Characterization and Prediction of the Non-Bonded Molecular Interactions between Racemic Ibuprofen and α-Lactose Monohydrate Crystals Produced from Melt Granulation and Slow Evaporation Crystallization

Zulfahmi Lukman(1), Nornizar Anuar(2*), Noor Fitrah Abu Bakar(3), Norazah Abdul Rahman(4)

(1) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(2) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(3) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(4) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(*) Corresponding Author


Granulation of racemic ibuprofen (±IBP) and α-lactose monohydrate (ALM) at a slightly lower (±IBP) melting point is an efficient method of binding the active pharmaceutical ingredients (API) and excipient in a binderless condition. However, the co-crystals may be formed from recrystallization of ±IBP on ALM. The objective of this study is to evaluate the tendency of co-crystal formation of granules (3:7 w/w ratio of ±IBP:ALM) by melt granulation process. Second, investigate the recovery of crystals from polyethylene glycol (PEG) 300 solutions containing ±IBP-ALM mixtures. Characterizations of the samples were performed using Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC) and Powder X-Ray Diffraction (PXRD) system of the ±IBP-ALM granules produced from melt crystallization and harvested crystals from PEG 300 solution which is produced using slow evaporation crystallization. Crystal analysis of solution containing ±IBP-ALM mixtures revealed that the crystals formed were not co-crystals. Molecular interactions assessment through binding prediction between ±IBP and ALM terminating surfaces was conducted using molecular modelling technique. The result showed that the favorable binding sites of ±IBP molecules were on the surfaces of (0-20), (1-10), (001) and (011) ALM crystals. Successful binding prediction by the attachment energy method has proven that the co-crystal formation between these molecules is theoretically possible.


surface chemistry; hydrogen bond; lattice energy; melt crystallization; binding prediction

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