Week 11 - Oral Solid Dosage Forms and Packaging of Oral Solids Flashcards
Why do we coat formulations
- Make it easier to swallow
- use polymer coat that swells into gel when in contact with H2O
- gel makes tablet slippery = easy to swallow - Ensure dissolution happens in specific location
- can dissolve a specific pH, target specific location in gut, release in small intestine etc. - Ensure drug is released a certain way
- Improve chemical stability
- physical barrier to light + humidity - Mask unpleasant taste = ↑ adherence / compliance
- coating inhibits drug from dissolving in mouth - Mask appearance of drug core
- coat can be opaque
- if drug colour is diff. patients may not take medication - Identification of medication
- apply a coat with a dye or pigment - Keep manufacturing staff safe when handling
- e.g. highly potent drugs for cancer
List the different coating processes
- Sugar coating
- Film coating
- Compression coating
Explain how Sugar Coating works (Process 1)
Less common in medicine
- Use coating solution = has additional drying (~ wet manufacturing)
- 2 types of sugar coating
- After coating tablets can be used or undergo printing + lettering step (identification)
Process 1:
1. Tablet cores are surrounded / coated with a thick layer of amorphous solid sugar in a coating pan
- apply multiple layers of sugar syrup = thick coating
2. Tablet cores are rotated in pan
= tablets move over each + syrup gets transferred + spread over the cores + smoothed out
- spreading causes coat to get thinner + dry quicker
3. Tablets in zone 2 + 3 move over each other very fast BUT tablets in zone 1 (dead zone) = problem
- tablets in zone 1 have little movement + only come in contact with same particles = ↓ spreading
Avoid dead zone by reducing load of tablets, ↑ rotation speed, installing baffles
Explain how Sugar Coating works (Process 2)
Less common in medicine
- Use coating solution = has additional drying (~ wet manufacturing)
- 2 types of sugar coating
- After coating tablets can be used or undergo printing + lettering step (identification)
Process 2:
1. Seal the dry tablet cores to protect them from moisture
- seal with 4-8 layers of sugar syrup
2. Layers are dried quickly with warm air + drying powder mixture
3. After sealing real sugar coat is applied (uncoloured syrup)
- subcoat has up to 40 layers
- use coating suspensions to ↓ amount of layer = quickens process
4. Smooth the rough surface of sugar coat out
- by diluting coating syrup with sugar syrup
5. After subcoat add coloured coat
- gives tablets final appearance
6. Polishing step (thin wax layer to create shine)
- wax / fat can be dissolved in solvent + applied like syrup (solvent evaporates = shine left behind)
- put solid wax in tablet bed OR thin wax layer in coating pan
- tablets rolling over each other smooth surface out
What excipients are used in Sugar Coating
Process 2:
- Dry mixing powder e.g. starch, fumed silica, calcium carbonate, talc
- Sugar syrup can contain plasticiser, gelatine
- Use coating suspensions to ↓ amount of layer required = quickens process
- BUT they dry slower than thin layers of syrup = PROBLEMS (like tablet cores sticking together) - Coloured coat = coating syrup + 15% colouring agent
- use insoluble pigment = ↑ opacity
Explain how Film Coating works
Most common
- Use coating solution = has additional drying (~ wet manufacturing)
Generation of a thin film of polymer coating around the tablet core
- film can dissolve or swell (depending on polymer used)
- film is thin = doesn’t affect appearance of tablet
PROCESS
(same as sugar coating BUT generate THIN layer)
1. Tablet cores in coating pan
2. Apply coating syrup / polymer over it
3. Rotate pan allowing tablets to move around
What excipients are used in Film Coating
- Polymers
- cellulose esters e.g. CAP (swell in contact with water = gel)
- acrylate polymers (water soluble = swell)
- PVP - Plasticisers
- e.g. polythene glycol, glycerol, organic esters and oils - Solvents
- water or organic solvent e.g. methanol, acetone, water+ethanol
- solvent dissolves polymers so it can be applied in coating step
- coating needs to be done in well aired environment with explosion protection when using methanol / acetone
- water + ethanol = safer + less risk of solvent residue in medicine (= toxic side effects) - Colourants
- insoluble pigment (e.g. iron oxide, titanium oxide)
- water soluble dyes (e.g. sunset yellow) - Opaquant extenders
