Impact of Solid Dispersions of Ivermectin on its Physical and Biopharmaceutical Properties

Congreso; 7 MA REUNIÓN INTERNACIONAL DE CIENCIAS FARMACÉUTICAS; 2023

Ivermectin is an antiparasitic drug with a broad spectrum of activity against ectoparasites and endoparasites. It is currently widely used to combat lymphatic filariasis and onchocerciasis, two neglected infectious diseases. However, it presents an unpredictable therapeutic response due to its low and erratic oral bioavailability linked to its poor aqueous solubility. Obtaining solid dispersions is an alternative that has been widely studied in the pharmaceutical field to improve the solubility of poorly soluble drugs. These systems are characterized by a better degree of wettability, a higher level of porosity, and reduced particle size, which increases the surface area, allowing rapid dissolution. Thus, the drug is available for rapid absorption upon contact with the gastrointestinal fluid. Solid dispersions can be classified according to the physical state of the vehicle in first, second, third, and fourth generations. Third generation incorporates polymers with surfactant properties or mixtures of amorphous polymers and surfactants. Its design seeks to achieve a greater increase in solubility compared to previous generations by enhancing its wettability. Poloxamer 407 is one of the most widely used polymers to obtain this type of dispersion. In this context, solid dispersions of Ivermectin with Poloxamer 407 in 1:1 and 1:2 w/w ratio were developed. In addition, the effect of the final cooling temperature on its properties was evaluated. These systems were characterized by Fourier Transform Infrared Spectroscopy, X-ray Powder Diffraction and Scanning Electron Microscopy. On the other hand, the effect of the mentioned systems on drug dissolution in simulated gastric fluid was examined. Furthermore, the dissolution profiles were analyzed using the similarity factor (f2), which is a measure for estimating the proximity between the in vitro dissolution profiles. The characterization studies revealed diffractograms of the solid dispersions that were the sum of the diffraction patterns of the individual components, which is a typical characteristic of this type of systems. Their infrared spectra showed intensity increases in different bands, that could be attributable to a hydrogen bonding interaction between the components. SEM images revealed that solid dispersions appear as compact blocks with mostly smooth surfaces, in contrast to physical mixtures that appear as fragments of the individual components. The results, on the other hand, demonstrated that these systems generated a higher dissolved percentage of ivermectin than the free drug and its physical mixtures. Also, according to the f2 values, the dissolution profiles of the systems obtained and their respective physical mixtures were not similar to the free drug curve. As a result, the absence of a new solid form was evidenced in this investigation, suggesting that the components of the developing systems interact through physical interactions. Furthermore, the ability of solid dispersions to improve the dissolution of ivermectin was established by preparing them with different proportions of components and different cooling conditions. In conclusion, these systems exhibited promising properties for the development of ivermectin oral pharmaceutical formulations.