Satchets and powder capsules Flashcards
What is a satchet? what is it used for?
- used to deliver a small quantity of a medicine
- immediate release
- used to administer
- > dry solids; powders and granules
- > liquids
advantages and disadvantages of satchet use?
Advantages > convenience and easy > available as unit dose > easy to prepare > easy to swallow
Disadvantages
> relative use of manufacture
> increased shelf-life
> variable dose easily made by adjusting filled volume
> cost benefits; potentially less costly to ship compared to liquid dosage forms
What are the type of excipients that can be used and give some examples of these
Filler- dextrose, mannitol Glidant- silicon dioxide Sweetener- mannitol, marital Binder- starch Encapsulation- cyclodextrius
what contains the fewest excipients and why?
capsules contain fewest excipients as organoleptic properties is less worry for any other dosage forms presented
how can you achieve controlled release satchet formulation
requires the use of granules which can be coated with a gastro-resistant or modified-release coating
How can you see if a powder filing has passable flow?
corresponds to a Carr’s index of <25%
What is the particle settling time? How long should this be and what should be avoided?
relates to how quickly the powder settles at the bottom of the sachets
this time should be 1s max and the aeration of particles should be avoided
Explain the Wall Friction angle
it is the friction angle between bulk powder and a solid surface
what is mass flow? what does it decrease the risk of?
mass flow, the bulk powder moves as one, decreasing the risk of particles getting separated depending on size
What should the wall friction angle be for speedy satchet production?
<20 degrees
Particles that have funnel flow pattern, what can occur
demixing can happen as large and small particles have different flowabilities
- affects powders homogeneity
What is the Kawakita 1/b parameter?
relates to how much the bulk volume changes under an applied force
-> additional method to assess powder flow; for satchets it should be >5MPas
why are laminates used in packaging satchets?
to maximise shelf-life
What properties should good satchet packaging have?
- good moisture and chemical resistance
- paper/plastic based
- easily sealable; avoid loss of powder
- high mechanical performance; for transport and storage
- easy to use and safe; child-resistant packaging
what type of capsules can you have?
hard shell and soft shell
What do hard shell capsules look like and consist of?
- cylindrical in shape
- have to main parts:
- > body; longest part
- > cap; shortest part
body and cap are snapped in place to prevent leakage
what are the advantages of hard shell capsules?
what’s a disadvantage of large capsules?
- > simplicity of formulation
- > convenience
- > good absorption profile
- > tampering can be easily detected
some can find it difficult to swallow
What are hard shell capsules usually made of and how is it produced?
gelatine
it is produced through hydrolysis of collagen; protein is found in connective tissue and treated under acidic/alkaline conditions to generate gelatine
What are the different types of gelatine?
Type A: produced through acid hydrolysis; pH1-3
Type B: produced through basic hydrolysis; 3 month process
What are advantages about using fish gelatine?
- odourless
- tasteless
- renewable source
- collagen can be extracted from fish bones and skin
What is the bloom strength of gelatine? explain this characteristic
it typically has a bloom strength ca. 230-275g
bloom strength allows us to see the rigidity of gelatine gel and corresponds to ‘the force needed to depress the surface of a gelatine gel by 4mm, using a 12.7mm diameter flat-bottomed plunger
What are other characteristics of gelatine?
- good mechanical properties
- readily dissolved in water at body temp; swells and softens
- have moisture content; 13-16%
- > water acts as a plasticiser
How do capsules react in high and low humidity environments?
- they will absorb water in high humidity; shell is softer and so malleable
- they will release water in low humidity ; shell is brittle and prone to breakage
What powders are incompatible?
- hygroscopic powders
- deliquescent powders
- hydrolysis-prone APIs; API may absorb water from the shell which affect drug and capsule integrity
What does cross-linking of capsules do?
alteration of gelatine performance which slows shell disintegration and releases formulation slower
- covalent bonds between chains form and is irreversible
What is the causation for cross linking?
- aldehydes and ketones
- oxidising agents
- metal ions
- heat
- light
- low/high humidity
Consequences of cross-linking of capsules?
low/incomplete dissolution of capsule
- delay in capsule disintegration
- > cross linking effect can be addressed by adding proteases to dissolution medium
What ingredients can shell formulation include?
Colouring sugars
-> water-soluble drugs
-> water-insoluble pigments
Opacifying agents
-> added to make shell opaque for light protection
Processing aids
-> surfactants can be added as wetting agents
-> allows uniform coverage of moulds when manufacturing the empty capsule
shells
What can be used to prevent contamination
preservatives
- accepted that water content is insufficient and too tightly bound; prevents microbial growth
What characteristics make potato starch a good alternative material for hard shell capsules?
- it is a plant source
- has a low moisture content of 12-14% and moisture is tightly bound
- capsules can be coated; good adhesion and use for MR preparations
- capsules tend to be opaque
- odourless and tasteless
- similar dissolution profile to gelatine
- sealed by applying an hydro-alcoholic solution the inside of the cap
What characteristics make HPMC a good alternative material for hard shell capsules?
- gels at high temps
- stays soluble at lower temp
- plant source and good stability
- has low MC of 2-6%; less hygroscopic than gelatine capsules and less sensitive to low moisture environments
- less risk of moisture being transferred from shell to content
- few incompatibility issues vs gelatine
What characteristics make potato starch a good alternative material for hard shell capsules?
