Hard-shell Capsules

Question 1

What are the main two parts of a hard-shell capsule?

Answer 1

The cap-Shortest part of capsule
The body- Longest part of the capsule

Question 2

How do hard-shell capsules prevent contents from being leaked out?

Answer 2

The contents are generally filled into the body before the cap is snapped into place.

Question 3

What are the advantages of using capsules?

Answer 3

• They have longer shelf life than liquid dosage forms
• Simpiler formulation compared to tablets
• More convinient
• Tampering can be detected easily
• Good absorption profile

Question 4

What re the two types of gelatin made for hard-shell capsules, and how are they produced?

Answer 4

• Type A gelatin: the type of gelatin is produced through acid hydrolysis ( pH 1-3). The process can take up to 10 days.
• Type B gelatin: This type of gelatin is produced through basic hydrolysis and the process can take up to 3 months.

Question 5

After the gelatin is hydrolysed, what is it isolated as?

Answer 5

After hydrolysis, gelatin is isolated as a light amber-faintly yellow vitreous (glass-like), brittle, odourless and tasteless solid.

Question 6

What are the properties of fish gelatin?

Answer 6

Collagen can be extracted from fish.

Skin.bones and fins which are all by-products of the industry

Both cold adn warm fish can be used

Question 7

What is bloom strength and what is its range in hard-shell capsule?

Answer 7

• Bloom Strength: Provides info on the rigidity of a gelatin gel and corresponds to “ the force (g) needed to depress the surface of a gelatin gel 6.67% (w/w)) aged for 16-18 minutes at 10oC] by 4mm, using a flat bottomed plunger.
• The gelatin used in the manufacture of hard-shell capsules typically has a Bloom strength ca. 230-275 g.

Question 8

How is viscoity measured with gelatin solution?

Answer 8

Visocisty is typically measured using a U-tube viscometer, again with a 6.67% (w/w) gelatin solution. Values in the range of 3.3-4.7 mPas are used as shell material for hard capsules.

Question 9

Give 5 properties of gelatin capules?

Answer 9

• Clear, odourless, tasteless, good mechanical properties, readily dissolve in water at body temperature- but will swell and soften in water at room temperature
• Moisture content 13-16%- water acts as a plasticiser, maintaining film flexibility.
• The moisture content will vary in different environments
• Capsults will absorb water in high-humidity environments- The shell will become softer and more malleable
• Capsules will release water in low-humidity environments- Shell will become brittle and more prone to breakage.

Question 10

Which powders and APIs are incompatible with Gelatin capsules?

Answer 10

Hygroscopic powders, Deliquescent powders, Hydrolysis-prone APIs- API may absorb water from the shell which will affect both drug and capsule integrity.

Question 11

What is Cross-linking?

Answer 11

Cross-linking is the formation of strong chemical bonds between individual gelatin chains. The formation of those bonds is generally irreversible and can affect the performance of gelatin capsules in pharmacopoeial tests.

Question 12

What factors cause cross-linking?

Answer 12

• aldehydes and ketones
• ​oxidising agents
• metal ions
• sugars
• heat
• high/low humidity
• light

Question 13

What are the consequences of cross-linking?

Answer 13

• Low or incomplete cross-linking
• Delay in capsule disintegration

Question 14

How may you go about addressing consequnces to do with cross-linking?

Answer 14

You can add protease to the dissolution medium;

Pepsin- mild to moderate cross-linking

Pancreatin- mild cross-linking

Question 15

What is a sachet?

Answer 15

In terms of drug formulation, sachets will be used to deliver a small quantity of a medicine.

Question 16

What can you put in a sachet?

Answer 16

Dry solids

• Powders
• Granules

Liquids

Question 17

What are the advantages of using satchets for patients?

Answer 17

• Convinience
• Available as a unit dose
• Easy to prepare
• Easy to swalllow, compared to tablets/capsules

Question 18

What are the advantages of satchets for pharmaceutical companies?

Answer 18

• Relative ease of manufacture
• Likely using a similar powder mixtures (drug and excipients) to tablets and capsules
• Variable dose easily made by adjusting filled volume
• Cost benefits
• Potentially less costly to ship compared to liquid dosage forms
• Increased shelf-life, similar to other solid dosage forms

Question 19

What are the advantages of using HPMC?

Answer 19

Plant source

Generally good stability

Low moisture content: 2-6%

Less hygroscopic than gelatin capsules

Less sensitive to low-moisture environments vs. gelatin

Lower risk of moisture being transferred from the shell to the capsule content

Fewer incompatibility issues vs. gelatin

May not be the best choice for encapsulation of drugs/excipients sensitive to oxydation

Production process may vary from one manufacturer to the other

Use of gelling agents can slow the disintegration/dissolution of the capsule

Different manufacturers may lead to different release profiles

Question 20

What is the main advantage of Pullalan use in hard-shell capsules?

