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.
Lo
Julian B
JB
Pfizer Global R&D, Groton Laboratories, Groton, CT 06340, USA. julian.b.lo@pfizer.com
Appel
Leah E
LE
Herbig
Scott M
SM
McCray
Scott B
SB
Thombre
Avinash G
AG
D000468:Alkalies / Q000737:chemistry; D017963:Azithromycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D005744:Gastric Acid / Q000502:physiology; D005745:Gastric Acidity Determination; D041981:Gastrointestinal Tract / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D017186:Titrimetry
D000468:Alkalies; D003692:Delayed-Action Preparations; D020442:Poloxamer; D017963:Azithromycin