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 |
4 |
|
| Ethanol 95% |
10 |
mL |
| Parabens |
0.1 |
% |
| Syrup |
to 50 |
mL |
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| Ethanol is used to wet the powder. In the original study1 only 0.007% parabens was used; this concentration
is probably inadequate. |
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Expiry: 30 days. |
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Stability: reported to be chemically stable for at least six months but the assay
was not stability indicating. |
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Storage: Refrigerate. Protect from light. |
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SHAKE BEFORE USE |
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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
- 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.
- 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.
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