Solubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipients


The aim of this study was to enhance the kinetic solubility and dissolution rate of ibuprofen by co-milling with different excipients and to establish the underlying mechanism(s) for such enhancement. In the first-part, two excipients (HPMC and soluplus) were selected from seven, and the optimal ball-milling parameters of speed and time (18 Hz, 15 min) were determined based on solubility-enhancement and flow-ability criteria. In the second-part, co-milling of different weight-ratios of ibuprofen-to-excipient was carried out and solubility and dissolution rates were determined. Mechanisms of biopharmaceutical enhancement were studied by SEM, laser diffraction, DSC, and FTIR analysis of the co-mixtures. Ibuprofen solubility (0.09 mg/mL for un-milled) was increased by factors of 4–5 and 10–20 for HPMC and soluplus, respectively. The weakening of crystals, stabilization of the amorphous phase and an increase in solid-state hydrogen bonding are the likely mechanisms for this enhancement. Reductions in Q70% dissolution time were also observed, by a factor of 4 and 7 for ibuprofen:HMPC and ibuprofen:soluplus co-milled mixtures, respectively. Although, there were similar reductions in particle size, dispersibility and degree of amorphization in both mixtures, the higher dissolution rate for soluplus, over that for HPMC, must be due to the additional solubilization contribution to the kinetic solubility provided by soluplus.


The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.


Poor soluble drugs, Ball milling, Solubility enhancement, Dissolution rate, Particle size, Amorphous content


Hussain, A., Smith, G., Khan, K.A., Bukhari, N.I., Pedge, N.I., Ermolina, I. (2018) Solubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipients. European Journal of Pharmaceutical Sciences. 123, pp. 395-403


Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)