen to shells in a high humidity environment?

Answer 14

become soft and sticky

Question 15

What can happen to shells in a low humidity environment?

Answer 15

become hard and brittle

Question 16

What should moisture content be for contents susceptible to hydrolysis?

Answer 16

low moisture content, especially if drug dissolved or dispersed in an oily vehicle

Question 17

Discuss capsules to be swallowed whole, chewable capsules, suckable capsules and meltable capsules

Answer 17

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

Question 18

What can softgel capsules be filled with?

Answer 18

• solutions
• suspensions
• emulsions

Question 19

List softgel capsule imcompatabilities

Answer 19

• 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

Question 20

What are the considerations when formulating a softgel capsule filling?

Answer 20

• 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

Question 21

How can lipophilic fill formulations be prepared?

Answer 21

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)

Question 22

Not all drugs will be soluble in long-chain triglycerides. What can you use as an alternative?

Answer 22

• medium chain triglycerides
• free fatty acides

Question 23

What must be ensured in a suspension?

Answer 23

that it is homogeneous, to ensure dose uniformity

Question 24

What are pre-concentrates?

Answer 24

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

Question 25

What are the advantages of pre-concentrates?

Answer 25

* improved drug solubility * high surface area of resting micro or nanoemulsion * rapid diffusion out of oil phase into intestinal fluids * improved pharmacokinetics

Question 26

Describe the use of hydrophilic liquids and give an example

Answer 26

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

Question 27

Why is viscosity important of a hydrophilic liquid?

Answer 27

it will affect liquid flowand how easy it is to fill the capsules

Question 28

Why should lower MW solvents (such as ethanol) be used at lower concs (\<10%) only?

Answer 28

To avoid destabilising the gelatin shell

Question 29

Can highly hygoscopic solvents be used in a hydrophilic liquid?

Answer 29

No

Question 30

What can affect the dissolution rate of soft-shell capsules?

Answer 30

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

Question 31

What can be assessed during the manufacturing process?

Answer 31

* thickness of gelatin film * sealing of capsules (absence of leaks) * filling weight and shell weight * moisture content and hardness after drying

Question 32

What can be assessed after the manufacturing process?

Answer 32

* uniformity of content * dissolution * disintegration