Formulation in Pharmacy Practice   - eMixt

Spironolactone
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Properties
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 appear to be stable for at least 30 days and usually have a final pH in the range 3.5 - 6.5.

Spironolactone has an unpleasant, bitter taste which can be difficult to mask. Compounded suspensions are often very susceptible to sedimentation and caking and may be difficult to re-suspend, leading to erratic dosing. 

 

 Alternatives to compounding
Commercially manufactured spironolactone suspension is available in some countries and should be obtained whenever possible.
Important note for New Zealand
A funded oral liquid is available and should always be used instead of compounding.

 

Compounded formulations
The choice of formula will depend on the ingredients available and the acceptance of the excipients.
Formula D 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 thick5 and care should be taken to observe the physical characteristics.



Formula A2

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.
Expiry:  30 days.
Stability:   Chemically stable for 60 days.
Storage:  5°C or 25°C.  Protect from light.
Shake well before use
Note
  1. The final pH for these oral liquids was in the range 3.7 - 4.4.

 

Formula B3

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.
 
Storage:  Room temperature.
 
Shake well before use
 

 
Formula C4

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.
Expiry:  30 days.
Stability:   Reported to be chemically stable for 160 days.
Storage:  Room temperature.  Amber glass bottles used in the study.
 

 

Formula D

Spironolactone Suspension 1mg per mL
 
Spironolactone tablets  25mg
Glycerol 20  mL
Sodium Carboxymethylcellulose g
Parabens 0.1  %
Water to   100  mL
Expiry:  30 days.
Storage:  Refrigerate.  Protect from light.
Shake well before use
Notes
  1. Final pH is about 6.4.
  2. Sodium carboxymethylcellulose can be replaced with methylcellulose 1%

 

References
  1. 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
  2. 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.
  3. Nahata MC, Morosco RS, Hipple TF.  Stability of spironolactone in an extemporaneously prepared suspension at two temperatures.  Ann Pharmacother 1993; 27: 1198-99.
  4. 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.
  5. Musgrove BS, Miwa LJ.  Excessively thick extemporaneous spironolactone suspension [letter].  Am J Hosp Pharm 1989; 46 (3); 486.

 
Formulation in Pharmacy Practice - eMixt
Page updated July 2014