Formulation in Pharmacy Practice   2nd Edition

ONDANSETRON
 
 
Ondansetron hydrochloride dissolves in water and the pH of solutions is about 4.5 - 4.6.  A precipitate of free base develops if the pH is increased to 5.7 and above.1  The injection has a pH of 3.3 - 4.0.
Several stability studies have been performed on oral liquids prepared from crushed tablets or diluted injection.  In most cases, only a few doses of ondansetron are required with each course of treatment and tablet dispersion is a convenient option.

Tablet dispersion:
To disperse the tablet place in 10 - 15mL of water in a wide bottomed cup or glass.  Do not use a conical measure as the tablet tends to aggregate at the base.  Leave the tablet to disintegrate for about 10 minutes, swirling occasionally.  Eventually a cloudy suspension is formed which can be mixed with a flavoured cordial.  The mixture has a slight bitter aftertaste but is not too unpleasant to take without flavouring.

Formula A2

Ondansetron 4mg per 5mL
 
Ondansetron tablets   8mg 10   
*Vehicle as below to   100  mL
 
* Cherry Syrup USP, Syrpalta, Ora Sweet or Ora Sweet SF.
 
Expiry:  30 days.
 
Stability:   6 weeks at 4°C.
 
Storage:  Refrigerate.  Amber plastic bottles used in the study.
 
Shake well before use
 

 
Formula B3

Ondansetron 4mg per 5mL
 
Ondansetron tablets  4mg 20   
*Sodium Benzoate 0.2  %
Raspberry syrup BP to   100  mL
 
*Alternatively, use parabens 0.1%
 
Expiry/Stability:  14 days.
 
Storage:  2 - 30°C.
 
Shake well before use
 
NOTES
  1. Manufacturer reports that plain Syrup BP causes gross flocculation.  This is probably a pH effect causing precipitation of ondansetron.  Any syrup based vehicle can be used but to avoid precipitation ensure the pH is below about 4.5 by addition of citric acid.  N.B. precipitation may be difficult to detect due to presence of tablet excipients.
  2. Parabens 0.1% could be substituted for sodium benzoate.
  3. Raspberry Syrup BP is made as follows:
    Concentrated raspberry juice part
    Syrup 11  parts
    This should be freshly prepared.
 

 
Oral administration of the injection
Graham et al4 reported the stability of ondansetron hydrochloride oral liquids prepared by diluting the injection.  Solutions of approximately 0.27mg per mL and 0.07mg per mL in orange juice and cola were stable for at least 1 hour.  A solution of approximately 0.5mg per mL was stable for 7 days in cherry syrup (pH 3.4).

REFERENCES
  1. Leak RE, Woodford JD.  Pharmaceutical development of ondansetron injection.  Eur J Cancer Clin Oncol 1989; 25 (suppl 1): S67-S69.
  2. Williams CL, Sanders PL, Laizure SC, Stevens RC, Fox JL, Hak LF.  Stability of ondansetron hydrochloride in syrups compounded from tablets.  Am J Hosp Pharm 1994; 51: 806-8.
  3. Provided by the manufacturer of Zofran®.
  4. Graham CL, Dukes GE, Fox JL, Kao CF, Hak LJ.  Stability of ondansetron hydrochloride injection in extemporaneously prepared oral solutions.  Am J Hosp Pharm 1993; 50: 106-8.
 
 
     

 
Formulation in Pharmacy Practice
2nd Edition
© 2001 PharmInfoTech
ISBN 0-473-07577-6