Nanosuspensions of a poorly soluble investigational molecule ODM-106: Impact of milling bead diameter and stabilizer concentration.

Aqueous solubility of a drug substance is an important attribute affecting oral bioavailability. Nanonization, particle size reduction to submicron level, is an elegant approach to improve drug solubility and dissolution by increasing the surface energy, which in turn necessitates the use of stabilizers. The purpose of this study was to develop a nanosuspension of a practically water-insoluble investigational molecule by nanomilling approach using wet media milling. A variety of polymeric and surface active excipients were tested for their wettability. A combination of hydroxypropyl methylcellulose and sodium lauryl sulfate (SLS) were selected as stabilizers on the bases of compatibility studies and efficient wettability behaviour in contact angle measurements (≈80˚). A factorial design set-up was used to study the effect of milling bead diameter and stabilizer concentration on the efficiency of particle size reduction. Nanonization outcome was different when milling beads of 0.5 mm and 1 mm diameter were used at different concentrations of the stabilizers, which demonstrated the complex nature of the whole system. Storage of the nanosuspensions under different temperature conditions resulted only in minor changes of the particle size fractions.

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.