Solubility, Polymorphism, Crystallinity, Crystal Habit, and Drying Scheme of (R, S)-(±)-Sodium Ibuprofen Dihydrate - Pharmaceutical Technology

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Solubility, Polymorphism, Crystallinity, Crystal Habit, and Drying Scheme of (R, S)-(±)-Sodium Ibuprofen Dihydrate
The racemic compound (R, S)-()-ibuprofen is a popular and well understood active pharmaceutical ingredient, but it has several disadvantageous formulation properties such as poor solubility, low melting point, and potential esterification with excipients containing an hydroxyl group. The authors investigate the use of an (R, S)-()-ibuprofen salt to evaluate these problems using various analytical methods to determine the polymorphism, crystallinity, and drying scheme.

Pharmaceutical Technology

Figure 5
When the positions of the 23 solvents were located within the 3-D space of a dispersion-force component (δd), a polar component (δp), and a hydrogen-bonding component (δh) according to their corresponding coordinates of (δd, δp, δh, ) in Table I and all the good solvents were represented by yellow and bad solvents by red in the form space (see Table III), a cluster of yellow domains were formed. The contour of these yellow domains outlined a 3-D volume of solubility in space. Good solvents were those solvents within the volume, bad solvents were solvents outside the volume (see Figure 5). This space could be represented by a solubility sphere with center coordinates (δd,API, δp,API, δh,API) and interaction radius (RS-API), for (R, S)-()-sodium ibuprofen dihydrate in the 3-D Hansen plot.

By trial and error, the center coordinates (δd,API, δp,API, δh,API) were determined using the following (15):

Figure 6
in which DS–API was the distance between the solvent location and the center of the sphere. For the 23 solvents listed in Table I with their corresponding sets of Hansen parameters (δd,s, δp,s, δh,s ), 23 DS–API would result for any chosen set of center coordinates (δd,API, δp,API, δh,API). Only one particular set of center coordinates of (δd,API, δp,API, δh,API) giving 9 DS–API values for nine corresponding good solvents that were < the 14 DS–API values calculated from the 14 bad solvents. The largest value among the nine DS–API values was the interaction radius of the solubility sphere. For (R, S)-()-sodium ibuprofen dihydrate at 25 C, the values of δd,API, δp,API, δh,API, and RS–API with respect to the 23 solvents listed in Table I were determined to be 19.89, 16.19, 30.89 and 25.92 MPa1/2, respectively (21, 22).


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