| 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
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.
- 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.
- 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.