Answer 20

Good barrier to oxygen

• Alternative for encapsulation of APIs sensitive to oxydation

Question 21

Give the 4 unit processing involved in formulatiomn for encapulation.

Answer 21

Particle size reduction

• To ensure homogenous mixing and limit the risk of demixing

Mixing- as required

Filling of capsules

Packaging of finished product

The excipient load was the lowest for the capsules

Question 22

What are the requirments for powder filling?

Answer 22

The powder filling must have the right properties to ensure that

Capsules are filled uniformly

The final product is stable

• Incompatibilities should be avoided

The drug is released and available for absorption within the expected time frame

The final product comply with pharmacopoeial quality requirements

As expected, the powder will need to have good flow properties in order to meet these conditions.

Adhesion should be avoided

Some cohesion may be desirable for plug formation

Question 23

What is a plug?

Answer 23

A plug is a lightly compressed powder that can be used to fill a capsules. Plugs are prepared at much lower compression forces (20-30 N) compared to the forces used in tablets (30 kN)

Question 24

Why may potent drugs be easier to formulate?

Answer 24

The API would occupy <20% of the total volume

Flow properties will depend on the diluent used

• the diluent can be chosen to provide good flow properties and for plug-forming ability

Question 25

What is required for less potent drugs when being formulated for hard-shell capsules?

Answer 25

The properties of the drug will dictate the properties of the powder Excipients must be effective a low concentrations * limited amounts can be included in the formulation Flow properties can be improved using: * glidants to reduce friction with surfaces * lubricants to reduce adhesion

Question 26

List the 7 processes in filling capsules?

Answer 26

Question 27

What key points do you consider when doing a fill weight calculation?

Answer 27

Use a chart: Used to estimate how much of your powder will fit in a capsule. Choose a powder that is similar to your drug. Determine maximum capacity of the capsule Select a target weight at least 75% of the fill weight for the capsule Don't forget excipients

Question 28

When Does drug release begin for immediate release? A. Before the capsule has completey disintegrated B. After the capsule has completely disintegrated C. Until it reaches its target area

Answer 28

A. Drug release starts before the capsule has completely disintegrated/dissolved.

Question 29

Gelatin capsule take longer to to split than HPMC capsules for immediate release. TRUE or FALSE

Answer 29

FALSE HPMC capsules may take longer to split than gelatin capsules

Question 30

What diluents are preferred for Hydrophobic and Hydrophillic powders in immediate release? Give an example of each

Answer 30

**For an hydrophobic powder:** soluble diluents (e.g. lactose) should be preferred * Surfactants can also be added to improve the wetting of a hydrophobic powder **For an hydrophilic powder:** insoluble diluents (e.g. starch or microcrystalline cellulose) can be used

Question 31

What are the 7 steps the gelatin exterior splits upon dissolving in water?

Answer 31

Question 32

Formulation for immediate release diagram.

Answer 32

Question 33

What two ways are hard-shell capsules packaged?

Answer 33

Blister pack * can be opaque for added protection Glass/plastic bottle with a child-resistant cap +/- dessicant capsule

Question 34

What conditions must hard-shell capsules be stored in?

Answer 34

Cool and dry conditions

Question 35

What are the reasons for why a capsule might fail a uniformity test?

Answer 35

Question 36

How would you prevent leakages in the capsule?

Answer 36

Avoid aqueous liquid filling to maintain shell integrity Moisten the inside of the cap with hydroalcoholic solution Gelatin seal (industrial process) * gelatin "belt" around the capsule, sealing cap and body Use a suitable base for semi-solids * solid @ room temperature * liquid @ body temperature

Question 37

What is Over-encapsulation?

Answer 37

Filling a tablet in a capsule Filling a capsule in another capsule * Must ensure there and NO compatibility issues between the capsule and its contents

Question 38

Why would you over-encapsulate?

Answer 38

Mask the content of capsule Blind clinical trials

Question 39

How do you over-capsulate?

Answer 39

Whole or crushed tablet(s) Whole of emptied capsule(s) * consider the capsule size that will be required * consider which will have the least impact on the biopharmaceutical profile

Question 40

For Gelatin capsules, what factor is most liekly to have the most important impact on drug release?

Answer 40

Properties of content.

Question 41

Cross-linking of gelatin capsules can be detected during a disintegration test performed in the presence of pepsin? TRUE OR FALSE

Answer 41

FALSE

Question 42

Which strategy(s) canbe used to improve the dissolution rate of an encapsulated hydrophobic powder?

Answer 42

Soluble diluent