Formulation design and pharmaceutical development of a novel controlled release form of azithromycin for single-dose therapy.

Background: Azithromycin's long serum half-life (approximately 68 hours) allows for a short 5-day, 3-day, and now 1-day course therapy with a large 2-g dose. Although the single-dose, 1-day therapy offers the advantage of 100% patient compliance, tolerance of such large dose becomes an issue.

Methods: The dosage form discussed in this article employed a melt-congealing process to produce matrix microspheres with a 3-hour, first-order release. The vehicle blend included alkalizing agents to minimize GI side effects, minimize loss of bioavailability, and mask the bitter taste of azithromycin.

Results: Azithromycin microspheres are small (approximately 200 microm) with a narrow particle size distribution. Drug release was optimized by controlling the amount of dissolution enhancer in the microspheres and by the addition of proper amount of alkalizing agents in the vehicle blend. The final formulation was selected based on a balance between bioavailability and tolerability.

Conclusions: Drug release from the microspheres was shown to occur via diffusion through the larger pores formed by dissolution of azithromycin crystals and the smaller interconnected pores formed by dissolution of poloxamer. Several clinical studies have been conducted with the formulation to evaluate its pharmacokinetics and to demonstrate its safety and efficacy. The combined suspension formulation for a 2-g dose of azithromycin provided taste-masking and good tolerability.