Spironolactone is practically insoluble in water and soluble in alcohol. It is less stable in alkaline conditions with maximum stability at pH 4.5.1 Extemporaneously prepared spironolactone oral liquids, as described below, appear to be stable for at least 30 days and usually have a final pH in the range 3.5 - 6.5. Commercially manufactured spironolactone suspension is available in some countries.
The choice of formula will depend on the ingredients available and the acceptance of the excipients.
Formula E has not been formally studied but offers a convenient alternative method of preparation. This formula is based information in the literature and the published studies.
Some spironolactone suspensions have been observed to be excessively thick6 and care should be taken to observe the physical characteristics.
Formula A2
Spironolactone Solution 2.5mg per mL |
| |
| Spironolactone powder |
250 |
mg |
| Ethanol 96% |
20 |
mL |
| Propylene glycol |
10 |
mL |
| Glycerol |
to 100 |
mL |
| |
|
Expiry: 30 days. |
| |
Stability:
Chemically stable for 16 months at 4°C and 2 months at 19°C. |
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Storage:
The solution in this study was stored in screw-capped, glass amber vials. |
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Notes
- Microbial growth was not studied.
- Data from this study cannot be extrapolated to a liquid prepared using tablets instead of
powder.
- Ethanol content is relatively high.
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Formula B3
Spironolactone Suspension 25mg per mL |
| |
| Spironolactone tablets 25mg |
120 |
|
| *Vehicle |
to 120 |
mL |
| |
*Either:
1:1 mixture of Ora-Sweet and Ora-Plus,
1:1 mixture of Ora-Sweet SF and Ora-Plus,
or Cherry Syrup. |
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Expiry: 30 days. |
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Stability:
Chemically stable for 60 days. |
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Storage: 5°C or 25°C. Protect from light. |
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Shake well before use |
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Note
- The final pH for these oral liquids was in the range 3.7 - 4.4.
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Formula C4
Spironolactone Suspension 1mg per mL |
| |
| Spironolactone tablets 25mg |
10 |
|
| Carboxymethylcellulose 1.5% |
50 |
mL |
| Syrup |
100 |
mL |
| Water |
to 250 |
mL |
| |
|
Expiry: 30 days. |
| |
|
Stability:
Reported to be chemically stable for 3 months. |
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Storage: Room temperature. |
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Shake well before use |
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Formula D5
Spironolactone Solution 2mg per mL |
| |
| Spironolactone powder |
200 |
mg |
| *Parabens |
0.1 |
% |
| Ethanol |
10 |
mL |
| Syrup |
to 100 |
mL |
| |
Wet the powder with the ethanol and then mix thoroughly with simple syrup.
* Sodium benzoate 0.1% was used in the original study but this will not be active as a
preservative as the final pH was 6.2. Parabens is a suggested alternative.
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Expiry: 30 days. |
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Stability:
Reported to be chemically stable for 160 days. |
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Storage: Room temperature. Amber glass bottles used in the study. |
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Formula E
Spironolactone Suspension 1mg per mL |
| |
| Spironolactone tablets 25mg |
4 |
|
| Glycerol |
20 |
mL |
| Sodium Carboxymethylcellulose |
1 |
g |
| Parabens |
0.1 |
% |
| Water |
to 100 |
mL |
| |
|
Expiry: 30 days. |
| |
|
Storage: Refrigerate. Protect from light. |
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|
Shake well before use |
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Notes
- Final pH is about 6.4.
- Sodium carboxymethylcellulose can be replaced with methylcellulose 1%
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REFERENCES
- Pramar Y, Gupta VD. Preformulation studies of spironolactone: effect of pH, two buffer species, ionic strength, and temperature on stability. J Pharm Sci 1991; 90: 551-3.
- McKnight DL, Emmott, Sunderland VB, White S. Preliminary formulation and stability of a spironolactone oral solution for paediatric use. Aust J Hosp Pharm 1997; 27 (5): 390-394.
- Allen LV, Erickson MA. Stability of ketoconazole, metolazone, metronidazole, procainamide hydrochloride and spironolactone in extemporaneously compounded oral liquids. Am J Health-Syst Pharm
1996; 53: 2073-2078.
- Nahata MC, Morosco RS, Hipple TF. Stability of spironolactone in an extemporaneously prepared suspension at two temperatures. Ann Pharmacother 1993; 27: 1198-99.
- Gupta VD, Gibbs CW, Ghanekar AG. Stability of pediatric dose forms of ethacrynic acid, indomethacin, methyldopate hydrochloride, prednisone and spironolactone. Am J Hosp Pharm 1978; 35: 1382-85.
- Musgrove BS, Miwa LJ. Excessively thick extemporaneous spironolactone suspension [letter]. Am J Hosp Pharm 1989; 46 (3); 486.
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