W22 Paediatric analgesic formulations (AM) Flashcards
What are Common paediatric dosage forms? (5)
- Suspensions
- Solutions
- Suppositories
- Orodispersible dosage forms
- Tablets/capsules may be suitable for older children
Suspensions:
Composed of?
Examples?
- Drug and/or other excipients **remain as solid particles ** dispersed in the aqueous “vehicle”
- Paracetamol (Calpol) and ibuprofen (Nurofen) are widely used in the UK
- Practice point: reinforce shake well/ KOORASOC
What is the definition of a solution?
Are they common paediatric dosage forms? why?
- Drug and other excipients are completely dissolved, i.e., as a molecular dispersion, in a liquid (solvent)
- Only paediatric solution available for treatment of mild to moderate pain is
Paediatric Paracetamol Elixir BP - Not recommended due to high ethanol content (8.4 % v/v)
Suppositories- definition?
Used for what?
Examples?
- Drug is incorporated into a water-soluble/dispersible base or a base which melts at body temperature
- Most commonly used for a local effect, but also used for the systemic delivery of paracetamol, diclofenac, indometacin and aspirin
- Paracetamol and diclofenac suppositories have uses in paediatric analgesia
- Paracetamol suppositories are available containing 60 mg, 125 mg, 250 mg, 500mg, and 500 mg of drug
- Useful if nausea and vomiting present
- Counsel parent/ guardian on how to use
What is the significance of Orodispersible dosage forms?
Different types? (4)
- Orodispersible dosage forms have been formulated to dissolve rapidly in the mouth so that the drug (+excipients) can be swallowed
- Orodispersible dosage forms can be classified as following:
1. Orodispersible tablets (including minitablets)
2. Oral lyophilisates
3. Orodispersible films
4. Orodispersible granules (not in UK) - They are distinct from sublingual and buccal formulations and other oromucosal preparations which are formulated to deliver drugs to the oral cavity/ throat or for a local or systemic effect
Orodispersible tablets can be prepared using which approaches? (3)
- Direct compression
- Sublimation
- Phase transition
Orodispersible tablets:
What ingredients are used in Direct compression?
- Manufacture is most commonly through
the direct compression process - Requires the incorporation of superdisintegrants, e.g. croscarmellose Na, crospovidone
Orodispersible tablets
What is Sublimation?
- Manufacture through sublimation involves the use of volatile solid substances, e.g. camphor, menthol, in the tablet mixture for
compression
*Sublimation of these ingredients leaves a porous tablet enabling easy penetration by fluid in the oral cavity
Orodispersible tablets
What is Phase transition?
- Phase transition method of manufacture – compression of a mixture of high/low melting point sugar alcohols, e.g. erythritol (122°C) and xylitol (93-95°C)
- Tablet heated to 95°C causing the xylitol to melt and diffuse leaving pores in the tablet. Unsuitable for heat sensitive drugs
Oral lyophilisates
- Oral lyophilisates are produced using a lyophilisation (freeze-drying) process
- Most widely-known technology is Zydis by RP Scherer (now Catalent)
- Dosage forms tend to be soft which means a different packaging process is required – more on this later
BP Definition of Oral Lyophilisates?
(for info)
Oral lyophilisates are solid single-dose preparations made by freeze drying of a liquid or semi-solid preparation. These fast-releasing preparations are intended to be placed in the mouth where their contents are released in saliva and swallowed, or alt are intended to be dissolved or dispersed in water before oral administration
Oral lyophilisates:
Why is lyophilisation used?
- Lyophilisation (freeze-drying) originally used in pharma to keep labile products stable
- 1980s: lyophilisates investigated as a dosage form
To understand freeze drying you need to understand phase diagrams
(Solid, Liquid, Gas, Triple point)
Temp on X, Pressure on Y axis
Oral lyophilisates – freeze drying
What are the 4 main stages?
(1) Freezing stage:
- This stage needs to be carefully controlled to obtain the desired ice crystals
- The packs are exposed to temperatures in the range -10 °C to -30 °C in large freeze drying units
- Liquid nitrogen used in this process
2) Vacuum application stage:
- Vacuum is applied to bring the pressure down below the triple point
* (3) Sublimation stage
- Heat of sublimation applied
- Sublimation of ice is a slow process
(primary drying)
- 0.5% moisture typically left after this
- Vapour continually removed
* (4) Secondary drying
- Residual moisture removed by raising
temp to 50 °C to 60 °C
Oral lyophilisilates: Zydis technology
What are the steps that this technology uses?
Foil blister forming
Blister filling with product mix
Tray cutting
Freezing (liquid nitrogen)
Lyophilisation (water removal)
Dried tablet trays removed for sealing
Blisters sealed, divided within primary packaging
Oral lyophilisates: clinical points
- Oral lyophylisates not currently used for paediatric (only) analgesia
- Many examples of commercially available products
E.g. − Rizatriptan – MAXALT MELT (migraine)
− Desmopressin acetate – DesmoMelt / DDAVP Melt / Noqdirna (polyuria /
polydipsia / nocturnal enuresis)
− Buprenorphine hydrochloride – Espranor (substitution in opioid dependence)
− Timothy grass pollen allergen – GRAZAX (immunotherapy – grass pollen induced
rhinitis and conjunctivitis)
− Ondansetron – Zofran Melt (nausea and vomiting)
− Many more..
