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Phospholipid-based pyrazinamide spray-dried inhalable powders for treating tuberculosis
Basanth Babu Eedara1, Ian G Tucker1, Shyamal C Das1
1New Zealand's National School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, P.O. Box 56, Dunedin 9054, New Zealand.
Developing spray-dried powders with pyrazinamide and DPPC improves pulmonary drug delivery for tuberculosis treatment. High DPPC content enhanced aerosolization, showing potential for improved lung sterilization.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Pulmonary Medicine
Background:
- Sterilizing necrotic granulomas in tuberculosis (TB) is challenging with conventional oral or parenteral drug administration.
- Pulmonary drug delivery offers a promising strategy to increase antitubercular drug concentrations directly within lung granulomas.
Purpose of the Study:
- To develop spray-dried (SD) powders of pyrazinamide, an essential anti-TB drug, using specific excipients for enhanced pulmonary delivery.
- To optimize the formulation of SD powders containing pyrazinamide, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and other components for improved aerosolization.
Main Methods:
- Spray-drying of pyrazinamide powders with varying concentrations of DPPC (5%, 15%, 25% w/w) and L-leucine using a BUCHI B-290 Mini Spray-Dryer.
- Physicochemical characterization of the SD powders, including particle size distribution and residual moisture.
- Evaluation of aerosol dispersion performance using a Next Generation Impactor (NGI) to determine the fine particle fraction (FPF).
Main Results:
- All developed SD powders exhibited a narrow particle size distribution (1.29-4.26μm) and low residual moisture (<2%).
- Solid-state analysis revealed a polymorphic transformation of pyrazinamide from the α to the γ form during spray-drying.
- SD pyrazinamide without excipients (PDDL0) showed poor aerosolization (FPF 8.5±1.0%), while the formulation with 25% DPPC (PDDL3) demonstrated significantly improved aerosolization (FPF 73.2±4.0%).
Conclusions:
- Incorporation of DPPC, particularly at higher concentrations, substantially enhances the aerosolization properties of spray-dried pyrazinamide powders.
- The developed inhalation powders show potential for improving drug delivery to the deeper lung for tuberculosis treatment.
- Further investigation is required to fully assess the therapeutic efficacy of these optimized inhalation powders for pulmonary tuberculosis.
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