Malays. J. Anal. Sci. Volume 29 Number 3 (2025): 1371

 

Research Article

 

Molecular insights: Aspirin-lactose monohydrate interactions for 3D-printed tablets via selective laser sintering

 

Nurul ‘Atiqah Hasrin1, Norzahir Sapawe1,*, Muhammad Farhan Hanafi1, Siti Nur’Aqilah Irwan1, and Siti Fatimah Ibrahim2

 

1Universiti Kuala Lumpur, Branch Campus Malaysian Institute of Chemical and Bioengineering Technology (UniKL MICET), Lot 1988 Vendor City, Alor Gajah, Melaka, Malaysia

2School of Chemical and Process Engineering, University of Leeds, LS2 9JT Leeds, United Kingdom.

 

*Corresponding author: norzahir@unikl.edu.my

 

Received: 29 September 2024; Revised: 6 May 2025; Accepted: 3 June 2025; Published: 29 June 2025

 

Abstract

Understanding the synthonic and surface energy properties of a drug molecule is essential for optimising the performance of formulated products, particularly in the pharmaceutical industry. However, gaining this insight often requires costly trial-and-error experiments. In this study, advanced surface analysis tools were introduced that provided visualisation and topological information based on crystallographic data. By using functional group analysis, roughness calculations, and statistical interaction data, direct comparisons of crystal surfaces were enabled. Molecular modelling simulations were conducted utilising Material Studio 7.0 software to evaluate the suitability of lactose (as an excipient) and aspirin (as an active pharmaceutical ingredient, API) crystals for the selective laser sintering (SLS) 3D-printing process. The study also examined each crystal’s morphology, lattice energy convergence, and contributions, such as interatomic and intermolecular interactions. These simulations offered preliminary insights into the potential compatibility of the selected compounds. Surface analysis of the aspirin and lactose crystal facets ranked their stability from strongest to weakest. For aspirin, the ranking was (1 0 0), (0 1 1), and (0 0 2), while for lactose, the order was (0 2 0), (0 0 1), and (0 1 1), indicating greater stability in the lactose facets. Theoretically, crystal faces with higher attachment and slice energies grow more rapidly and hold less morphological importance (MI), resulting in smaller surface areas. The stability of lactose monohydrate crystals may be linked to the presence of water molecules in their structure, which enhance the binding between the two substances. The study further demonstrates its practical relevance by correlating the sticking propensity of different aspirin and lactose surfaces with surface and particle descriptors derived from their single crystal structures. Interaction maps and surface roughness characteristics revealed that all three aspirin facets displayed hydrophobic behaviour, while the selected lactose facets exhibited hydrophilic properties, with a strong tendency for hydrogen bonding interactions due to the presence of hydrogen bond donors and acceptors.

 

Keywords: aspirin, lactose monohydrate, synthonic interaction, surface analysis, simulations

 

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