Physicochemical stability of solid dispersions of enantiomeric or racemic ibuprofen in stearic acid

Abstract

ABSTRACT:The aim of this study was to investigate the solid dispersion phase behavior of S-or RS-ibuprofen in stearic acid. By means of thermal analysis, we have demonstrated the total immiscibility, in solid state, of the corresponding binary mixtures. This indicates that no specific interactions exist between the chosen excipient and active pharmaceutical ingredient (API) that lead to eutectic systems. Furthermore, based on calorimetric and X-ray diffraction experiments, we have showed that upon cooling of the molten state, only stearic acid recrystallizes in the presence of S-ibuprofen, whereas a quaternary phase mixture is obtained for the racemic ibuprofen/stearic acid preparation. The solubility of stearic acid in S-ibuprofen liquid in all proportions was also determined. Overall, the results presented here offer an approach for the study of API/excipient interactions.

Prilling as manufacturing technique for multiparticulate lipid/PEG fixed-dose combinations

“…These findings were in agreement with Kobayashi (1988), who stated that only the thermostable C-form could be formed from a melt [31]. In contrast, Corvis et al (2011) reported recrystallization of stearic acid in the Eform from a ibuprofen/stearic acid melt. However, upon heating, this polymorph converted to the thermostable C-form at about 45 °C [32].…”

“…However, as no solid-solid transformations were detected prior to the melting endotherms of stearic and behenic acid (i.e. 68 and 75 °C, corresponding to the melting point of the C polymorph), it indicates that only the polymorph C was present in the formulations [32]. These findings were in agreement with Kobayashi (1988), who stated that only the thermostable C-form could be formed from a melt [31].…”

“…In contrast, Corvis et al (2011) reported recrystallization of stearic acid in the Eform from a ibuprofen/stearic acid melt. However, upon heating, this polymorph converted to the thermostable C-form at about 45 °C [32]. Thermal analysis of the physical mixtures and the formulations only revealed a melting endotherm of the fatty acids due to dissolution of the MPT crystals in molten stearic acid or behenic acid.…”

Overcoming the Solubility Barrier of Ibuprofen by the Rational Process Design of a Nanocrystal Formulation

“…In addition, although the said melting point of IBU is approximately 76 °C, formulations containing IBU and terfenadine are reported to melt at temperatures ranging from 50 to 76 °C [ 18 ]. This melting point depression is attributed to the tendency of IBU to form eutectic compositions, as has also been found for IBU mixtures with diphenhydramine hydrochloride, astemizole and stearic acid [ 19 ]. These compositions exhibit structural deteriorations such as crumbling, pitting and fissuring, as well as decolorization pertaining to the rise of instability and storage issues [ 18 ].…”

Interpretation of the global heat of melting in eutectic binary systems

“…from the baseline starting before the onset of the invariant peak to the baseline after the endset of the liquidus transformation. All the Q values presented in this work were calculated from published DSC profiles [7,11,[27][28][29].…”