Development of ivermectin orally disintegrating tablets using factorial design: In-vitro evaluation and in vivo absorption pattern in rats

Abstract

The objective of the present study was to develop orally disintegrating tablets (ODTs) containing ivermectin (IVM) using a Design of Experiments (DoE) approach. The ODTs were composed of a diluent, superdisintegrant, lubricant, glidant, and sweetening agent, and were produced through direct compression. The formulations (F1–F8) were assessed by DoE, and the most appropriate ones were developed as porous tablets (direct compression followed by sublimation), with previous incorporation of ammonium bicarbonate as sublimating agent (F9–F10). This study identified that the combination of mannitol and croscarmellose provides ODTs with appropriate critical quality attributes. Pre-compression analyses did not show any drug-excipient incompatibility. F9 was found to have the most favourable quality properties with a disintegration time of 16.9 s, hardness of 2.8 Kp, and proper friability. In vitro dissolution profiles indicated that porous ODTs exhibited better drug dissolution performance than non-porous ones. Additionally, F9 presented an excellent stability behaviour, and the preliminary in vivo assessment revealed that IVM was rapidly absorbed and recovered in the bloodstream for at least 25 h post-treatment in rats. In conclusion, the results of the study demonstrate successful development and characterization of IVM ODTs, which could potentially improve adherence to paediatric treatment and address orphan formulation requirements.