2.1.1. Phase Solubility Studies

The stoichiometry of the RSP/RM-β-CD inclusion complex and its stability constant were investigated by means of phase solubility studies. The phase solubility diagram of RSP with RM-β-CD was obtained at 25 ◦C by plotting the apparent equilibrium concentration of the drug against RM-β-CD concentration. The apparent solubility of RSP increased linearly (R<sup>2</sup> = 0.9980) as a function of RM-β-CD concentration in the 0–50 mM concentration range, as shown in Figure 2. The RSP solubility enhancement in phosphate buffer 0.1 M (pH 7.4) confirms the interaction between the drug substance and the CD. The linear relation between RSP concentration and RM-β-CD concentration indicates an *A<sup>L</sup>* type phase solubility diagram defined by Higuchi and Connors [38]; also, the slope value (0.1965) is less than unity, revealing that a soluble inclusion complex in 1:1 molar ratio was formed between the guest and host molecule in phosphate buffer 0.1 M (pH 7.4). The apparent stability constant (*K*1:1) of the inclusion complex calculated from the slope of the phase solubility diagram, using Equation (1) is 173.38 <sup>±</sup> 5.54 M−<sup>1</sup> ; this value is within the range of 100 and 5000, which is considered ideal for the formation of an inclusion complex that may improve the bioavailability profile [39,40].

**Figure 2.** Phase solubility diagram of risperidone (RSP) in the presence of randomly methylated β-cyclodextrin (RM-β-CD) in phosphate buffer 0.1 M, pH 7.4, at 25 ◦C.
