Physicochemical Characterization of Interaction of Ibuprofen by Solid-State Milling with Aluminum Hydroxide

This present study is a preliminary exploration of the affinity between a carboxylic model drug ibuprofen and aluminum hydroxide. Ibuprofen was comilled with aluminum hydroxide in different weight ratios in the solid state and was characterized by scanning electron microscopy (SEM), X-ray powder diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. XRD and SEM studies indicated complete interaction of ibuprofen with aluminum hydroxide and complete amorphization of aluminum hydroxide–ibuprofen complexed salt as well, on comilling with aluminum hydroxide at 1:2 ratio. FTIR data showed the disappearance of acid carbonyl peak with the appearance and the corresponding increase in absorbance of new signal at 1,682 cm^?1 in the 1:1 and 1:2 ibuprofen–aluminum hydroxide-comilled powder. The accompanied increase in the absorbance of carboxylate peak in the ibuprofen–aluminum hydroxide physical mixture, and 1:0.1, 1:0.5, 1:1, and 1:2 (IBA_pm, and IB₁A_0.1, IB₁A_0.5, IB₁A₁, and IB₁A₂, respectively) comilled powder indicated an acid–base reaction between ibuprofen and aluminum hydroxide. On storage at 40°C and 75% relative humidity (RH) for 10 weeks, XRD study showed the absence of reversion to the crystalline state and FTIR data revealed continued increase of new signal at 1,682 cm^?1 relative to carboxylic acid peak and no reappearance of carboxylic acid peak. In vitro dissolution studies revealed that the percent release of ibuprofen from the aluminum hydroxide-comilled powder is in the following order: IB₁A₂ < IB₁A₁ < ibuprofen crystal < ibuprofen milled alone < IB₁A_0.1 < IB₁A_0.5. Aluminum metal cation might have interacted to form a complex through the carboxyl and carbonyl groups of ibuprofen. Improved dissolution of drug associated with IB₁A_0.1 and IB₁A_0.5 is because of the absence of a new signal at 1,682 cm^?1 and improved amorphization of the drug to some extent. Dissolution of drug affected in IB₁A₂ and IB₁A₁ may be because of the insoluble stable complex formation.