Formulation in Pharmacy Practice  

CAPTOPRIL
 
Captopril is freely soluble in water, however aqueous solutions have a strong sulphur taste and would not be palatable.  Captopril is a thiol and undergoes oxidative degradation in aqueous solution.  The rate of degradation is dependent on pH and oxygen concentration.  Stability is decreased by contact with metal ions.  Antioxidants such as sodium ascorbate or ascorbic acid increase the stability of captopril in distilled water.  Maximum stability occurs below pH 4.

Captopril liquid (Capoten®) is commercially available in some countries and should be used whenever possible.  If captopril liquid is not available the tablets can be dispersed in water.  The drug is soluble so a volume that corresponds to the dose can be measured out and then given with a flavoured vehicle.  Low strength tablets or measured tablet fractions can be conveniently packed in oral syringes so that the water can be drawn up just before dose administration.

Several studies1-6 have been conducted to determine the stability of captopril oral liquid.  Lye et al1 have recommended the following formula:

Formula 1

Captopril 1mg per mL
 
Captopril tablets 25mg  
Simple syrup BP 25  mL
 
Expiry:  30 days
 
Storage:  Refrigerate.  Protect from light.
 
Shake well before use
 

 
NOTES
  1. This study found that the liquid formulated from captopril tablets was more stable than that made from captopril powder.  This is in contrast to previous studies.2,3
  2. A study was conducted by Nahata et al4 using three different vehicles (100mL syrup or 100mL water or 100mL water plus 500mg sodium ascorbate).  The syrup formulation was the least stable due to the trapped air particles increasing the rate of oxidation.  The water/sodium ascorbate vehicle was the most stable (56 days at 4°C) due to the decreased oxidation.  The microbial stability could not be assured up to 56 days.
    Ascorbic acid can be used instead of using sodium ascorbate without compromising stability.  If ascorbic acid powder is unavailable use plain tablets rather than effervescent.
  3. Other studies5,6 have produced highly variable results depending on the quality of water used.

REFERENCES
  1. Lye M, Yow K, Lee L, Chan S, Chan E, Ho P.  Effects of ingredients of stability of captopril in extemporaneously prepared oral liquids.  Am J Health-Syst Pharm 1997; 57: 2483-2487.
  2. Premar Y, Das Gupta V, Bethea C.  Stability of captopril in some aqueous systems.
    J Clin Pharm Ther 1992; 17: 185-189.
  3. Chan DS, Sato AK, Claybaugh JR.  Degradation of captopril in solution compounded from tablets and standard powder.  Am J Hosp Pharm 1994; 51: 2105-2107.
  4. Nahata MC, Morosco RS, Hipple TF.  Stability of captopril in liquid containing ascorbic acid or sodium ascorbate.  Am J Hosp Pharm 1994; 51: 95-6.
  5. Pereira CM, Tam YK, Stability of captopril in tap water.  Am J Hosp Pharm 1992; 49: 612-615.
  6. Anaizi N, Swenson C.  Instability of aqueous captopril solutions.  Am J Hosp Pharm 1993; 50: 486-8.

 
Formulation in Pharmacy Practice
2nd Edition