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Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System
Published on: April 6, 2017
Formulation of rifampicin-cyclodextrin complexes for lung nebulization
Frédéric Tewes1, Julien Brillault, William Couet
1Inserm ERI-23, 40 avenue du recteur Pineau, 86022 Poitiers, France. ftewes@univ-poitiers.fr
Summary
Cyclodextrins (CDs) enhance rifampicin solubility and stability for nebulized lung delivery, improving pulmonary infection treatment. These complexes optimize rifampicin lung pharmacokinetics with effective antibacterial activity.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Pulmonary Medicine
Background:
- Nebulized antibiotics offer targeted lung delivery for pulmonary infections, minimizing systemic side effects.
- Poorly soluble drugs like rifampicin require formulation strategies for effective lung delivery.
- Cyclodextrins (CDs) can enhance solubility and bioavailability of poorly soluble drugs.
Purpose of the Study:
- To investigate rifampicin-cyclodextrin (CD) complexes for nebulized lung administration.
- To evaluate solubility enhancement, in vitro permeability, antibacterial activity, and nebulization characteristics of rifampicin-CD complexes.
Main Methods:
- Complexation efficiency and phase solubility diagrams of rifampicin with methylated beta-cyclodextrin (RAMEB) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were determined.
- Complex stability, in vitro permeability across Calu-3 cells, and antibacterial activity against Acinetobacter baumannii were assessed.
- Nebulization characteristics were evaluated using a NGI cascade impactor.
Main Results:
- Rifampicin-CD complexes significantly increased rifampicin apparent solubility (22-fold for RAMEB, 7.6-fold for HPbetaCD) at pH 9.
- Complexes showed satisfactory stability in physiological pH for 2 days and produced aerosol droplets suitable for pulmonary deposition.
- HPbetaCD complexation reduced the mass median aerodynamic diameter (MMAD) of aerosolized droplets; antibacterial activity was maintained.
Conclusions:
- Cyclodextrins effectively enhance rifampicin solubility and are suitable for nebulized lung delivery.
- Rifampicin-CD complexes optimize lung pharmacokinetic profiles and maintain antibacterial efficacy.
- CDs serve as promising vectors for improving rifampicin lung delivery and treatment of pulmonary infections.
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