Related Experiment Video
Updated: Dec 20, 2025
Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals
Published on: March 30, 2017
Inhalable formulations of rifampicin by spray drying of supersaturated aqueous solutions
Kai Berkenfeld1, Jason T McConville2, Alf Lamprecht3
1University of Bonn, Institute of Pharmacy, Laboratory of Pharmaceutical Technology and Biopharmaceutics, Bonn, Germany.
Abstract:
Tuberculosis is still one of the leading causes of death from a single infectious agent (i.e. Mycobacterium tuberculosis). First line therapy includes per oral administration of high doses of rifampicin over several months and is often times accompanied by the occurrence of unwanted side effects that might limit the patient's adherence to the therapy. Thus, local antibiotic treatment at the site of infection i.e. the lungs is desirable. Amongst other approaches, spray drying of solutions of rifampicin has been shown as suitable method to produce respirable dry powders. In this work, we present inhalable formulations manufactured via spray drying of aqueous solutions of rifampicin. Powders manufactured were characterized for their aerodynamic and solid state properties, as well as their physical and chemical stability. The main focus of this study was to investigate the mechanism of particle formation using an acoustic levitator. Fine particle fractions of the test formulations ranged from 80 to 89% whereas a reference formulation (a spray dried isopropyl alcoholic solution of rifampicin) showed a lower fine particle fraction of 37%. Acoustic levitator and surface tension experiments showed that interfacial properties of rifampicin lead to early crust formation upon drying of the droplets, which eventually decoupled from the liquid core and formed highly collapsed, low apparent density powders with excellent aerosol properties.
Insights
Developing inhalable rifampicin dry powders via spray drying improves tuberculosis treatment. Aqueous formulations yield high fine particle fractions, overcoming side effects and enhancing patient adherence for effective lung delivery.
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Respiratory Medicine
Background:
- Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health threat.
- Current oral rifampicin therapy requires prolonged high-dose treatment, leading to side effects and poor patient adherence.
- Local delivery of antibiotics to the lungs is a promising strategy to improve TB treatment efficacy and tolerability.
Purpose of the Study:
- To develop inhalable dry powder formulations of rifampicin using spray drying of aqueous solutions.
- To characterize the aerodynamic, solid-state, and stability properties of the manufactured powders.
- To investigate the particle formation mechanism during spray drying using an acoustic levitator.
Main Methods:
- Spray drying of aqueous rifampicin solutions to produce inhalable dry powders.
- Aerodynamic particle size analysis to determine fine particle fraction (FPF).
- Solid-state characterization (e.g., crystallinity, morphology) and physical/chemical stability testing.
- Acoustic levitation to study droplet drying behavior and interfacial properties.
Main Results:
- Spray-dried aqueous rifampicin formulations achieved high FPFs ranging from 80-89%.
- These powders exhibited low apparent density and excellent aerosol properties due to particle collapse.
- Acoustic levitation revealed early crust formation driven by rifampicin's interfacial properties, leading to hollow particle structures.
- A reference formulation (spray-dried in isopropyl alcohol) showed a significantly lower FPF of 37%.
Conclusions:
- Spray drying of aqueous rifampicin solutions is a viable method for producing inhalable dry powders with superior aerosol performance.
- The unique particle formation mechanism, involving early crusting and collapse, is key to achieving high FPFs.
- These findings support the potential of inhaled rifampicin for localized lung delivery, offering an alternative to conventional oral therapy for tuberculosis.
More Related Videos
07:28Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System
Published on: April 6, 2017
04:59Author Spotlight: Developing a Disposable Dosator for Preclinical Testing of Dry Powder Inhalers in Small Animal Models
Published on: August 18, 2023
Related Concept Videos
01:23Inhaled Medications
01:22Drug Delivery: Miscellaneous Routes
Oral inhalation and nasal sprays swiftly transfer drugs across the respiratory epithelium's mucosal layer. Inhaled glucocorticoids and bronchodilators directly target lung conditions such as asthma, while fluticasone nasal spray mitigates allergic rhinitis.
Transdermal patches transport drugs...
01:18Additional Routes of Drug Administration
Administering drugs via inhalation allows for the direct delivery of gaseous, volatile substances or droplets to different parts of the respiratory tract. One of the advantages of the inhalation route is the rapid absorption of drugs into the circulatory system, which is possible because of the large surface area of...
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
01:17In Vitro Drug Dissolution: Alternative Methods
01:09In Vitro Drug Dissolution: Compendial Testing Models II