Formulation in Pharmacy Practice   2nd Edition

INDOMETHACIN
 
Indomethacin is practically insoluble in water and sparingly soluble in alcohol.

For optimum stability an acidic pH of 4 - 5 is required together with the inclusion of co-solvents such as ethanol and glycerol.  Acidic suspensions without co-solvents are relatively unstable.  Indomethacin preparations are light sensitive.  Indocin® oral suspension may contain sodium hydroxide or hydrochloric acid to adjust the pH to 4 - 5.

Formula 1

Indomethacin 2mg per mL
 
Indomethacin capsules 25mg
Ethanol 95% 10  mL
Parabens 0.1  %
Syrup to   50  mL
 
Ethanol is used to wet the powder.  In the original study1 only 0.007% parabens was used;  this concentration is probably inadequate.
 
Expiry:  30 days.
 
Stability:  reported to be chemically stable for at least six months but the assay was not stability indicating.
 
Storage:  Refrigerate.  Protect from light.
 
SHAKE BEFORE USE
 

Other Formulations 2

A number of formulations prepared from Indomethacin powder were investigated including one similar to that described above.
  • 2mg per mL
    Indomethacin 200mg, raspberry syrup 20mL, glycerol to 100mL.  This formulation was difficult to re-disperse but showed excellent dose uniformity when dispersed.  Chemically stable for at least 30 days under refrigeration.
    Suspensions prepared from capsules may have a different pH due to capsule excipients.  Check that the pH is the range 4 - 5.

Preservative and alcohol free preparation
If such a preparation is required for an infant, a simple dispersion of the capsule contents in a mixture of 20% glycerol and sterile water is suggested.  Prepare a fresh supply every 48 hours, refrigerate, protect from light and ensure complete re-dispersion before administration.

REFERENCES
  1. Das Gupta V., Gibbs C.W., Ghanekar A.G.  Stability of pediatric liquid dosage forms of ethacrynic acid, indomethacin, methyldopate hydrochloride, prednisone and spironolactone.  Am J Hosp Pharm 1978; 35: 1382-85.
  2. Stewart P.J., Doherty P.G., Bostock J.M., Petrie A.F.  The stability of extemporaneously prepared paediatric formulations of indomethacin.  Aust J Hosp Pharm 1985; 15 (1): 55-60.

 
Formulation in Pharmacy Practice
2nd Edition