Formulation pre-screening of inhalation powders using computational atom-atom systematic search method.

Area of Science:

• Materials Science
• Pharmaceutical Science
• Computational Chemistry

Background:

• Synthonic modeling offers a molecule-centered understanding of crystal surface properties.
• This approach has been widely used to study crystallization processes.

Purpose of the Study:

• To evaluate the functional relevance of synthonic modeling in inhalation powder formulation.
• To assess the cohesivity of fluticasone propionate (FP), budesonide (Bud), salbutamol base (SB), and α-lactose monohydrate (LMH).

Main Methods:

• Synthonic modeling was employed to predict cohesive strengths of APIs and LMH.
• Cohesive strength measurements were performed using laser diffraction to determine the airflow pressure for complete dispersion (CPP).
• Aerosolization studies were conducted on FP-LMH blends.

Main Results:

• Synthonic modeling predicted FP to have higher cohesive strength than Bud or SB, correlating with CPP measurements.
• LMH exhibited the highest predicted cohesive strength, but its CPP value did not align with this prediction.
• High predicted adhesive forces between FP and LMH were observed, yet aerosolization showed FP agglomerates were not disrupted by LMH.

Conclusions:

• Synthonic engineering tools show potential for rapid pre-screening in drug formulation.
• Further understanding of hydrogen-bonded systems and agglomerate structure is needed for accurate modeling of excipients like LMH.
• The study highlights the applicability of synthonic modeling in pharmaceutical development while noting areas for refinement.