High-dose Coenzyme Q10 oleogels designed for orphan therapy

EHRENHAUS MASOTTA, NATALIA; MARTINEFSKI M; HOCHT C; LUCANGIOLI S.; ROJAS, A.M; TRIPODI V

Congreso; Drug Discovery for Neglected Diseases International Congress 2018; 2018

Introduction: Recently, Coenzyme Q10 (CoQ10) was established by the FDA as an orphan drug and its therapeutic recommended dose increased significantly, reaching values up to 50 mg/kg/day. Patients with CoQ10 deficiency usually have swallowing difficulties, whereby the use of solid dosage forms is not the best option because they find them hard to swallow resulting in a lower adherence to the treatment.Objectives: In order to satisfy the high-level requirements in adult patients and offer them a more comfortable way of treatment, a new oral CoQ10 dosage form was developed and evaluated. As CoQ10 is practically insoluble in aqueous solutions because of its lipophilic nature, oleogels were proposed to dose CoQ10.Materials and methods: CoQ10 oleogels were prepared by its dissolution in medium-chain triglyceride (MCT) oil, using ethylcellulose for gelling and sorbitan monostearate (SMS) as surfactant. Physicochemical stability of oleogels was tested by their rheological properties, colorimetry, lipid oxidation, syneresis and remaining CoQ10 content during 12 months at 25.0°C.Pharmacokinetic profile was tested by a single-dose bioavailability study after oral intake of an oleogel containing 1g of CoQ10 and compared to the commercial capsule involving 7 healthy subjects.Results and discussion: Thermoreversible oleogels with a maximal amount of 1g of CoQ10 were developed with proved stability during at least 12 months of storage at 25.0°C. SMS allowed high stability to oxidation of the MCT-oil retained by the gel network, as well as low syneresis. Plastic deformation of oleogels without fracture was determined under compression, emulating the deformation behavior of the material into the oral cavity.