- plant source
- disintegration and dissolution similar to gelatine
- can produce capsules with transparent shells
- MC of 10-15%
- good barrier to O2
- capsules may adhere to tongue, palate, throat or oesophagus
What disadvantages does HPMC have for use as hard-shell capsule material?
- not best choice for encapsulation of drugs/excipients sensitive to oxidation
- production process varies with manufacturers
- > leads to different release profiles
- > some manufacturers use gelling agents which slow disintegration/dissolution of capsule
What sizes of hard shell capsules can you obtain?
variety from 000 to 5
- most human use will size from 0-4
elongated capsules are also available that provide 10% extra fill volume
what does capsule size selection depend on?
- the formulation
- > the capsule needs to be able to accommodate the whole of powder required for dose - the patients
- > small capsules with colours are preferred
Name the steps for powder formulation for encapsulation
- Particle size reduction; ensure homogenous mixing and decrease demixing risk
- mixing; as required
- filling of capsules
- packaging of product
What requirements are need for a powder filling?
- capsules are filled uniformly
- final product is stable
- drug is released and available for absorption within expected time frame
- final product complies with pharmacopoeial quality requirements
needs good flow properties
- adhesion avoided
- cohesion may be desirable for plug formation
Define a plug formulation
a plug is a lightly compressed powder that can be used to fill a capsule. Plugs prepared at much lower compression forces (20-30N) compared to the forces used in tablets (30kN)
why may potent drugs may be easier?
- API would occupy <20% of the total volume
- flow properties will depend on the diluent used
What properties will have less potent drugs have? How can flow properties be improved?
- properties of drug will dictate powder properties
- excipients must be effective at low concentrations
- flow properties can be improved using:
- > glints to reduce friction with surfaces
- > lubricants to reduce adhesion
What tests do pharmaceutical capsules need to comply with?
- Uniformity of dosage form
- uniformity of content (test B) if API <2mg or <2% of the fill mass; otherwise only need to comply with uniformity of weight test - disintegration test
- performed in water +/- 0.1M Hal +/- enzymes
- 30 min; valid for gelatin - dissolution testing
- similar requirements to tablets
How should hard shell capsules be packaged and stored?
Packaging
- > blister pack; can be opaqued for extra protection
- > glass/plastic bottle with a child resistant cap +/- desiccant capsule
Storage
-> cool and dry place
What is over-encapsulation? Why and how is it done?
- filling a tablet in a capsule
- filling a capsule in another capsule; must be no incompatibility with capsule and contents
- masks the capsule content and used in blind clinical trials
- done by using whole or crushed tablets and whole of emptied capsules
- > consider capsule size required
- > consider which will have the least impact on the biopharmaceutical profile
How is liquid and semi-solid filling done for hard-shell capsule? how is leakage prevented?
it is manually filled by weight or volume
- avoid aqueous liquid filling to maintain shell integrity
- moisten cap inside with hydro alcoholic solution
- gelatin seal (industrial process)
- use a suitable base for semi-solids
name some long and medium chain triglycerides that can be used for liquid/solid filled hard-shell capsules
long
- maize oil
- olive oil
- soybean oil
medium
- miglyol 810
- miglyol 812
Why is controlled release formulation used for hard shell capsule
- it protects active substances from harsh environment
- improve tolerability
- can control where the drug is released in the GI tract
Why is immediate release formulation used for hard shell capsules? what can its benefits be?
- capsules disintegrate at body temp quickly
- drug release starts before capsule has completely disintegrated/dissolved
- HPMC capsules take longer to split than gelatine capsules
- powder content properties impact release rates
What kind of diluents must be used for hydrophobic and hydrophilic powders?
For hydrophobic powder you should use a soluble diluent; surfactants can also be added to improve the wetting of a hydrophobic powder
e.g. lactose
For a hydrophilic powder you should use an insoluble diluent to provide additional control over the release rate
e.g starch or microcrystalline cellulose
How should fill weight calculations be done step by step?
- Use a chart
- charts provide information of the fill weight for common drugs/chemicals. can estimate how much of your powder will fit into a given size capsule and so what size to use. - Calculate the quantities, whether or not you know the densities of your API and excipient(s)
How do you use a chart to calculate fill weight?
- choose a powder from the chart that is similar to the drug
- determine the max capacity of the capsule
- select a target weight at least 75% of the fill weight for the capsule
- don’t forget excipients?
How does the dosator-type system work?
- a cylinder is lowered into the powder
- the powder is forced up the cylinder to form a plug
- the plug is released into the capsule shell
Name the main steps that are involved in the manual production of capsules
- separate the caps from the capsule bodies
- place the bodies in the filling machine
- uniformly fill the bodies to capacity
- replace the caps
- lock the caps into place or seal the capsules; sometimes the capsules can be sealed with a gelatin band or hydro alcoholic solution
- clean and polish the capsules
how can capsules be filled?
individually or using a manual capsule filler
What type of systems and machines can be used in industrial-scale capsule production?
the auger filling system and other systems can use the capsule body to measure the powder
systems like the dosator system uses a dosing tube to measure the required amount of powder, forming a plug in the process
