3) of ACEL(0.15) and ACEL(0.30) also suggested that both the proportions exhibited a singe step weight loss at about 200 °C. The X-ray powder diffraction patterns of ACT, ACEU and ACEL are shown in Fig. 4. Intense and sharp diffraction peaks at 9.9°, 21.8°, 24.9° and 29.5° 2θ and weak and diffused peaks at 16.5°, 17.3°, 18° and 23.6° 2θ; in addition to peaks at 20.3° and 20.9° 2θ in the diffraction pattern of ACT confirmed its crystalline polymorphic form A.12 ACT also showed additional diffused peak at 12.1° and an intense peak at 31.6° 2θ. Characteristic hump shaped diffraction pattern in the range of 10–20° 2θ for EPO confirmed
its amorphous nature, whereas a sharp and intense peak at 19.1° 2θ as well as a diffused and weak peak at 23.3° 2θ for POL confirmed its semi-crystalline nature. 1:2 proportion of ACEU could be differentiated from 1:1 proportion on the grounds that the principal peaks SCH727965 were observed with much lower intensity and significant broadening in 1:2 proportion and it
was assessed to provide relatively more extent of amorphisation. Amorphous character of ACT in ACEL was significantly improved by the addition of MI-773 concentration POL as evident by XRPD profiles. XRPD profile of ACEL(0.30) distinctly showed a halo diffraction pattern and absence of all the principal peaks corresponding to crystalline ACT, unlike that of ACEL(0.15), which confirmed that the drug was molecularly dispersed in the polymer–plasticiser matrix and the extrudates much so formed were homogeneous, amorphous solid solution.
Percent content of ACT in ACEU and ACEL was found to be in the range of 98.3 ± 0.16%–99.1 ± 0.23% (n = 3) of theoretical proportion of the drug in the respective solid dispersions. The intrinsic solubility and in vitro dissolution rate of ACT, ACEU and ACEL in 0.1 N HCl is shown in Table 1 and Fig. 5, respectively. As compared to pure drug, both the proportions of ACEU exhibited considerable enhancement in intrinsic solubility; with more than 90% drug release in about 60 min. This could be attributed to high mass transfer associated with increased surface area of the drug by the high shear during extrusion process. Furthermore, both the proportions of ACEL reported about 7–10 folds enhancement in intrinsic solubility and more than 90% drug release within ∼20 min. Such enhancement in solubility characteristics could be attributed to decreased recrystallisation of the drug within plasticised polymer and lack of strong intramoleular bonds within ACT and existence of week intermolecular hydrogen bonds between the drug and plasticised polymer molecules. These randomly arranged molecules required less energy to separate and dissolve as compared to crystalline ACT. In addition, poloxamer being non-ionic surfactant further improved wettability of the dispersed drug particles. The hydrophilic polyoxyethylene segment of the copolymer also prevented aggregation or agglomeration of individual drug particles, thus improving solid–liquid surface tension.