Image analysis of lutrol/gelucire/olanzapine microspheres prepared by ultrasound-assisted spray congealing

Abstract

Nine systems were prepared containing Gelucire 50/13 and various amounts (9-18-36-45% w/w) of Lutrol F68 and F127 in the presence and in the absence of 10% w/w of olanzapine and formulated as a solid dispersion in the form of microspheres by ultrasound (US)-assisted spray congealing. Thermal analysis, using differential scanning calorimetry (DSC) and thermomicroscopy (HSM), suggested the presence of particles of reduced size of olanzapine precipitated inside the microspheres. The microspheres were also studied by means of electron microscopy (SEM) for their shape and aspect, by some image analysis parameters (fractal dimension) and using Energy-dispersive X-ray (X-EDS) and micro-Raman spectroscopy to qualitatively evaluate the composition of different points of the surface. The surface of the microspheres displayed a non-homogeneous distribution of the drug by the presence of wart-like protuberances, whose number increases as the Lutrol content of the systems increases. The same systems in the absence of US, obtained after cooling the molten mixtures, lack these structures and only a very few of them can be found. The blooming of the surface was hypothesized as related to crystallization or phase de-mixing or lipid component diffusion of the carrier mixture inside the cooling mass subjected to ultrasound vibration. Ultrasounds accelerate the physical changes concerning carriers and drug, outlining the importance of ultrasound to achieve stability for formulations of this type. The microspheres de-aggregate on contact with the dissolution medium and release the drug with a bimodal mode according to the Lutrol content.

Keywords: Fractal dimension; Gelucire 50/13; Image analysis; Lutrol F68/F127; Microspheres; Olanzapine; Solid dispersion; Surface blooming; Ultrasound-assisted spray congealing.