Optimization, In Vitro, and In Silico Characterization of Theophylline Inhalable Powder Using Raffinose-Amino Acid...

Area of Science:

• Pharmaceutical Technology
• Drug Delivery Systems
• Respiratory Medicine

Background:

• Dry powder inhalation is a promising drug delivery route for respiratory diseases.
• Theophylline (TN) is a key therapeutic agent for asthma, but its delivery requires optimization.
• Enhancing the physicochemical and aerodynamic properties of TN is crucial for effective lung deposition.

Purpose of the Study:

• To develop inhalable co-spray-dried theophylline (TN) microparticles using raffinose-amino acid carriers.
• To improve the solubility, aerodynamic performance, and lung deposition of TN for asthma therapy.
• To evaluate the potential of these microparticles as carriers for dry powder inhaler (DPI) development.

Main Methods:

• Co-spray-drying of theophylline with raffinose-amino acid carriers (leucine, glycine, arginine).
• Comprehensive characterization including particle size, structural analysis (XRD, DSC), morphology (SEM), and solubility.
• In vitro and in silico aerodynamic assessments (MMAD, FPF, lung deposition) and dissolution/diffusion studies.

Main Results:

• Leucine and glycine carriers yielded optimal microparticles with desired aerodynamic properties (MMAD 4.6-5 µm, FPF 30.6-35.1%) and amorphous structures.
• Co-spray-dried TN exhibited enhanced solubility (~19-fold) and rapid in vitro release (~100% in 10 min).
• Formulations with leucine and leucine-glycine showed highest FPF (45.7-47.8%) and in silico lung deposition (39.3-40.1%). Arginine carriers were excluded due to poor performance.

Conclusions:

• The developed TN microparticles possess superior physicochemical, morphological, and aerodynamic characteristics.
• These microparticles demonstrate significant potential as carriers for low-dose theophylline dry powder inhalers for asthma treatment.
• The innovative formulation offers a promising approach for advancing respiratory drug delivery systems.