Preparation of sustained release rifampicin microparticles for inhalation
Version of Record online: 9 JUL 2012
© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society
Journal of Pharmacy and Pharmacology
Themed Issue: Inhalation Pharmaceutics – Current Technologies and Approaches to Respiratory Drug Delivery. Guest Editors: Paul M. Young and Daniela Traini
Volume 64, Issue 9, pages 1291–1302, September 2012
How to Cite
Son, Y.-J. and McConville, J. T. (2012), Preparation of sustained release rifampicin microparticles for inhalation. Journal of Pharmacy and Pharmacology, 64: 1291–1302. doi: 10.1111/j.2042-7158.2012.01531.x
- Issue online: 6 AUG 2012
- Version of Record online: 9 JUL 2012
- Received December 9, 2011; Accepted March 26, 2012
- sustained release;
Objectives The aim of this research was to develop a novel carrier-free dry powder formulation of rifampicin for inhalation with controlled-release properties.
Methods Rifampicin dihydrate (RFDH) microcrystals were prepared by a polymorphic transformation of rifampicin. The prepared RFDH microcrystals were coated with poly (dl-lactide-co-glycolide) or poly (dl-lactide), using a spray-dryer equipped with two different types of three-fluid (3F) spray nozzles. The physicochemical and aerodynamic properties of the coated RFDH microcrystals were compared with those of conventional matrix microparticles.
Key findings The coated RFDH powder, encapsulating 50% of rifampicin, was successfully prepared by simple in-situ coating methods using two different types of 3F nozzles and had mass median aerodynamic diameter values of 3.5–4.5 µm. The thin flaky morphology of RFDH powders, providing good aerosolization properties, was maintained after coating. The coated RFDH formulations showed relatively low initial rifampicin release, compared with the uncoated RFDH crystals, followed by slow rifampicin release (about 70%) over 8 h in phosphate-buffered saline media (pH 7.4). Significant chemical degradations were not observed from the crystalline-structured RFDH formulations, while the amorphous-structured matrix formulations showed chemical degradation in six months.
Conclusions These polymer coated RFDH formulations may be a valuable alternative in the treatment of tuberculosis since the carrier-free formulation offers the benefit of delivering a maximum-potency formulation of the antibiotic directly to the site of infection, and long drug residence times may be achieved by the controlled release of the drug.