Limitations of high dose carrier based formulations

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Inhalation Technology

Background:

• Dry powder inhalers (DPIs) are crucial for delivering medications directly to the lungs.
• Optimizing the formulation of DPIs is essential for efficient drug delivery and therapeutic efficacy.
• Understanding particle behavior in higher-dosed formulations is key for product development.

Purpose of the Study:

• To investigate the impact of increasing active pharmaceutical ingredient (API) content on particle dispersion and aerosol performance in carrier-based DPI formulations.
• To evaluate how varying concentrations of beclomethasone dipropionate (BDP) affect the efficiency of a dry powder inhalable formulation.
• To utilize a custom DPI development rig for precise analysis.

Main Methods:

• Formulated five DPI blends with beclomethasone dipropionate (BDP) concentrations ranging from 1% to 30% (w/w).
• Characterized formulation and component morphology using scanning electron microscopy (SEM) and particle size via laser diffraction.
• Assessed aerosol performance using the British Pharmacopoeia Apparatus E (Next Generation Impactor) and analyzed API content with HPLC.

Main Results:

• Higher BDP concentrations resulted in increased agglomerate size and formation of dense BDP multi-layers on the lactose carrier.
• API within multi-layers dispersed as agglomerates, not primary particles, leading to reduced aerosol performance.
• Increased deposition of BDP in the induction port and pre-separator was observed with higher concentrations.

Conclusions:

• Aerosol performance of the DPI formulation decreases inversely proportionally with increasing BDP concentration.
• API deposition in the induction port and pre-separator correlates with the amount of micronized particles (BDP and composite carrier).
• Findings provide insights for developing and optimizing higher-dosed carrier-based DPI formulations.