Hard-shell Capsules Flashcards
What are the main two parts of a hard-shell capsule?
The cap-Shortest part of capsule
The body- Longest part of the capsule
How do hard-shell capsules prevent contents from being leaked out?
The contents are generally filled into the body before the cap is snapped into place.
What are the advantages of using capsules?
- They have longer shelf life than liquid dosage forms
- Simpiler formulation compared to tablets
- More convinient
- Tampering can be detected easily
- Good absorption profile
What re the two types of gelatin made for hard-shell capsules, and how are they produced?
- 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.
After the gelatin is hydrolysed, what is it isolated as?
After hydrolysis, gelatin is isolated as a light amber-faintly yellow vitreous (glass-like), brittle, odourless and tasteless solid.
What are the properties of fish gelatin?
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
What is bloom strength and what is its range in hard-shell capsule?
- 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.
How is viscoity measured with gelatin solution?
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.
Give 5 properties of gelatin capules?
- 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.
Which powders and APIs are incompatible with Gelatin capsules?
Hygroscopic powders, Deliquescent powders, Hydrolysis-prone APIs- API may absorb water from the shell which will affect both drug and capsule integrity.
What is Cross-linking?
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.
What factors cause cross-linking?
- aldehydes and ketones
- oxidising agents
- metal ions
- sugars
- heat
- high/low humidity
- light
What are the consequences of cross-linking?
- Low or incomplete cross-linking
- Delay in capsule disintegration
How may you go about addressing consequnces to do with cross-linking?
You can add protease to the dissolution medium;
Pepsin- mild to moderate cross-linking
Pancreatin- mild cross-linking
What is a sachet?
In terms of drug formulation, sachets will be used to deliver a small quantity of a medicine.
What can you put in a sachet?
Dry solids
- Powders
- Granules
Liquids
What are the advantages of using satchets for patients?
- Convinience
- Available as a unit dose
- Easy to prepare
- Easy to swalllow, compared to tablets/capsules
What are the advantages of satchets for pharmaceutical companies?
- 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
What are the advantages of using HPMC?
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
What is the main advantage of Pullalan use in hard-shell capsules?
Good barrier to oxygen
- Alternative for encapsulation of APIs sensitive to oxydation
Give the 4 unit processing involved in formulatiomn for encapulation.
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
What are the requirments for powder filling?
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
What is a plug?
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)
Why may potent drugs be easier to formulate?
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
What is required for less potent drugs when being formulated for hard-shell capsules?
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
List the 7 processes in filling capsules?
What key points do you consider when doing a fill weight calculation?
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
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
A. Drug release starts before the capsule has completely disintegrated/dissolved.
Gelatin capsule take longer to to split than HPMC capsules for immediate release.
TRUE or FALSE
FALSE
HPMC capsules may take longer to split than gelatin capsules
What diluents are preferred for Hydrophobic and Hydrophillic powders in immediate release?
Give an example of each
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
What are the 7 steps the gelatin exterior splits upon dissolving in water?
Formulation for immediate release diagram.
What two ways are hard-shell capsules packaged?
Blister pack
- can be opaque for added protection
Glass/plastic bottle with a child-resistant cap +/- dessicant capsule
What conditions must hard-shell capsules be stored in?
Cool and dry conditions
What are the reasons for why a capsule might fail a uniformity test?
How would you prevent leakages in the capsule?
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
What is Over-encapsulation?
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
Why would you over-encapsulate?
Mask the content of capsule
Blind clinical trials
How do you over-capsulate?
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
For Gelatin capsules, what factor is most liekly to have the most important impact on drug release?
Properties of content.
Cross-linking of gelatin capsules can be detected during a disintegration test performed in the presence of pepsin?
TRUE OR FALSE
FALSE
Which strategy(s) canbe used to improve the dissolution rate of an encapsulated hydrophobic powder?
Soluble diluent
