Single step spray drying method to develop proliposomes for inhalation: a systematic study based on quality by design...

Area of Science:

• Pharmaceutical Technology
• Drug Delivery Systems
• Quality by Design

Background:

• Pulmonary drug delivery requires precise formulation control for efficacy.
• Rifapentine is a key drug for tuberculosis treatment, necessitating improved delivery methods.
• Quality by Design (QbD) offers a systematic framework for developing robust pharmaceutical formulations.

Purpose of the Study:

• To apply Quality by Design (QbD) principles to develop rifapentine-loaded proliposomes for pulmonary inhalation.
• To optimize the spray drying method for single-step preparation of rifapentine proliposomes.
• To evaluate the in-vitro and in-vivo performance of the developed proliposomes.

Main Methods:

• Utilized a factorial design approach to optimize independent variables for proliposome preparation.
• Employed spray drying for single-step synthesis of rifapentine-loaded proliposomes.
• Assessed critical quality attributes including mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF).

Main Results:

• Optimized formulation (R-LDPI-7) achieved a respirable MMAD of 1.56 ± 0.16 μm and FPF of 92.5 ± 1.5%.
• Sustained rifapentine release followed Higuchi diffusion kinetics.
• Pulmonary pharmacokinetics showed a 7-fold increase in mean residence time and t1/2 in lungs compared to the control.

Conclusions:

• The study successfully demonstrated the application of QbD and Design of Experiments (DOE) for developing inhalation proliposomes.
• Spray-dried rifapentine proliposomes offer enhanced pulmonary retention and sustained release for tuberculosis therapy.
• This approach provides a robust method for creating advanced inhaled drug delivery systems.