Formulation in Pharmacy Practice   2nd Edition

AMINOPHYLLINE
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Aminophylline is a stable mixture of theophylline and ethylenediamine; the ethylenediamine confers greater solubility in water.  Aminophylline is a weak base (pKa of 5.0).  It is freely soluble in water but if the pH falls below 8 theophylline can precipitate.

Oral solutions of theophylline and aminophylline are available in some countries.  The USP solution of aminophylline has a pH of 8.5 - 9.7.  If available the commercial solution should be used.

Aminophylline injection has a pH of 8.6 - 9.0.  The injection, 25mg per mL, could be given orally but significant errors can occur in measuring small volumes of concentrated drugs.  For oral administration to infants dilution of the injection is recommended.

Nahata et al1 reported the stability of aminophylline solution 5mg per mL prepared by diluting the injection (Abbott Laboratories) with bacteriostatic water for injection containing 0.9% benzyl alcohol.  Solutions were chemically stable for at least 90 days at 4°C and 22°C packed in plastic syringes.  Bateriostatic water for injections is not available in many countries and many paediatricians would consider the use of even small amounts of benzyl alcohol undesirable.  The injection can be diluted with plain water for injections and packed aseptically into plastic oral syringes.  Solutions should be chemically stable for at least 30 days, but the expiry date assigned will depend on microbiological validation of the process.  These solutions should be refrigerated.  The solutions should be protected from light and packed in airtight containers.  Exposure to air can cause the breakdown of theophylline/ethylenediamine complex causing a cloudy appearance.  The effect of diluting other brands of aminophylline injection may need validation.  All diluted aminophylline preparations should be periodically checked for signs of precipitation.

Chong et al2 evaluated the stability of 3mg/mL and 21mg/mL oral liquids prepared by diluting the commercially available injection (25mg/mL) in a 1:1 mixture of Ora Sweet:Ora Plus.  The 3mg/mL liquid was chemically and physically stable for up to 90 days at 4 and 25°C.  The 21mg/mL liquid was also stable for 90 days at 25°C but failed to maintain 90% of initial concentration when stored at 4°C.

REFERENCES
  1. Nahata M.C., Morosco R.S., Hipple T.F.  Stability of aminophylline in bacteriostatic water for injection stored in plastic syringes at two temperatures.  Am J Hosp Pharm 1992; 49: 2962-3.
  2. Chong E., Dumont R.J., Hamilton D.P., Koke P.M., Ensom MHH.  Stability of aminophylline in extemporaneously-prepared oral suspensions. 
     J Inform Pharmacother 2000; 2: 100-6. 

 
Formulation in Pharmacy Practice
Page Updated August 2011