Predicting the Strength of Cohesive and Adhesive Interparticle Interactions for Dry Powder Inhalation Blends of Terbutaline Sulfate with α‑Lactose Monohydrate

Cai Y. Ma, Thai T. H. Nguyen, Parmesh Gajjar, Ioanna D. Styliari, Robert B. Hammond, Philip J. Withers, Darragh Murnane, Kevin J. Roberts

Research output: Contribution to journalArticlepeer-review

3 Downloads (Pure)

Abstract

Grid-based systematic search methods are used to investigate molecule–molecule, molecule–surface, and surface–surface contributions to interparticle interactions in order to identify the crystal faces that most strongly affect particle behavior during powder blend formulation and delivery processes. The model system comprises terbutaline sulfate (TBS) as an active pharmaceutical ingredient (API) and α-form lactose monohydrate (LMH). A combination of systematic molecular modeling and X-ray computed tomography (XCT) is used to determine not only the adhesive and cohesive interparticle energies but, also the agglomeration behavior during manufacturing and de-agglomeration behavior during delivery after inhalation. This is achieved through a detailed examination of the balance between the adhesive and cohesive energies with the XCT results confirming the blend segregation tendencies, through the particle–particle de-agglomeration process. The results reveal that the cohesive interaction energies of TBS–TBS are higher than the adhesive energies between TBS and LMH, but that the cohesive energies of LMH–LMH are the smallest between molecule and molecule, molecule and surface, and surface and surface. This shows how systematic grid-search molecular modeling along with XCT can guide the digital formulation design of inhalation powders in order to achieve optimum aerosolization and efficacy for inhaled medicines. This will lead to faster pharmaceutical design with less variability, higher quality, and enhanced performance.
Original languageEnglish
Pages (from-to)5019-5031
Number of pages13
JournalMolecular Pharmaceutics
Volume20
Issue number10
Early online date8 Sept 2023
DOIs
Publication statusE-pub ahead of print - 8 Sept 2023

Keywords

  • α-lactose monohydrate
  • X-ray computed tomography
  • powder inhalation formulations
  • interparticle interactions
  • molecular modeling
  • terbutaline sulfate

Fingerprint

Dive into the research topics of 'Predicting the Strength of Cohesive and Adhesive Interparticle Interactions for Dry Powder Inhalation Blends of Terbutaline Sulfate with α‑Lactose Monohydrate'. Together they form a unique fingerprint.

Cite this