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

JUAN, CANDELA; RODRIGUEZ, DAIANA; CEBALLOS, LAURA; LANUSSE, CARLOS; GALLO, LOREANA; GONZALEZ VIDAL, NOELIA

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

EDITIONS SANTE

Año: 2023 vol. 87

1773-2247

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 (directcompression followed by sublimation), with previous incorporation of ammonium bicarbonate as sublimatingagent (F9–F10). This study identified that the combination of mannitol and croscarmellose provides ODTs withappropriate 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 betterdrug 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 bloodstreamfor at least 25 h post-treatment in rats. In conclusion, the results of the study demonstrate successful developmentand characterization of IVM ODTs, which could potentially improve adherence to paediatric treatment andaddress orphan formulation requirements.1. IntroductionThe World Health Organization (WHO) estimates that around 50% ofthe medicines prescribed for children are not commercially available inappropriate dosage forms [1]. Healthcare professionals are oftenrequired to manipulate an adult medicine to obtain suitable doses for achild, in a so-called “off-label” use, which increases the variability of theproduct, and could produce stability issues or instruction errors [2]. Inrelation, when a drug approved for use in children exists, as well as itsindication for a certain pathology, but an appropriate dosage form is notavailable, it is known as “orphan formulation” [3].The capability to swallow solid dosage forms in the paediatric populationis a factor of age and health status, with significant inter-patientdifferences. There may not be a unique formulation ideal for paediatricpatients of all ages