Lecture 9: Capsules Flashcards
Define capsule
An edible package made from gelatin or other suitable material which is filled with medicines to produce a unit dosage, mainly for oral use
Why are capsules often used in preclinical and clinical phases of drug development?
You dont need to develop a formulation to make a tablet
Usually just fill the capsule with the API
Maybe apply enteric coating if you want sustained release
Easy to produce placebo capsules
What are the advantages of capsules?
- Accurate dosage
- Easier to formulate/produce than tablets
- Capsule shells are smooth and easier to swallow than tablets
- Capsule shell eliminates contact between the drug and the mouth —> masking of taste and odorless
- Capsules can be attractively colored and printed on —> good appearance
- For patients who have trouble swallowing (e.g. pediatric and geriatric patients), capsule can be opened up and the contents mixed with food
What are the disadvantages of capsules?
- More costly to manufacture (vs tablets)
- Larger in volume than tablets –> more storage space
- Hygroscopic materials may dry out the capsule shell and cause it to become brittle
- Capsule shell typically contains 13% - 16% water
- Capsule shell can absorb moisture from the environment and/or content —> bloated
- Capsule-filling machine can be more complex than tableting press
What are the types of capsules?
- Hard capsule: two pieces that fit into each other, can contain dry fills, liquids & semisolids
- Soft capsule: Can contain liquids, and semisolids, commonly used for poorly water-soluble drugs in liquid formulatio
What are the common excipients needed in capsules?
Film former
Colorants
Wetting agents
Preservatives
Plasticizers
Excipients covered in Tablet I and II (note: what types of excipient are less relevant for
capsules???)
For liquid/semisolid-filled hard capsule: Oil / fatty acid, Surfactant, Cosolvent
What are the types of gelatin and how are they prepared?
- Type A gelatin: more plastic and greater clarity than type B
produced by acidic hydrolysis of mainly animal bones - Type B gelatin: Forms tougher films and is a little hazier than type A, produced by basic hydrolysis of mainly animal (bovine) bones
Explain the process of acidic hydrolysis to obtain type A gelatin.
- Animal skin is washed in cold water
- Digested in dilute mineral acid like h2so4 or h3po4 or hcl until maximum swelling (takes ~24 hrs)
- Wash swollen stock with water to remove acid
- Adjust pH to 3.5-4.0
- Hot water extraction to obtain gelatin (increase temp until you get the max yield)
- Solution is cooled for form jelled sheets which are dried in oven
- Ground gelatin to the desired particle size
Explain the process of basic hydrolysis to obtain type B gelatin.
- Animal bones decalicified by washing in acid to obtain ossein
- Ossien is held in a calcium hydroxide (lime) slurry for a period of 1–3 months at 15–20 °C.
- Wash with cold water to remove lime
- Neutralise stock with acid (HCL< h2so4, h3po4)
- Hot water extraction to obtain gelatin (increase temp until you get the max yield)
- Solution is cooled for form jelled sheets which are dried in oven
- Ground gelatin to the desired particle size
Is gelatin soluble in water?
It is soluble in hot water (above 40deg)
What is bloom strength?
- A measure of gel rigidity
- Determined by preparing a standard gel (6.66% w/w) and maturing it at 10°C — > the load in grams required to push a standard plunger 4 mm into the gel.
- A cylinder probe typically of 12.7 mm diameter is lowered into the gel system at a fixed speed.
What is the typical bloom strength of gelatin capsules?
200-250 g for hard capsules
150 g for soft capsule
What is the unit of bloom strength?
grams
What are the advantages of using gelatin for capsule shells?
- It is non-toxic, widely used in foodstuffs, and acceptable for use worldwide.
- It is readily soluble in biological fluids at body temperature.
- It is a good film-forming material, producing a strong flexible film. The wall thickness of a hard gelatin capsule is about 100 μm.
- Solutions of high concentration, 40% w/v, are mobile at 50°C. Other biological polymers, such as agar, are not.
- A solution in water or in a water-plasticizer blend undergoes a reversible change from a solution to a gel at temperatures only a few degrees above ambient.
What are the disadvantages of using gelatin for capsule shells?
- It is an animal protein — > characteristic variation, animal diseases & religious
considerations - It is moisture sensitive –> Can absorb moisture from the environment and from the drug formulation OR It may absorb and react with other components of the drug formulation.
- Its properties may change with adsorbed constituents
What is the disease that gelatin consumption could cause, and how should we prevent it?
Bovine spongiform encephalopathy
The prion that causes this may be carried over, even after the harsh treatment needed to make gelatin
Gelatin must be obtained from certified BSE-free production areas –> only healthy animals
Gelatin must not contain animal parts exposed to neurological tissues such as the skull and backbone vertebrae
What are examples of non gelatin polymers that can be used in capsules?
- Hydroxypropyl methylcellulose (HPMC)
- Pululan
What is one disadvantage of HPMC over gelatin and how can we solve it?
HPMC forms a gel at higher temperature, which means that more expensive equipment is needed to make the gel
Gelling agents like kappa-carrageenan and gellan gum can be added to form the gel
How does kappa carrageenan and gellan gum work to help HPMC to gel at a lower temp?
They form helical structures at room temperature, so gelation occurs via interactions between the helixes
Where does pullulan come from
A. pulllulans fungus
Pullulan is synthesised in the cell and its secreted out of the cell to form a protective layer for the fungus