- make films more opaque (less transparent) + increase film coverage
- e.g. titanium oxide, talc, magnesium carbonate
Explain how Compression Coating works
Generate a layer around tablet core by compressing granulated material onto it
- can generate IR, SR or 2 diff. MR (core + shell) combined
What excipients are used in Compression Coating
Refer to Tableting flashcards
What are the critical core properties for coating
- Hardness (no less than 80N)
- tablets have to roll over each other without breaking - Friability (0.1% to 0.5%)
- tablets undergo stress during tumbling motion in pan = can crack / chip - Tablet Porosity
- ↑ porosity = ↓ tablet hardness
- porosity affects adhesion of film to the core - API (in core)
- can affect adhesion of film to core - Lubricant (excipient)
- ↓ tablet hardness and ↓ adhesion of film - Disintegrants
- remove moisture from film before it properly forms = orange peel effect
FILM COATING
Core dimensions don’t matter, can also be used for flat faces
SUGAR COATING:
Tablet core needs to have specific dimensions to allow them to roll over each other + not aggregate
- flat faces are not coatable (tablets will stick)
- radius of face needs to be 0.7-0.75
- height of sides needs to be between 7-13% of table diameter (S)
- if S is too low = fragile sides = fracture in pan
- if S is too high = excess coating = likely to fracture + detach from core
Dimension help calculate the amount of coating sugar syrup need to prepare
Why do we need packaging
- identification of medicine
- protect medicine from degradation
- convenience
- compliance
- provide info. related to medicine
What are the regulations for packaging
HMR Act 2012 - OUTER packaging
- brand name and common name of API
- strength, dose, formulation, route of administration, directions, storage requirements
- expiry date, name + address of marketing authorisation, batch no.
- statement - if its suitable for children, for oral use only etc.
- all excipients listed (if injectable medicine)
HMR Act 2012- BLISTER packs
- brand name, common name of API, strength, formulation
- if suitable for children
- expiry date, name of marketing authorisation, batch no.
Primary packaging - in direct contact with medicine
Secondary packaging - only in contact with primary packaging + PIL
- outer packaging e.g. box
Explain the packaging process (blister packs)
- Foil is rolled between 2 heated rollers + begins to soften
- 1 roller is flat + 1 has moulds (to create blister shape) - Foil is pulled into mould (by vacuums)
- foil forms blister shapes - Capsules flow through hopper + enter the blisters in foil
- Close blister with backing foil (aluminium)
- Foil is stamped with required info
List the materials needed to form blister packs (packaging)
- Plastics
- e.g. PVC or PET to make blister foils
Excipients they may contain:
- plasticiser, fillers, lubricants, catalysts, colourants etc.
- anti oxidants, UV blockers,
- PVC can have UV blockers, antioxidants, stabilisers
- PROBLEM = excipients may leech into polymer / medicine - Metals
- Aluminium to close blister packs
- used ONLY in packaging go non-parenteral (everything but IV/IM)
Describe PET and PVC Plastics
Packaging requires extensive polymerisation to make a solid polymer (many monomers joint = macromolecules)
2 classifications for plastics
Thermoplast = mouldable when heated
Thermoset = not mouldable when heated
Types of Plastics:
1. PET - Polyethylene Terephthalate
- a thermoplast polymer (a polyester)
- is a STABLE, partially crystalline material (strong intermolecular interactions)
- HAS ↓ vapour + ↓ gas permeability = ↓ risk of oxidation
- is transparent, harmless to patient
- formed from terephthalic acid and ethylene glycol + catalyst (antimony oxide = toxic to bones + teeth = want NO residue in drug)
- has catalyst does NOT require plasticiser
- PVC - Polyvinylchloride
- a thermoplast polymer
- HAS ↓ vapour + ↓ gas permeability = ↓ risk of oxidation
- has LOW STABILITY when warmed in light (photolysis) + in presence of O2 (oxidation) = degrade
- is resistant to many chemicals
- its hard + brittle in its pure form = needs to be polymerised
- PVC-U (pure, unplasticed) form is used in foils
3 Ways polymerisation of PVC occurs
1. EMULSION polymerisation in water
- initiator used is water soluble = is washed out = good
2. Suspension polymerisation in water
- initiator used is soluble in monomer = stays in polymer = bad
3. Water free polymerisation
- initiator is soluble in monomer = stays in polymer = bad
