CHILD-IVITAB, a Novel Orodispersible Ivermectin Formulation - Pharmaceutical Evaluation and Clinical Acceptability in Children

Abstract

Background/Objectives: Scabies is a disease that disproportionately affects young children. Oral ivermectin is a mainstay of scabies therapy, yet children <15 kg are excluded due to insufficient safety data and the lack of age-appropriate formulations. To address this gap, we developed CHILD-IVITAB, a 1 mg ivermectin orodispersible tablet based on the Template Inverted Particle technology, which enables rapid disintegration and intrinsic taste masking in a mechanically robust tablet.

Methods: We report the pharmaceutical characterization of CHILD-IVITAB tablets. The EPIC-15 trial (NCT06404333) was a randomized clinical trial administering CHILD-IVITAB to children weighing 5 to <15 kg with uncomplicated scabies in Brazil. Acceptability was assessed at two administrations (D0, D7) using the ClinSearch Acceptability Score Test (CAST^®), wherein CHILD-IVITAB was compared to a reference dataset.

Results: The 40 mg tablets had a tensile strength of 1.87 ± 0.16 MPa, and met Ph. Eur. requirements for uniformity of mass and dosage units. CHILD-IVITAB tablets disintegrated in vitro in 18.3 ± 1.1 s and released >50% of the dose within 1 min in artificial saliva. Thirteen children were enrolled in the trial. The full dose was taken in 100% of the 26 evaluations, 73% of administrations elicited a neutral or positive reaction, and no dosage form alteration, food/drink co-administration, or extra device was required. The barycenter of all evaluations fell within the positive zone of the CAST^® framework.

Conclusions: These results support CHILD-IVITAB as a child-friendly ivermectin formulation suitable for children 5 to <15 kg, a population currently excluded from ivermectin treatment and prevention programs.

Introduction

Scabies is a skin infestation caused by the mite Sarcoptes scabiei. It is characterized by severe itching and is transmitted through prolonged direct skin-to-skin contact. Scabies is a major public health problem, especially in resource-poor populations, and was recognized as a neglected tropical disease (NTD) by the WHO in 2017 [1]. A systematic analysis of the Global Burden of Disease Study 2021 estimated a global incidence of 622.5 million cases and 5.3 million disability-adjusted-life years (DALYs), disproportionately affecting young children, with the highest incidence rate observed in children <5 years of age [2].

Ivermectin is a broad-spectrum antiparasitic drug known to be safe and effective in the treatment of scabies [3,4]. More than 400 million treatments are distributed annually by mass drug administration (MDA), with more than 6 billion treatments administered to date [5]. Despite the well-established safety profile of ivermectin in persons weighing more than 15 kg, ivermectin is currently not indicated for use in children weighing less than 15 kg due to insufficient safety data in this population [6].

Currently, the only commercially available oral ivermectin formulations are tablets designed for persons >15 kg that can readily swallow tablets. In children <15 kg, it is recommended that ivermectin tablets be crushed and suspended in liquid or mixed with food prior to administration [7], or given as a syrup [8]. The procedure of crushing and suspension is prone to imprecise dosing, loss of product during suspension, handling difficulties, and is not practical at scale for MDA. These limitations highlight the need for a child-friendly ivermectin formulation that ensures accurate dosing, intrinsic taste masking, acceptable palatability, stability in hot and humid environments, and suitability for use in both clinical and MDA settings. To address this need, a novel orodispersible tablet (ODT) formulation of ivermectin, called CHILD-IVITAB, has been developed. It is based on the Template Inverted Particle (TIP) technology, which consists of calcium phosphate microcapsules that serve as multifunctional drug carriers [9]. These TIP tablets offer a unique combination of hard tablets with rapid disintegration and enhanced taste masking. Their high internal porosity enables efficient loading of a wide range of drug substances, while the porous shell facilitates fast water uptake upon contact with saliva, resulting in in vitro disintegration times of less than 20 s [10]. This makes CHILD-IVITAB particularly suitable for pediatric patients, who commonly have difficulties swallowing conventional tablets. Dao et al. evaluated CHILD-IVITAB in a phase I crossover trial in 16 healthy adults and found enhanced palatability, good tolerability, and a more controlled absorption profile compared to standard ivermectin tablets (Stromectol®, MSD) [11]. Golhen et al. developed a population pharmacokinetic model, which indicated that a dose of 250 μg/kg CHILD-IVITAB in children <15 kg should achieve equivalent ivermectin exposure to the standard 200 μg/kg dose of STROMECTOL® in adults and children ≥15 kg [12].

In this paper, we report the pharmaceutical characterization and clinical acceptability of the 1 mg CHILD-IVITAB ODT that was administered to children weighing 5 to less than 15 kg with uncomplicated scabies in a phase IIb study conducted in Brazil. Acceptability, a prespecified secondary outcome, was formally evaluated in accordance with European Medicines Agency (EMA) recommendations for pediatric medicines [13,14], using the standardized ClinSearch Acceptability Score Test (CAST®) [15]. Tablet performance was assessed in terms of tensile strength, in vitro disintegration time, dissolution performance, uniformity of mass, and uniformity of dosage units.

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Materials

Ivermectin API was purchased from Pharmaserv (Stansstad, Switzerland). Citric acid monohydrate and ethanol were purchased from Hänseler (Herisau, Switzerland). Sodium croscarmellose was obtained from Spectrum (New Brunswick, NJ, USA). Rebaudioside A and peach aroma powder were purchased from Fontana (Canosa di Puglia, Italy). The microcapsule material (TIP) was manufactured at the Hospital Pharmacy in Basel according to the method described by Kost et al. [9].

The production of the study material took place under GMP at the Hospital Pharmacy in Basel, Switzerland. Ivermectin was dissolved in ethanol; the resulting solution was mixed with TIP powder and dried in an open container in a fume hood at room temperature for 24 h. Residual ethanol and moisture were controlled by loss on drying (<0.5%). This resulted in ivermectin-loaded TIP at a drug load of 2.8% (w/w), which was combined with citric acid monohydrate (5% w/w), croscarmellose sodium (3% w/w), rebaudioside A (2.5% w/w), and peach aroma powder (0.5% w/w) to obtain a final tablet with a target dose of 1 mg ivermectin. Taste masking was achieved by both incorporation of ivermectin within TIP microcapsules as well as addition of aroma.

The tablets were compacted using a STYL’One Evo (MEDELPHARM, Beynost, France) with 5 mm flat-faced tooling. The tablets had a target mass of 40 mg, containing 1 mg of ivermectin. In total, a batch of 950 tablets was produced and the uniformity of mass of all tablets was measured with a SADE SP-B60 checkweigher (CI Precision, Salisbury, UK). Tablets were packaged in 30 mL wide-mouth amber glass jars, 20 tablets per jar, closed with white tamper-evident screw caps. Tablets were stored at 15–30 °C

Aliu, D.; Vallet, T.; Huwyler, J.; Puchkov, M.; Pereira de Souza, L.; Freitas Medeiros, E.; Monteiro, W.; Sachett, J.d.A.G.; Ruiz, F.; Buettcher, M.; et al. CHILD-IVITAB, a Novel Orodispersible Ivermectin Formulation—Pharmaceutical Evaluation and Clinical Acceptability in Children <15 kg. Pharmaceutics 2026, 18, 1147. https://doi.org/10.3390/pharmaceutics18091147