Bioavailability of sustained-release theophylline formulations

Area of Science:

• Pharmacology
• Drug Delivery Systems

Background:

• Sustained-release drug formulations aim for prolonged and constant active principle release in the gastrointestinal tract.
• This leads to more extended blood level curves for various medications, including theophylline.

Purpose of the Study:

• To assess the bioavailability of two sustained-release microencapsulated theophylline formulations and one sustained-release Diffucaps formulation.
• To compare these formulations against an equivalent dose of theophylline solution.

Main Methods:

• Bioavailability assessment of three sustained-release theophylline formulations.
• Comparison with a theophylline solution as a reference.
• Estimation of steady-state blood levels from single-dose study data.
• Evaluation of time duration above 75% of maximum steady-state theophylline plasma levels with a 12-hour dosing interval.

Main Results:

• None of the tested sustained-release formulations showed significant differences in bioavailability compared to the theophylline solution.
• All three sustained-release formulations demonstrated favorable peak and trough blood levels after prolonged administration.
• The sustained-release microencapsulated formulations maintained theophylline plasma levels above 75% of the maximum steady-state for 100% of the 12-hour dosing interval.

Conclusions:

• Sustained-release theophylline formulations exhibit comparable bioavailability to immediate-release solutions.
• Multiple-dose administration of these sustained-release formulations ensures near-complete time coverage within the therapeutic range.
• These formulations are effective in maintaining therapeutic theophylline plasma levels, exceeding minimum thresholds for extended durations.