Theophylline-loaded compritol microspheres prepared by ultrasound-assisted atomization

Nine solid dispersions were prepared by the melting method in the form of particles containing theophylline at 10%, 20%, and 30% (w/w) in three Compritols (Compritol 888 ATO, HD5 ATO, E ATO) to compare their efficiency in controlling theophylline release. After solidification the mass was ground and granules were evaluated by thermal [differential scanning calorimetry, hot stage microscopy (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, X-ray powder diffraction (XRD)] analysis and the solubility parameters. Another nine samples of the same composition were obtained as microspheres by ultrasound-assisted (US) atomization. XRD confirmed the presence of crystalline theophylline inside the solid dispersions. FTIR and Raman microspectroscopy revealed that crystals of the drug were present on the granule surface. On the contrary, the surface of the final microspheres did not present free drug crystals. The granules do not work so efficiently as microspheres in controlling the release of theophylline: 888 ATO ≈ HD5 ATO > E ATO represents the order of the ability of the Compritols to control the theophylline release from microspheres. HSM revealed that, on aging, the dissolved drug crystallizes, considerably modifying the granule formulation and that US vibration, speeding up the crystallization of the drug during the preparation of microspheres, greatly reduces the changes associated with aging.