Theophylline versus aminophylline in rectal administration

Area of Science:

• Pharmacokinetics and Drug Delivery
• Pharmaceutical Formulation and Stability

Background:

• Rectal administration of theophylline is an alternative route for respiratory conditions.
• Suppositories offer controlled drug release, but formulation impacts bioavailability.
• Aminophylline, a salt of theophylline, has different solubility and release characteristics.

Purpose of the Study:

• To compare the bioavailability and in vitro release rates of theophylline from suppositories formulated with either theophylline or aminophylline.
• To evaluate the impact of formulation and storage on the rectal delivery of theophylline.

Main Methods:

• A blind, crossover study in six healthy volunteers compared the absorption of theophylline from solution and suppositories (theophylline or aminophylline).
• Serum theophylline levels were measured spectrophotometrically over 8 hours post-administration.
• In vitro release rates were assessed for freshly prepared and aged suppositories.

Main Results:

• Theophylline and aminophylline suppositories demonstrated near bioequivalence, with slightly higher Cmax for theophylline.
• In vitro release rates were significantly higher for freshly prepared aminophylline suppositories (4.8 mg/min) compared to theophylline suppositories (2.9 mg/min).
• Aminophylline suppositories showed a substantial decrease in release rate (4.8 to 0.5 mg/min) after 1-year storage.

Conclusions:

• Despite faster initial in vitro release, aminophylline suppositories exhibit poor stability, leading to reduced drug release over time.
• The bioequivalence of freshly prepared theophylline and aminophylline suppositories, coupled with aminophylline's instability, suggests that theophylline reformulations are preferable to ethylenediamine derivatives for rectal administration.
• Formulation choice significantly impacts the stability and release characteristics of rectal drug delivery systems.