QbD Approach for Novel Crosslinker-Free Ionotropic Gelation of Risedronate Sodium-Chitosan Nebulizable Microspheres:...

Area of Science:

• Pharmaceutical Sciences
• Biomaterials Engineering
• Drug Delivery Systems

Background:

• Risedronate sodium (RS) exhibits poor oral bioavailability and requires specific administration protocols to mitigate gastroesophageal side effects.
• Existing limitations necessitate alternative drug delivery strategies for enhanced efficacy and patient compliance in osteoporosis management.

Purpose of the Study:

• To develop novel, crosslinker-free, nebulizable risedronate-chitosan (RS-CS) microspheres using a Quality by Design (QbD) approach.
• To optimize formulation and process parameters for improved critical quality attributes including particle size, entrapment efficiency, and drug release.
• To evaluate the in vivo lung deposition and persistence of the developed microspheres.

Main Methods:

• Quality by Design (QbD) principles and risk assessment (RA) were employed to identify critical formulation and process parameters.
• Ishikawa diagrams and Plackett-Burman design were used for risk factor identification and screening.
• A multilevel factorial design optimized key parameters (RS:CS ratio, surfactant concentration, homogenization speed) to achieve desired microsphere characteristics.

Main Results:

• The optimized RS-CS microspheres (B6) exhibited a particle size of 3.47 ± 0.16 μm and high entrapment efficiency (94.58 ± 0.19%).
• Microspheres demonstrated a prolonged drug release profile over 12 hours (Q12h, 89.70 ± 0.64%) and positive surface charge (47.9 ± 3.39 mV).
• In vivo studies confirmed significant lung deposition (87 ± 3.54%) and sustained presence in rat lung tissues for 24 hours post-intratracheal instillation.

Conclusions:

• The QbD approach successfully facilitated the development of stable, nebulizable RS-CS microspheres with enhanced properties.
• The optimized microspheres offer a promising alternative for improved risedronate sodium delivery via inhalation, potentially enhancing osteoporosis treatment.
• This study highlights the efficacy of QbD in designing advanced drug delivery systems for pulmonary administration.